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409 results on '"Service de Transplantation"'

1. Reverse transcriptase multiplex ligation-dependent probe amplification in endomyocardial biopsies for the diagnosis of cardiac allograft rejection

Author: Philippe Ruminy, Romain Guillemain, Jean-Paul Duong Van Huyen, Jean-Luc Taupin, Pierre-Julien Viailly, Philippe Rouvier, Nicolas Adam, Sabine Pattier, Claire Toquet, Patrick Bruneval, Ahmad Abdel Sater, Guillaume Coutance, Fanny Drieux, Eric Epailly, Arnaud François, Marie-Pierre Chenard, Marion Rabant, Shaida Varnous, Alexandre Loupy, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Laboratoire d'anatomie pathologique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anatomie et Cytologie Pathologique [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Equipe Traitement de l'information en Biologie Santé (TIBS - LITIS), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), NANTES (NANTES - Ana Path), Centre hospitalier universitaire de Nantes (CHU Nantes), Equipe de Recherche sur les Rationalités Philosophiques et les Savoirs (ERRAPHIS), Université Toulouse - Jean Jaurès (UT2J), Service d'Anatomie Pathologique Générale, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service de Chirurgie Cardio-Vasculaire, CHU Strasbourg-Nouvel Hôpital Civil, Department of Chest Medicine, Mont-Godinne Hospital-Catholic University of Louvain de Mont-Godinne, Service de transplantation cardiaque [CHU Nantes], Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Transplantation Rénale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Laboratoire de Recherche en Imagerie : Méthodes d'imagerie des Échanges transcapillaires (LRI - EA4062), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CCSD, Accord Elsevier, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de pathologie [CHU Strasbourg], CHU Strasbourg, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), and Hopital Saint-Louis [AP-HP] (AP-HP)
Subjects: Adult, Graft Rejection, Male, musculoskeletal diseases, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pathology, Biopsy, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, 030230 surgery, Allograft Rejection, 03 medical and health sciences, 0302 clinical medicine, GNLY, medicine, molecular biology, Humans, Multiplex, Multiplex ligation-dependent probe amplification, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Heart transplantation, class prediction analysis, Transplantation, business.industry, Myocardium, CCL18, Histology, Middle Aged, Allografts, Reverse transcriptase, 3. Good health, [SDV] Life Sciences [q-bio], Cross-Sectional Studies, endomyocardial biopsy, histopathology, Heart Transplantation, RNA, Female, Surgery, Histopathology, Cardiology and Cardiovascular Medicine, business, Multiplex Polymerase Chain Reaction
Abstract: International audience; Background: Molecular biology has emerged as a potential companion to histology for the diagnosis of rejection after heart transplantation. Reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA) is a technique of targeted gene expression analysis suitable for formalin-fixed paraffin-embedded (FFPE) biopsies. Our aim was to assess RT-MLPA for the diagnosis of allograft rejection in heart transplantation.Methods: We performed a cross-sectional, case-control, multicenter study. After the selection of a 14-transcript panel (endothelial burden, Natural killer cells, interferon-γ pathway, effector T-cells, and antigen presentation), RT-MLPA was applied to 183 FFPE endomyocardial biopsies (EMB), randomized into a training (n = 113) and a validation (n = 70) series. A two-step class prediction analysis was developed (Linear prediction score-LPS1: rejection vs non-rejection; LPS2: antibody-mediated rejection [AMR] vs acute cellular rejection [ACR]). A study of the agreement between pathology and RT-MLPA was performed.Results: Overall, 48 ACR, 82 AMR, 5 mixed rejection, and 48 non-rejection EMBs were analyzed. Three molecular clusters were delineated by unsupervised hierarchical analysis (molecular non-rejection, ACR, and AMR). AMR was characterized by the high expression of CCL4, GNLY, FCGR3, CXCL11 and ACR by the high expression of CCL18 and ADAMdec. RT-MLPA and histopathology agreed in the final diagnosis in 82.2%, 67.7%, and 76.8% of the EMB in the test, validation, and overall cohort, respectively. Disagreement cases were more common in the case of histologic low-grade rejection and early post-transplant EMB.Conclusions: RT-MLPA is a suitable technique for targeted gene expression analysis on FFPE EMB with a good overall agreement with the histologic diagnosis of heart allograft rejection.
Published: 2020

2. Infection of ventricular assist device detected and monitored by 18F-FDG PET/CT

Author: David Morland, Renaud Guedec-Ghelfi, Yannick Lepers, Estelle Blanc-Autrant, Sébastien Dejust, Département de Médecine Nucléaire, Institut Jean Godinot, Service de Médecine Nucléaire et Service de Transplantation Cardiaque Adulte, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, Service de Transplantation Cardiaque Adulte, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, Laboratoire de Biophysique, UFR de Médecine, Centre de Recherche en Sciences et Technologies de l'Information et de la Communication - EA 3804 (CRESTIC), and Université de Reims Champagne-Ardenne (URCA)
Subjects: Male, medicine.medical_specialty, Staphylococcus aureus, Prosthesis-Related Infections, medicine.medical_treatment, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 030204 cardiovascular system & hematology, Staphylococcal infections, 030218 nuclear medicine & medical imaging, Sepsis, 03 medical and health sciences, 0302 clinical medicine, Fluorodeoxyglucose F18, Positron Emission Tomography Computed Tomography, medicine, Humans, Radiology, Nuclear Medicine and imaging, Prosthesis-Related Infection, business.industry, General Medicine, Middle Aged, Staphylococcal Infections, medicine.disease, Treatment efficacy, 3. Good health, Homogeneous, Ventricular assist device, Fdg pet ct, Cutaneous inflammation, Radiology, Heart-Assist Devices, business
Abstract: International audience; We report a case of a 59-year-old man who presented with fever, sepsis, and left cervicothoracic cutaneous inflammation 13 months after implantation of Jarvik 2000 device. Device infection was suspected and 18F-FDG PET/CT showed an intense and homogeneous uptake along driveline cable. Bacteriological local sample showed Staphylococcus aureus. After adapted antibiotherapy, control 18F-FDG PET/CT displays treatment efficacy with no residual uptake in driveline. 18F-FDG PET/CT could be an important tool for early noninvasive detection of left ventricular assist device infection and monitoring antibiotherapy response.
Published: 2017

3. Thymoglobulin Induction and Sirolimus Versus Tacrolimus in Kidney Transplant Recipients Receiving Mycophenolate Mofetil and Steroids

Author: Jean-Marc Chalopin, Yves Vanrenterghem, Lionel Rostaing, Bernard Bourbigot, François Berthoux, Daniel Abramovicz, Bernard Charpentier, Nicole Lefrançois, Michel Delahousse, Elisabeth Cassuto, Gérard Rifle, Denis Glotz, Philippe Lang, Service de Néphrologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de néphrologie, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de néphrologie et transplantation, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut francilien de recherche en néphrologie et transplantation, Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, Service de néphrologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service de Néphrologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Service de transplantation rénale, Hôpital Foch [Suresnes], Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service d'urologie, andrologie et transplantation rénale, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, Service de transplantation, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), and Saas, Philippe
Subjects: Male, 030232 urology & nephrology, 030230 surgery, MESH: Kidney Transplantation, MESH: Antibodies, Monoclonal, 0302 clinical medicine, MESH: Antilymphocyte Serum, MESH: Child, Child, Kidney transplantation, MESH: Treatment Outcome, MESH: Aged, MESH: Middle Aged, Calcineurin, Antibodies, Monoclonal, Middle Aged, 3. Good health, Treatment Outcome, Child, Preschool, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Steroids, MESH: Immunosuppressive Agents, MESH: Calcineurin, Immunosuppressive Agents, Glomerular Filtration Rate, medicine.drug, Adult, medicine.medical_specialty, Adolescent, [SDV.IMM] Life Sciences [q-bio]/Immunology, Calcineurin Inhibitors, Urology, Renal function, Tacrolimus, Mycophenolic acid, 03 medical and health sciences, MESH: Tacrolimus, medicine, Humans, Aged, Antilymphocyte Serum, MESH: Mycophenolic Acid, Sirolimus, MESH: Adolescent, Transplantation, MESH: Humans, Thymoglobulin, business.industry, MESH: Child, Preschool, MESH: Adult, Mycophenolic Acid, medicine.disease, Kidney Transplantation, MESH: Male, MESH: Steroids, MESH: Glomerular Filtration Rate, Immunology, MESH: Sirolimus, business, MESH: Female
Abstract: International audience; BACKGROUND: To define the role of mammalian target of rapamycin inhibitors in kidney transplantation, we compared efficacy and safety of two immunosuppressive regimens-a calcineurin inhibitor-free regimen with depletive induction versus a calcineurin inhibitor-based regimen. METHODS: De novo renal allograft recipients were randomized before transplantation to receive sirolimus (SRL; n=71, group A) or tacrolimus (n=70, group B). All patients received mycophenolate mofetil and corticosteroids. In group A, patients received rabbit antithymocyte globulin induction. In group B, antithymocyte globulin therapy could be given in case of delayed graft function. The estimated glomerular filtration rate (GFR) (Nankivell's formula) at month 12 was the primary endpoint. RESULTS: GFR showed no significant difference at month 12, with 56.1 in group A versus 58.4 mL/min/1.73 m in group B. In functioning grafts, renal function was significantly better in the SRL group, with higher GFR values at months 1, 2, 3, 6, and 9 (P
Published: 2010

4. Each additional hour of cold ischemia time significantly increases the risk of graft failure and mortality following renal transplantation

Author: Michèle Kessler, Christophe Legendre, Nassim Kamar, Fanny Buron, Henri Kreis, Lionel Rostaing, Marc Ladrière, Magali Giral, Etienne Dantan, Amina Blidi, Emmanuel Morelon, Agnes Debout, Alexandra Poignas, Georges Mourad, Jean-Paul Soulillou, Yohann Foucher, Katy Trébern-Launay, Valérie Garrigue, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Biostatistique, Pharmacoépidémiologie et Mesures Subjectives en Santé, PRES Université Nantes Angers Le Mans (UNAM), Service de Transplantation Rénale et de Soins Intensifs [Hôpital Necker - APHP], Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Service de Néphrologie, Dialyse et Transplantation (Hôpital Lapeyronie [Montpellier] CHU), Hôpital Lapeyronie [Montpellier] (CHU), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Département de Néphrologie et Transplantation d'organes, Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Service de Transplantation Rénale [CHU Brabois], Centre Hospitalier Universitaire de Nancy (CHU Nancy), CIC biothérapies CBT 0503 [Nantes], Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Le Bihan, Sylvie
Subjects: Adult, Male, medicine.medical_specialty, Graft failure, Time Factors, 030232 urology & nephrology, graft survival, kidney transplantation, 030230 surgery, Cold Ischemia Time, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, patient survival, Risk Factors, Internal medicine, medicine, Humans, Prospective Studies, Treatment Failure, Kidney transplantation, Aged, Proportional Hazards Models, Kidney, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Proportional hazards model, business.industry, Hazard ratio, Cold Ischemia, Middle Aged, medicine.disease, Survival Analysis, Surgery, cold ischemia time, Transplantation, medicine.anatomical_structure, Nephrology, Cohort, Cardiology, Female, France, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Although cold ischemia time has been widely studied in renal transplantation area, there is no consensus on its precise relationship with the transplantation outcomes. To study this, we sampled data from 3839 adult recipients of a first heart-beating deceased donor kidney transplanted between 2000 and 2011 within the French observational multicentric prospective DIVAT cohort. A Cox model was used to assess the relationship between cold ischemia time and death-censored graft survival or patient survival by using piecewise log-linear function. There was a significant proportional increase in the risk of graft failure for each additional hour of cold ischemia time (hazard ratio, 1.013). As an example, a patient who received a kidney with a cold ischemia time of 30 h presented a risk of graft failure near 40% higher than a patient with a cold ischemia time of 6 h. Moreover, we found that the risk of death also proportionally increased for each additional hour of cold ischemia time (hazard ratio, 1.018). Thus, every additional hour of cold ischemia time must be taken into account in order to increase graft and patient survival. These findings are of practical clinical interest, as cold ischemia time is among one of the main modifiable pre-transplantation risk factors that can be minimized by improved management of the peri-transplantation period.
Published: 2015

5. A personalized follow-up of kidney transplant recipients using video conferencing based on a 1-year scoring system predictive of long term graft failure (TELEGRAFT study): protocol for a randomized controlled trial

Author: Angélique Bonnaud-Antignac, Christophe Legendre, Magali Giral, Sabrina Chailan, Sandra Gaboriau, Emmanuel Morelon, Aurélie Meurette, Emmanuelle Papuchon, Philippe Tessier, Jean-Benoit Hardouin, Yohann Foucher, Pascal Daguin, Karine Neau, Biostatistique, Pharmacoépidémiologie et Mesures Subjectives en Santé, PRES Université Nantes Angers Le Mans (UNAM), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Délégation à la recherche clinique et à l'innovation [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Transplantation Rénale et de Soins Intensifs [Hôpital Necker - APHP], Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Réseau CENTAURE [CHU Nantes] (Fondation, Centre d’Investigation Clinique en Biothérapie), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut de Transplantation et de Recherche en Transplantation (ITUN - Institut Transplantation Urologie Néphroplogie*), This work was supported by a grant from the French Ministry of Health (PHRC, PROG/20-12, 2011). The protocol was also independently peer-reviewed by this institution. The Region 'Pays de la Loire' and the Regional Health Agency (ARS) also support the rental of the tablets and the equipment deployed in Nantes Universality hospital., and Le Bihan, Sylvie
Subjects: Nephrology, Graft Rejection, Male, medicine.medical_specialty, Telemedicine, Personalized follow-up, Randomzed clinical trial, medicine.medical_treatment, 030232 urology & nephrology, computer.software_genre, law.invention, Kidney transplantation, 03 medical and health sciences, Study Protocol, 0302 clinical medicine, Videoconferencing, Randomized controlled trial, law, Internal medicine, medicine, Humans, 030212 general & internal medicine, Intensive care medicine, Dialysis, Protocol (science), [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Video conferencing, Graft Survival, medicine.disease, 3. Good health, Term (time), surgical procedures, operative, Female, Randomized clinical trial, business, computer, Immunosuppressive Agents, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background: Numerous well-established clinical parameters are taken into consideration for the follow-up adaptation of kidney transplant recipients, but there are important disparities between countries, centres and clinicians. Therefore, novel scoring systems have been developed, for instance the Kidney Transplant Failure Score (KTFS) which aims to stratify patients according to their risk of return to dialysis. We hypothesize that the efficiency of the follow-up after one year post-transplantation can be improved by adapting it to the risk of graft failure defined by the KTFS estimation.Methods/design: We propose a phase IV, open label, randomized, multicentric and prospective study. The study is registered with the Clinical Trials Registry NCT01615900. 250 patients will be allocated to one of two arms: the eHealth program versus the standard of care at hospital. In the standard group, patients classified at low-risk (KTFS ≤ 4.17) will be scheduled 4 visits at hospital per year, whilst high-risk patients will visit hospital 6 times. In the eHealth group, patients classified at low-risk will be interviewed 3 times by video conferencing and once at hospital, whilst 6 visits at hospital and 6 video conferencing will be scheduled for high-risk patients. Discussion: The current study allows to scientifically evaluate the etiologic impact of a novel eHealth program. This is important to clarify the possible contribution of telemedicine in the improvement of medical follow-up. The proposed design based on 4 different subgroups can be interesting to evaluate other personalized medicine programs.
Published: 2015

6. Maintaining calcineurin inhibition after the diagnosis of post-transplant lymphoproliferative disorder improves renal graft survival

Author: David Michonneau, Laure-Hélène Noël, Caroline Suberbielle, Emmanuel Morelon, Olivier Thaunat, Christophe Legendre, Henri Kreis, Marie-France Mamzer-Bruneel, Jean-Emmanuel Serre, Valérie Dubois, Emmanuel Bachy, Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service de Transplantation Rénale et de Soins Intensifs [Hôpital Necker - APHP], Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Etablissement français du sang- Rhône-Alpes [Lyon], Service d'Immunologie et d'Histocompatibilité, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Graft Rejection, medicine.medical_treatment, 030232 urology & nephrology, 030230 surgery, Kidney, Gastroenterology, 0302 clinical medicine, Postoperative Complications, Risk Factors, hemic and lymphatic diseases, Child, Kidney transplantation, Calcineurin, Graft Survival, Immunosuppression, Middle Aged, Chemotherapy regimen, 3. Good health, medicine.anatomical_structure, surgical procedures, operative, Nephrology, Child, Preschool, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, France, Adult, medicine.medical_specialty, Adolescent, Calcineurin Inhibitors, Lymphoproliferative disorders, Post-transplant lymphoproliferative disorder, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, Preschool, Aged, Retrospective Studies, Immunosuppression Therapy, Chemotherapy, business.industry, Infant, medicine.disease, Kidney Transplantation, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Lymphoproliferative Disorders, Immunology, business
Abstract: International audience; Post-transplant lymphoproliferative disorder (PTLD) is an uncontrolled proliferation of transformed lymphocytes fostered by immunosuppression. In addition to chemotherapy, treatment of PTLD includes a reduction of maintenance immunosuppression. Patients with PTLD have an increased risk of graft loss, suggesting that reduced immunosuppression strategy needs to be optimized with regard to graft outcome. Here we retrospectively reviewed 101 cases involving PTLD to identify the risks associated with graft loss. During a median follow-up of 70 months, 39 patients died and 21 lost their graft. Multivariate analysis found that an eGFR under 30 ml/min per 1.73 m(2) at PTLD diagnosis, a biopsy-proven acute rejection episode following reduction of immunosuppression, and the absence of calcineurin inhibition in maintenance immunosuppression are independent risk factors for allograft loss. Neither the type of PTLD nor the chemotherapy regimen was predictive of allograft failure. Histological analysis of graft biopsies showed that maintaining calcineurin inhibition after the diagnosis of PTLD reduced the risk of developing de novo anti-HLA antibodies and humoral rejection. Remarkably, calcineurin inhibitor maintenance was neither associated with higher mortality nor with worse progression-free survival. Thus, maintaining calcineurin inhibition at a reduced dose after the diagnosis of PTLD seems safe and may improve renal graft outcome, possibly through better control of the recipient's humoral immune response.
Published: 2014

7. Influence of Anemia on Patient and Graft Survival After Renal Transplantation: results from the French DIVAT cohort

Author: I. Szwarc, Jean-Paul Soulillou, Christophe Legendre, Fanny Buron, Marc Ladrière, Lionel Rostaing, Emmanuel Morelon, Nassim Kamar, Henri Kreis, Valérie Garrigue, Pascal Daguin, Magali Giral, Michèle Kessler, Georges Mourad, Service de Néphrologie, Dialyse et Transplantation (Hôpital Lapeyronie [Montpellier] CHU), Hôpital Lapeyronie [Montpellier] (CHU), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Réseau CENTAURE [Nantes], Université de Nantes (UN)-Institut de Transplantation et de Recherche en Transplantation (ITUN - Institut Transplantation Urologie Néphroplogie*)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université Paris Descartes - Paris 5 (UPD5), Service de Transplantation Rénale et de Soins Intensifs [Hôpital Necker - APHP], Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de transplantation rénale [CHRU Nancy], Centre Hospitalier Universitaire de Nancy (CHU Nancy), Département de Néphrologie, dialyse et transplantation [Hôpital de Rangueil, Toulouse], Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Department of Nephrology, Transplantation and Clinic Immunology [Hospices civils de Lyon], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Le Bihan, Sylvie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Réseau CENTAURE, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Néphrologie - Immunologie Clinique [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-PRES Université de Toulouse, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Adult, Male, medicine.medical_specialty, Anemia, Renal function, urologic and male genital diseases, Cohort Studies, Hemoglobins, Postoperative Complications, Internal medicine, hemic and lymphatic diseases, medicine, Humans, Renal Insufficiency, Chronic, Intensive care medicine, Aged, Retrospective Studies, Transplantation, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Hazard ratio, Graft Survival, Retrospective cohort study, Middle Aged, medicine.disease, Kidney Transplantation, female genital diseases and pregnancy complications, 3. Good health, surgical procedures, operative, Cohort, Female, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Kidney disease, Cohort study
Abstract: International audience; Background and Objectives. Contradictory results are reported concerning the influence of anemia on patient and graft survival after renal transplantation. Assuming that level of renal function and anemia are strongly correlated, posttransplantation anemia (PTA) may have a different impact depending on the stage of chronic kidney disease (CKD).Methods. This study is a retrospective multicenter analysis using the DIVAT French database. The prevalence, risk factors, and influence of 12-month PTA (World Health Organization's definition) on patient and graft survival were analyzed according to CKD stage (Modification of Diet in Renal Disease equation).Results. The prevalence of 12-month PTA in our cohort of 4217 patients was 41.1%. Multivariate analysis demonstrated that worse renal function, donor age, period of transplantation, induction therapy, and mTOR inhibitors were significant risk factors for PTA. Posttransplantation anemia was a significant risk factor for all-cause mortality in CKD stages 1 to 2T (hazard ratio, 2.39; 95% confidence interval, 1.99Y4.40) and 3T (hazard ratio, 1.52; 95% confidence interval, 1.08Y2.15) and for cardiovascular mortality only on CKD stages 1T and 2T. In renal transplant recipients with CKD stages 4 to 5T, patient and graft survival were similar in patients with versus without anemia. Graft survival was not influenced by PTA, whatever the CKD stage.Conclusions. Posttransplantation anemia is associated with decreased patient survival only in CKD stages 1T, 2T, and 3T. Posttransplantation anemia has no influence on graft survival regardless of CKD stage.
Published: 2014

8. Renal function with delayed or immediate cyclosporine microemulsion in combination with enteric-coated mycophenolate sodium and steroids: results of follow up to 30 months post-transplant

Author: Mourad , Georges, Karras , Alexandre, Kamar , Nassim, Garrigue , Valérie, Legendre , Christophe, Lefrançois , Nicole, Charpentier , Bernard, Bourbigot , Bernard, Pouteil-Noble , Claire, Bayle , François, Lebranchu , Yvon, Mariat , Christophe, Le Meur , Yann, Kessler , Michèle, Moulin , Bruno, Ducloux , Didier, Delahousse , Michel, Lang , Philippe, Merville , Pierre, Chaouche-Teyara , Kamel, Rostaing , Lionel, Service de Pédiatrie spécialisée, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Service de néphrologie adultes [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, Service de transplantation, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service de néphrologie, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Greffes d'Epitheliums et Regulation de l'Activation Lymphocytaire, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Service de néphrologie et transplantation, Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Service de néphrologie, dialyse, aphérèses et transplantation, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Service de néphrologie et tranplantation, CHU Saint-Etienne-Hôpital nord, Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Néphrologie et Transplantation, CHU Strasbourg, Service d'urologie, andrologie et transplantation rénale, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de transplantation rénale, Hôpital Foch [Suresnes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Novartis France SAS, Novartis Pharma S.A.S., The French Myriade FR01 Study Group, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de néphrologie et immunologie clinique, Hôpital Bretonneau-Université de Tours-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Saas, Philippe, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Lapeyronie, CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ) -Hôpital de la Cavale Blanche - CHRU Brest ( CHU - BREST ), Hospices Civils de Lyon ( HCL ) -Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Hôpital Bretonneau-Université de Tours-CHRU Tours, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Service de Néphrologie et Urologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 )
Subjects: Male, Time Factors, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Male, MESH: Creatinine, MESH: Tablets, Enteric-Coated, Kidney, Kidney Function Tests, MESH: Cyclosporine, MESH: Kidney Transplantation, MESH : Cyclosporine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Humans, MESH : Middle Aged, MESH : Female, MESH : Immunosuppressive Agents, MESH: Middle Aged, MESH: Humans, MESH : Drug Therapy, Combination, MESH : Humans, MESH : Kidney Function Tests, MESH: Time Factors, MESH : Creatinine, MESH : Follow-Up Studies, MESH: Follow-Up Studies, MESH: Kidney, MESH : Tablets, Enteric-Coated, Middle Aged, Kidney Transplantation, MESH : Kidney, MESH: Male, MESH: Drug Therapy, Combination, MESH: Kidney Function Tests, Creatinine, Cyclosporine, MESH : Kidney Transplantation, [SDV.IMM]Life Sciences [q-bio]/Immunology, Drug Therapy, Combination, Female, Tablets, Enteric-Coated, MESH: Immunosuppressive Agents, MESH: Female, Immunosuppressive Agents, MESH : Time Factors, Follow-Up Studies
Abstract: International audience; BACKGROUND: In the multicenter, open-label Myriade study, renal transplant patients were randomized to early cyclosporine microemulsion (CsA-ME, day 0) or delayed CsA-ME (day 6) with enteric-coated mycophenolate sodium (EC-MPS), steroids and interleukin-2 receptor induction. One-yr results have been published previously. We now report the results of an extension study in which patients were followed up for a period of three yr post-transplant. METHODS: All patients completing the one-yr core study on-treatment were eligible to enter the extension study. RESULTS: Of the 203 patients, 153 completed the core trial on-treatment; 144 (94%) entered the extension study with a minimum follow-up of one yr (73 early CsA-ME, 71 delayed CsA-ME). In 75% of patients receiving EC-MPS during the extension, the recommended dose was administered (1440 mg/d). Median creatinine clearance remained constant (57 mL/min) at 12, 24 and 30 months post-transplant and was similar in the early and delayed CsA-ME groups as well as in subpopulations with or without delayed graft function. One patient in the early CsA-ME group died. No grafts were lost. The incidence of BPAR from time of transplant to the end of the extension study was 17% (24/139). Seven patients (5%) discontinued the extension study prematurely because of adverse events. CONCLUSION: These results suggest that a regimen of CsA-ME, EC-MPS and steroids results in excellent survival rates with stable renal function over a mean follow-up of 30 months. Immediate introduction of CsA-ME has no deleterious effect on long-term renal function, even among patients with delayed graft function.
Published: 2007

9. Childhood Langerhans cell histiocytosis with severe lung involvement: a nationwide cohort study

Author: Ralph Epaud, Chiara Sileo, Mohamed Barkaoui, Kamila Kebaili, Aurélie Portefaix, Jean-François Emile, Jean Eudes Piloquet, Jean-François Chateil, Solenne Le Louet, Abdellatif Tazi, Sébastien Héritier, Nathalie Aladjidi, Valeria Della Valle, Corinne Armari-Alla, Philippe B. Chastagner, Claire Galambrun, Gwenaël Lorillon, Jean Miron, Despina Moshous, Sylvain Renolleau, Julien Lejeune, Hubert Ducou Le Pointe, Emmanuelle Bugnet, Raphael Chiron, J. Donadieu, Anne Lambilliotte, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de pédiatrie, d'hématologie et d'oncologie [Hôpital de La Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL), Hôpital la Tronche, Service d'endocrinologie pédiatrique [CHU Lille], Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Haut-Lévêque [CHU Bordeaux], Service de Transplantation Rénale et de Soins Intensifs [Hôpital Necker - APHP], Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Intercommunal de Créteil (CHIC), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hopital Saint-Louis [AP-HP] (AP-HP), Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay
Subjects: Pediatrics, medicine.medical_specialty, medicine.medical_treatment, lcsh:Medicine, Vinblastine, Asymptomatic, law.invention, Cohort Studies, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, Langerhans cell histiocytosis, law, Intensive care, Medicine, Lung transplantation, Humans, Pharmacology (medical), Child, Lung, Genetics (clinical), Retrospective Studies, Childhood Langerhans Cell Histiocytosis, [SDV.GEN]Life Sciences [q-bio]/Genetics, Severe, business.industry, Research, lcsh:R, Infant, Retrospective cohort study, General Medicine, Pulmonary, medicine.disease, Intensive care unit, Childhood, 3. Good health, Histiocytosis, Langerhans-Cell, 030228 respiratory system, Pneumothorax, 030220 oncology & carcinogenesis, medicine.symptom, business
Abstract: BackgroundLung involvement in childhood Langerhans cell histiocytosis (LCH) is infrequent and rarely life threatening, but occasionally, severe presentations are observed.MethodsAmong 1482 children (ResultsThe median age was 1.3 years at the first ICU hospitalization. Of the 17 patients, 14 presented with lung involvement at the LCH diagnosis, and 7 patients (41%) had concomitant involvement of risk-organ (hematologic, spleen, or liver). Thirty-five ICU hospitalizations were analysed. Among these, 22 (63%) were secondary to a pneumothorax, 5 (14%) were associated with important cystic lesions without pneumothorax, and 8 (23%) included a diffuse micronodular lung infiltration in the context of multisystem disease.First-line vinblastine–corticosteroid combination therapy was administered to 16 patients; 12 patients required a second-line therapy (cladribine:n = 7; etoposide-aracytine:n = 3; targeted therapyn = 2). A total of 6 children (35%) died (repeated pneumothorax:n = 3; diffuse micronodular lung infiltration in the context of multisystem disease:n = 2; following lung transplantation:n = 1). For survivors, the median follow-up after ICU was 11.2 years. Among these, 9 patients remain asymptomatic despite abnormal chest imaging.ConclusionsSevere lung involvement is unusual in childhood LCH, but it is associated with high mortality. Treatment guidelines should be improved for this group of patients: viral infection prophylaxis and early administration of a new LCH therapy, such as targeted therapy.
Published: 2020

10. First-in-human use of a marine oxygen carrier (M101) for organ preservation: A safety and proof-of-principle study

Author: Le Meur, Yannick, Badet, Lionel, Essig, Marie, Thierry, Antoine, Büchler, Matthias, Drouin, Sarah, Deruelle, Charles, Morelon, Emmanuel, Pesteil, Francis, Delpech, Pierre-Olivier, Boutin, Jean-Michel, Renard, Felix, Barrou, Benoit, Delpech, Pierre‐Olivier, Boutin, Jean‐Michel, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service d'urologie [Hôpital Edouard-Herriot, CHU-HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Service de Néphrologie-Hémodialyse-Transplantation rénale [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Service d'Urologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHRU de Brest, service de chirurgie urologique et de la transplantation reinale (CHU - BREST - Urologie), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service de Chirurgie Thoracique et Vasculaire - Médecine vasculaire [CHU Limoges], Service d'urologie [CHU de Poitiers], Service d'urologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service d'Urologie [Poitiers], Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours-Hôpital Bretonneau
Subjects: medicine.medical_specialty, delayed graft function (DGF), Organ Preservation Solutions, 030232 urology & nephrology, Ischemia, Urology, Cold storage, Renal function, kidney transplantation/nephrology, 030230 surgery, Kidney, clinical research/practice, Cold Ischemia Time, Microcirculation, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Immunology and Allergy, organ transplantation in general, Pharmacology (medical), Adverse effect, Transplantation, Machine perfusion, business.industry, Graft Survival, clinical trial, Organ Preservation, medicine.disease, Kidney Transplantation, Thrombosis, Tissue Donors, 3. Good health, Oxygen, Perfusion, ischemia reperfusion injury (IRI), [SDV.IMM]Life Sciences [q-bio]/Immunology, business
Abstract: International audience; The medical device M101 is an extracellular hemoglobin featuring high oxygen-carrying capabilities. Preclinical studies demonstrated its safety as an additive to organ preservation solutions and its beneficial effect on ischemia/reperfusion injuries. OXYgen carrier for Organ Preservation (OXYOP) is a multicenter open-label study evaluating for the first time the safety of M101 added (1 g/L) to the preservation solution of one of two kidneys from the same donor. All adverse events (AEs) were analyzed by an independent data and safety monitoring board. Among the 58 donors, 38% were extended criteria donors. Grafts were preserved in cold storage (64%) or machine perfusion (36%) with a mean cold ischemia time (CIT) of 740 minutes. At 3 months, 490 AEs (41 serious) were reported, including two graft losses and two acute rejections (3.4%). No immunological, allergic, or prothrombotic effects were reported. Preimplantation and 3-month biopsies did not show thrombosis or altered microcirculation. Secondary efficacy end points showed less delayed graft function (DGF) and better renal function in the M101 group than in the contralateral kidneys. In the subgroup of grafts preserved in cold storage, Kaplan-Meier survival and Cox regression analysis showed beneficial effects on DGF independent of CIT (P = .048). This study confirms that M101 is safe and shows promising efficacy data.
Published: 2020

11. Temporal trends in living kidney donation in France between 2007 and 2017

Author: Nicolas Bouvier, Valérie Moal, Antoine Durrbach, Michel Delahousse, Julien Allard, Alexandre Hertig, Cyril Garrouste, Lionel Couzi, Lionel Rostaing, Claire Pouteil-Noble, Laetitia Albano, Christophe Legendre, Marc Hazzan, Mathias Büchler, Cécile Vigneau, Bruno Moulin, Lola Jacquemont, Luc Frimat, Christophe Mariat, Marie Alice Macher, Christiane Mousson, François Gaillard, Moglie Le Quintrec, Isabelle Etienne, Veena Roberts, Dimitri Titeca-Beauport, Nassim Kamar, Antoine Thierry, Didier Ducloux, Philippe Rieu, Philippe Grimbert, Maryvonne Hourmant, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de néphrologie, Hôpital Pasteur [Nice] (CHU), Laboratoire de Physiologie, Faculté de médecine Rangueil, Sciences Pour l'Oenologie (SPO), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Néphrologie-Dialyse-Transplantation [CHU Amiens-Picardie], CHU Amiens-Picardie, Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Service de transplantation rénale, Hôpital Foch [Suresnes], Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), U542, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, Service de néphrologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Service de Néphrologie et Transplantation, CHU Strasbourg, Service de néphrologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de néphrologie et transplantation, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire de Reims (CHU Reims), Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de néphrologie adultes [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD [Nouvelle-Calédonie])-Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Université de Franche-Comté (UFC), Santé publique : épidémiologie et qualité des soins-EA 2694 (CERIM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION )-Assistance Publique - Hôpitaux de Marseille (APHM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Montpellier 1 (UM1)-Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), and Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, Adolescent, 030232 urology & nephrology, Renal function, 030230 surgery, Body Mass Index, 03 medical and health sciences, Young Adult, 0302 clinical medicine, temporal trends, Risk Factors, Internal medicine, medicine, Living Donors, Humans, Registries, 2. Zero hunger, Transplantation, Kidney, business.industry, Incidence, Kidney donation, Middle Aged, medicine.disease, Obesity, Kidney Transplantation, living kidney donors, Young age, Increased risk, medicine.anatomical_structure, Nephrology, Donation, Tissue and Organ Harvesting, Kidney Failure, Chronic, Female, France, business, Body mass index, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Glomerular Filtration Rate
Abstract: Background Long-term studies have demonstrated a slight increased risk for end-stage renal disease (ESRD) for living kidney donors (LKD). In France, living kidney donation doubled within the past 10 years. We investigated the change in characteristics of LKD between 2007 and 2017 and the adequacy of follow-up. Methods Data were obtained from the national registry for LKD. We compared characteristics of LKD between two study periods: 2007–11 and 2012–17, and stratified donors by age and relation to recipient. We aggregated four characteristics associated with higher ESRD risk [young age, first-degree relation to recipient, obesity, low glomerular filtration rate (GFR) for age] in a single risk indicator ranging from 0 to 4. Results We included 3483 donors. The proportion of unrelated donors >56 years of age increased significantly. The proportion of related donors Conclusions An increase in living kidney donation in France does not seem to be associated with the selection of donors at higher risk of ESRD and the proportion of donors with adequate annual follow-up significantly increased.
Published: 2021

12. Disease progression in patients with the restrictive and mixed phenotype of Chronic Lung Allograft dysfunction-A retrospective analysis in five European centers to assess the feasibility of a therapeutic trial

Author: Jens Gottlieb, Geert M. Verleden, Michael Perchl, Christina Valtin, Alexander Vallee, Olivier Brugière, Carlos Bravo, Institut Català de la Salut, [Gottlieb J] Dept. of Respir. Medicine OE 6870, Hannover Medical School, Hannover, Germany. Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany. [Verleden GM] Dept Respir. Med, Lung Transplant Unit, University Hospital Gasthuisberg, Leuven, Belgium. [Perchl M] Department of Cardiology, Section for Lung transplantation, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. [Valtin C] Dept. of Respir. Medicine OE 6870, Hannover Medical School, Hannover, Germany. [Vallee A] Délégation à la Recherche Clinique et à l'Innovation, Hôpital Foch, Suresnes, France. [Brugière O] Service de Transplantation Pulmonaire et Centre de compétence de la Mucoviscidose, Hôpital Foch, Suresnes, France. [Bravo C] Servei de Pneumologia, Vall d'Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Graft Rejection, Male, Pulmonology, Cardiovascular Procedures, Pulmonary Function, Diagnostic Radiology, Medical Conditions, Medicine and Health Sciences, Respiratory Analysis, Surgical Procedures, Operative::Surgical Procedures, Operative::Transplantation::Organ Transplantation::Lung Transplantation [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], enfermedades respiratorias::enfermedades bronquiales::bronquitis::bronquiolitis::bronquiolitis obliterante [ENFERMEDADES], Respiratory System Procedures, Bronchiolitis Obliterans, Optical Properties, Multidisciplinary, Radiology and Imaging, Graft Survival, Bronquiolitis, Middle Aged, Allografts, Pulmonary Imaging, afecciones patológicas, signos y síntomas::procesos patológicos::atributos de la enfermedad::progresión de la enfermedad [ENFERMEDADES], Europe, Survival Rate, Bioassays and Physiological Analysis, Physical Sciences, Disease Progression, Medicine, Female, Lung Transplantation, Research Article, Adult, Opacity, Imaging Techniques, Heart-Lung Transplantation, Science, Materials Science, Material Properties, Bronquis - Malalties - Prognosi, Surgical and Invasive Medical Procedures, Interstitial Lung Diseases, Research and Analysis Methods, Respiratory Disorders, Diagnostic Medicine, Humans, Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Progression [DISEASES], Retrospective Studies, Transplantation, Respiratory Tract Diseases::Bronchial Diseases::Bronchitis::Bronchiolitis::Bronchiolitis Obliterans [DISEASES], Organ Transplantation, Pulmons - Trasplantació, Spirometry, Chronic Disease, Feasibility Studies, intervenciones quirúrgicas::intervenciones quirúrgicas::trasplante::trasplante de órganos::trasplante de pulmón [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Primary Graft Dysfunction
Abstract: BackgroundChronic Lung Allograft Dysfunction (CLAD) is a major obstacle for long term survival after lung transplantation (LTx). Besides Bronchiolitis Obliterans Syndrome, two other phenotypes of CLAD, restrictive allograft syndrome (RAS) and mixed phenotype, have been described. Trials to test in these conditions are desperately needed and analyzing natural outcome to plan such trials is essential.MethodsWe performed a retrospective analysis of functional outcome in bilateral LTx recipients with RAS and mixed phenotype, transplanted between 2009 and 2018 in five large European centers with follow- up spirometry up to 12 months after diagnosis. Based on these data, sample size and power calculations for randomized therapeutic trial was estimated using two imputation methods for missing values.ResultsSeventy patients were included (39 RAS and 31 mixed phenotype), median 3.1 years after LTx when CLAD was diagnosed. Eight, 13 and 25 patients died within 6, 9 and 12 months after diagnosis and a two patients underwent re-transplantation within 12 months leading to a graft survival of 89, 79 and 61% six, nine and 12 months after diagnosis, respectively. Observed FEV1decline was 451 ml at 6 months and stabilized at 9 and 12 months, while FVC showed continuous decline. Using two methods of imputation, a progressive further decline after 6 months for FEV1 was noted.ConclusionThe poor outcome of these two specific CLAD phenotypes suggests the urgent need for future therapeutic randomized trials. The number of missing values in a potential trial seems to be high and most frequently attributed to death. Survival may be used as an endpoint in clinical trials in these distinct phenotypes and imputation techniques are relevant if graft function is used as a surrogate of disease progression in future trials.
Published: 2021

13. Renal transplantation outcomes in obese patients: a French cohort-based study

Author: Y, Foucher, M, Lorent, L, Albano, S, Roux, V, Pernin, M, Le Quintrec, C, Legendre, F, Buron, E, Morelon, S, Girerd, M, Ladrière, D, Glotz, C, Lefaucher, C, Kerleau, J, Dantal, J, Branchereau, M, Giral, Jean-Emmanuel, Serre, MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Pasteur Hospital, Hôpital Lapeyronie [Montpellier] (CHU), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), RTRS « Centaure », Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service de Transplantation Rénale [CHU Brabois], Centre Hospitalier Universitaire de Nancy (CHU Nancy), Hôpital Lariboisière-Fernand-Widal [APHP], and Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques
Subjects: Nephrology, Adult, Male, medicine.medical_specialty, medicine.medical_treatment, 030232 urology & nephrology, 030230 surgery, lcsh:RC870-923, Cohort Studies, Post-transplant outcomes, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Obesity, Dialysis, Kidney transplantation, Aged, 2. Zero hunger, Proportional hazards model, business.industry, Graft Survival, Middle Aged, lcsh:Diseases of the genitourinary system. Urology, medicine.disease, Kidney Transplantation, 3. Good health, Treatment Outcome, Cohort, Kidney Failure, Chronic, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, France, business, Cohort study, Body mass index, Research Article
Abstract: BackgroundWhilst there are a number of publications comparing the relationship between body mass index (BMI) of kidney transplant recipients and graft/patient survival, no study has assessed this for a French patient cohort.MethodsIn this study, cause-specific Cox models were used to study patient and graft survival and several other time-to-event measures. Logistic regressions were performed to study surgical complications at 30 days post-transplantation as well as delayed graft function.ResultsAmong the 4691 included patients, 747 patients were considered obese with a BMI level greater than 30 kg/m2. We observed a higher mortality for obese recipients (HR = 1.37,p = 0.0086) and higher risks of serious bacterial infections (HR = 1.24,p = 0.0006) and cardiac complications (HR = 1.45,p p = 0.0666) and no significant increased risk of early surgical complications.ConclusionsWe showed that obesity increased the risk of death and serious bacterial infections and cardiac complications in obese French kidney transplant recipients. Further epidemiologic studies aiming to compare obese recipients versus obese candidates remaining on dialysis are needed to improve the guidelines for obese patient transplant allocation.
Published: 2020

14. Prognostic value for long-term graft survival of estimated glomerular filtration rate and proteinuria quantified at 3 months after kidney transplantation

Author: Georges Mourad, Sophie Girerd, Valérie Garrigue, Luc Frimat, Kevin Duarte, Magali Giral, Jacques Dantal, Michèle Kessler, Marc Ladrière, Fanny Buron, Clément Mottola, Emmanuel Morelon, Nicolas Girerd, Alice Aarnink, Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Laboratoire d'immunologie et d'histocompatibilité, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), RTRS « Centaure », Service de Néphrologie, Dialyse et Transplantation (Hôpital Lapeyronie [Montpellier] CHU), Hôpital Lapeyronie [Montpellier] (CHU), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), BOZEC, Erwan, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], and Hospices Civils de Lyon (HCL)
Subjects: medicine.medical_specialty, medicine.medical_treatment, 030232 urology & nephrology, Urology, graft survival, Renal function, kidney transplantation, 030230 surgery, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, delayed graft function, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine, AcademicSubjects/MED00340, Kidney transplantation, Dialysis, Transplantation, Creatinine, Proteinuria, Proportional hazards model, business.industry, creatinine, Original Articles, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, chemistry, Nephrology, ischaemia reperfusion injury, Graft survival, medicine.symptom, proteinuria, business, Validation cohort
Abstract: Background The estimated glomerular filtration rate (eGFR) measured at 1 year is the usual benchmark applied in kidney transplantation (KT). However, acting on earlier eGFR values could help in managing KT during the first post-operative year. We aimed to assess the prognostic value for long-term graft survival of the early (3 months) quantification of eGFR and proteinuria following KT. Methods The 3-, 6- and 12-month eGFR using the Modified Diet in Renal Disease equation (eGFRMDRD) was determined and proteinuria was measured in 754 patients who underwent their first KT between 2000 and 2010 (with a mean follow-up of 8.3 years) in our centre. Adjusted associations with graft survival were estimated using a multivariable Cox model. The predictive accuracy was estimated using the C-index and net reclassification index. These same analyses were measured in a multicentre validation cohort of 1936 patients. Results Both 3-month eGFRMDRD and proteinuria were independent predictors of return to dialysis (all P Conclusion The 3-month eGFR was a valuable predictor of the long-term return to dialysis whose predictive accuracy was not significantly less than that of the 12-month eGFR in multicentre cohorts totalling >2500 patients. Three-month outcomes may be useful in randomized controlled trials targeting early therapeutic interventions.
Published: 2020

15. Exposition to glucose-based peritoneal dialysis fluids exacerbates adipocyte lipolysis and glycogen storage in rat adipose cells

Author: Carmen Lab, Team3 Carmen, Christophe Soulage, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université de Lyon, CarMeN, laboratoire, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], and Hospices Civils de Lyon (HCL)
Subjects: glucose-based peritoneal dialysis fluid, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Adipose tissue, White adipose tissue, 030204 cardiovascular system & hematology, Peritoneal dialysis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, white adipose tissue, Dialysis Solutions, Adipocyte, Internal medicine, Adipocytes, Animals, Humans, Lipolysis, Medicine, Glycogen, business.industry, General Medicine, Rats, [SDV] Life Sciences [q-bio], Glucose, Endocrinology, Basal (medicine), chemistry, peritoneal dialysis, Nephrology, lipolysis, Mannitol, business, medicine.drug
Abstract: International audience; Glucose absorption during peritoneal dialysis (PD) is suspected to promote visceral fat accretion and weight gain in PD patients. The current study was designed to test the impact of glucose-based PD fluids on adipose cell lipolysis and glycogen content. Rat adipose cells, isolated from epididymal fat pad, were exposed to a 30 vol./70 vol. mixture of glucose-based dialysis solutions (containing 1.36% and 3.86% glucose, Physioneal 35®; Baxter) or Krebs-Henseleit buffer for 4 h. Adipose cells were further incubated with laboratory-made solutions containing 1.36% and 3.86% glucose or mannitol as an osmotic control. Baseline and noradrenaline-stimulated lipolysis was measured, and glycogen content assayed. The glucose-based commercial PD fluids as well as the laboratory-manufactured high glucose solutions exacerbated lipolysis in baseline and noradrenaline conditions and increased glycogen stores in adipose cells. Mannitol solutions (1.36% and 3.86%) used as an osmotic control did not produce such effects. This study provides the first evidence that glucose-based dialysis solutions increase basal as well as stimulated lipolysis in adipocytes, an effect that is directly attributable to high concentrations of glucose per se.
Published: 2020

16. Comparison of creatinine-based equations for estimating glomerular filtration rate in deceased donor renal transplant recipients

Author: Luciano da Silva, Selistre, Sandrine, Lemoine, Allyriane, Dantec, Fanny, Buron, Vandréa Carla, de Souza, Mariana, Bertoldo, Carlos Eduardo, Poli-de-Figueiredo, Thomas, Rimmelé, Olivier, Thaunat, Lionel, Badet, Emmanuel, Morelon, Antoine, Sicard, Laurence, Dubourg, Bodescot, Myriam, Néphrologie, Dialyse, Hypertension et Exploration Fonctionnelle Rénale [Lyon], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Universidade de Caxias do Sul, Hospital Geral de Caxias do Sul [Caxias do Sul, Brésil], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Transplantation, Néphrologie et Immunologie Clinique [Lyon], Pontifical Catholic University of Rio Grande do Sul (PUC-RS), Service d'anesthésie-réanimation [Lyon], Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Urologie et Transplantation [Lyon], Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique UMR 5305 (LBTI), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), In the study period, only the author L.S. benefited from a postdoctoral scholarship grant from the Brazilian government (CAPES Foundation, Ministry of Education of Brazil, grant number: 88881.156638/2017-01)., Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Pontifícia Universidade Católica do Rio Grande do Sul [Porto Alegre] (PUCRS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Physiology, Science, Immunology, Surgical and Invasive Medical Procedures, Biochemistry, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Urinary System Procedures, Transplantation Immunology, Chronic Kidney Disease, Medicine and Health Sciences, Renal Transplantation, Renal Diseases, Humans, Renal Insufficiency, Chronic, Aged, Nutrition, Renal Physiology, Transplantation, Biology and Life Sciences, Kidneys, Organ Transplantation, Renal System, Middle Aged, Kidney Transplantation, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Diet, ROC Curve, Nephrology, Area Under Curve, Creatinine, Medicine, Female, Clinical Immunology, Anatomy, Clinical Medicine, Algorithms, Biomarkers, Glomerular Filtration Rate, Research Article
Abstract: International audience; Background: Estimating glomerular filtration rate (GFR) is important for clinical management in kidney transplantation recipients (KTR). However, very few studies have evaluated the performance of the new GFR estimating equations (Lund-Malmö Revised-LMR, and Full Age Spectrum-FAS) in KTR.Methods: GFR was estimated (eGFR) using CKD-EPI, MDRD, LMR, and FAS equations and compared to GFR measurement (mGFR) by reference methods (inuline urinary and iohexol plasma clearance) in 395 deceased-donor KTR without corticosteroids. The equations performance was assessed using bias (mean difference of eGFR and mGFR), precision (standard deviation of the difference), accuracy (concordance correlation coefficient-CCC), and agreements (total deviation index-TDI). The area under receiver operating characteristic curves (ROC) and the likelihood ratio for a positive result were calculated.Results: In the total population, the performance of the CKD-EPI, MDRD and FAS equations was significantly lower than the LMR equation regarding the mean [95%CI] difference in bias (-2.0 [-4.0; -1.5] versus 9.0 [7.5; 10.0], 5.0 [3.5; 6.0] and 10.0 [8.5; 11.0] mL/min/1.73m2, P0.900), and LMR equation had the best ability to correctly predict KTR with mGFR
Published: 2020

17. Comparison of longitudinal quality of life outcomes in preemptive and dialyzed patients on waiting list for kidney transplantation

Author: Magali Giral, Myriam Blanchin, Jean-Benoit Hardouin, Emmanuel Morelon, Line Auneau-Enjalbert, Aurélie Meurette, Véronique Sébille, Elisabeth Cassuto, MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Plateforme de Méthodologie et Biostatistique, Direction de la Recherche [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Réseau CENTAURE [Nantes], Université de Nantes (UN)-Institut de Transplantation et de Recherche en Transplantation (ITUN - Institut Transplantation Urologie Néphroplogie*)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Département de Néphrologie - Hôpital Pasteur [Nice], Hôpital Pasteur [Nice] (CHU), Biostatistique, Recherche Clinique et Mesures Subjectives en Santé, Université de Nantes (UN), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut de Transplantation et de Recherche en Transplantation (ITUN - Institut Transplantation Urologie Néphroplogie*), and Le Bihan, Sylvie
Subjects: Adult, Male, Quality of life, Pediatrics, medicine.medical_specialty, Psychometrics, Waiting Lists, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, Emotions, Waiting list, Peritoneal dialysis, Kidney transplantation, 03 medical and health sciences, 0302 clinical medicine, Renal Dialysis, Surveys and Questionnaires, Medicine, Humans, Renal replacement therapy, education, Dialysis, education.field_of_study, business.industry, 030503 health policy & services, Public Health, Environmental and Occupational Health, Preemptive, Middle Aged, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Transplantation, 030220 oncology & carcinogenesis, Female, Hemodialysis, 0305 other medical science, business, Peritoneal Dialysis
Abstract: International audience; PURPOSE:The waiting list period for kidney transplantation can be lengthy and associated with a deteriorated health-related quality of life (HRQoL). It might also be experienced differently depending on the experience of renal replacement therapy (preemptive or dialyzed patients), and the type of dialysis. The main objective of this study is to measure and compare HRQoL changes in preemptive, hemodialysis (HD), and peritoneal dialysis (PD) patients during the waiting list period for kidney transplantation.METHODS:A sample of adult patients on kidney transplant waiting list from three French University Hospital centers was recruited. HRQoL was measured using the SF-36 and a specific questionnaire (ReTransQol), which were collected every 6 months before transplantation in preemptive, HD, and PD patients. Mixed-effects models taking into account time and possible confounding factors were used to compare HRQoL changes between the three groups.RESULTS:Preemptive (n = 230), HD (n = 177), and PD patients (n = 39) were enrolled. The renal replacement therapy modalities, time (time on waiting list and age at registration), and gender were associated with HRQoL changes. The HD and PD patients had a significantly lower perceived HRQoL on Role Physical, Social Functioning, and Role Emotional dimensions than the preemptive patients, with lower scores for PD compared to HD patients. The HRQoL scores of all patients were lower compared to the French general population for all dimensions.CONCLUSIONS:A better understanding of pre-transplantation patients' experience can help improving patient care with adapted educational programs and psychological support depending on the type of renal replacement therapy.
Published: 2019

18. Predictive Modeling of Tacrolimus Dose Requirement Based on High-Throughput Genetic Screening

Author: Pierre Laurent-Puig, L. Toullec, Isabelle Etienne, Gabriel Choukroun, Cécile Vigneau, B. Hurault de Ligny, Mathias Büchler, Anne-Elisabeth Heng, Jean-François Subra, Antoine Thierry, E. Thervet, Anastasia Yartseva, Bruno Moulin, Cécilia Damon, C. Legendre, Dany Anglicheau, A. Monnot, Marie-Anne Loriot, Nicolas Pallet, P Beaune, Mathilde Bateson, Margaux Luck, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Mécanismes physiologiques et conséquences des calcifications cardiovasculaires: rôle des remodelages cardiovasculaires et osseux, Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Néphrologie - Hémodialyses [CHU Clermont-Ferrand], Pôle RHEUNNIRS [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Néphrologie [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), aucun, AGAETIS, Service de Transplantation Rénale, affiliation inconnue, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service de néphrologie et immunologie clinique, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Domaines Océaniques (LDO), Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Observatoire des Sciences de l'Univers-Institut d'écologie et environnement-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement - Clermont Auvergne (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Science et Technologie du Lait et de l'Oeuf (STLO), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Néphrologie, Hôpital Gabriel Montpied, CHU de Clermont-Ferrand, Clermont-Ferrand, France, Centre National de la Recherche Scientifique (CNRS)-Institut d'écologie et environnement-Observatoire des Sciences de l'Univers-Université de Brest (UBO)-Institut national des sciences de l'Univers (INSU - CNRS), and Université de Tours-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Genetic Markers, Graft Rejection, 0301 basic medicine, Genotype, translational research/science, immunosuppression/immune modulation, Biology, clinical research/practice, Bioinformatics, Polymorphism, Single Nucleotide, 030226 pharmacology & pharmacy, Tacrolimus, ABCC8, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, genomics, Humans, Immunology and Allergy, genetics, Pharmacology (medical), Genetic Testing, Gene, Transplantation, Models, Statistical, Transporter, Kidney Transplantation, Transplant Recipients, High-Throughput Screening Assays, 3. Good health, immunosuppressive regimens, Molecular network, 030104 developmental biology, [SDV.TOX]Life Sciences [q-bio]/Toxicology, biology.protein, Tacrolimus Dose, pharmacology, Immunosuppressive Agents, Drug metabolism
Abstract: International audience; Any biochemical reaction underlying drug metabolism depends on individual gene-drug interactions and on groups of genes interacting together. Based on a high-throughput genetic approach, we sought to identify a set of covariant single-nucleotide polymorphisms predictive of interindividual tacrolimus (Tac) dose requirement variability. Tac blood concentrations (Tac C0 ) of 229 kidney transplant recipients were repeatedly monitored after transplantation over 3 mo. Given the high dimension of the genomic data in comparison to the low number of observations and the high multicolinearity among the variables (gene variants), we developed an original predictive approach that integrates an ensemble variable-selection strategy to reinforce the stability of the variable-selection process and multivariate modeling. Our predictive models explained up to 70% of total variability in Tac C0 per dose with a maximum of 44 gene variants (p-value
Published: 2017

19. Anti-Donor HLA Antibody Response After Pancreatic Islet Grafting: Characteristics, Risk Factors, and Impact on Graft Function

Author: Pouliquen, Eric, Baltzinger, P., Lemle, A., Chen, Chien-Chia, Parissiadis, A., Borot, S., Frimat, L., Girerd, S., Berney, T., Lablanche, S., Benhamou, P. Y., Morelon, E., Badet, L., Dubois, V., Kessler, L., Thaunat, Olivier, Network, Gragil, Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Endocrinologie - Diabète et Maladies Métaboliques, Hôpitaux Universitaires de Strasbourg, Etablissement Français du Sang - Grand Est (EFS - alsace strasbourg), Service de Diabétologie - Endocrinologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Department of Surgery, University of Geneva [Switzerland], Service d'Endocrinologie, Pôle Digidune, CHU Grenoble, Service d'Urologie et Chirurgie de la Transplantation, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Etablissement français du sang- Rhône-Alpes [Lyon], Université de Lyon, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Service de diabétologie - endocrinologie, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, CHU Strasbourg, Geneva University Hospital (HUG), Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée [2016-2019] (LBFA [2016-2019]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire [Grenoble] (CHU), Service d'urologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), EFS de Lyon, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Genève = University of Geneva (UNIGE)
Subjects: Graft Rejection, Male, antibody-mediated (ABMR) [rejection], [SDV]Life Sciences [q-bio], medicine.medical_treatment, Islets of Langerhans Transplantation, 030232 urology & nephrology, 030230 surgery, Postoperative Complications, 0302 clinical medicine, HLA Antigens, Risk Factors, Isoantibodies, Immunology and Allergy, Pharmacology (medical), Longitudinal Studies, ComputingMilieux_MISCELLANEOUS, Sensitization, geography.geographical_feature_category, ddc:617, biology, Graft Survival, Middle Aged, Prognosis, Islet, Tissue Donors, 3. Good health, medicine.anatomical_structure, Immunosuppressive drug, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Antibody, Type 1, Adult, Human leukocyte antigen, clinical research/practice, 03 medical and health sciences, Diabetes mellitus, Diabetes Mellitus, alloantibody, medicine, Humans, Retrospective Studies, Transplantation, geography, business.industry, islet transplantation, Insulin, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Transplant Recipients, body regions, rejection: antibody-mediated (ABMR), Immunology, biology.protein, business, Follow-Up Studies
Abstract: International audience; Pancreatic islet grafting restores endogenous insulin production in type 1 diabetic patients, but long-term outcomes remain disappointing as a result of immunological destruction of allogeneic islets. In solid organ transplantation, donor-specific anti-HLA antibodies (DSA) are the first cause of organ failure. This retrospective multicentric study aimed at providing in-depth characterization of DSA response after pancreatic islet grafting, identifying the risk factor for DSA generation and determining the impact of DSA on graft function. Forty-two pancreatic islet graft recipients from the Groupe Rhin-Rhône-Alpes-Genève pour la Greffe d'Ilots de Langerhans consortium were enrolled. Pre- and postgrafting sera were screened for the presence of DSA and their ability to activate complement. Prevalence of DSA was 25% at 3 years postgrafting. The risk of sensitization increased steeply after immunosuppressive drug withdrawal. DSA repertoire diversity correlated with the number of HLA and eplet mismatches. DSA titer was significantly lower from that observed in solid organ transplantation. No detected DSA bound the complement fraction C3d. Finally, in contrast with solid organ transplantation, DSA did not seem to negatively affect pancreatic islet graft survival. This might be due to the low DSA titers, specific features of IgG limiting their ability to activate the complement and/or the lack of allogenic endothelial targets in pancreatic islet grafts.
Published: 2017

20. Anti-Factor B and Anti-C3b Autoantibodies in C3 Glomerulopathy and Ig-Associated Membranoproliferative GN

Author: Marie Frimat, Georges Deschênes, Christophe Legendre, Alexandre Hertig, Dominique Bertrand, Jérôme Olagne, Bruno Moulin, Tim Ulinski, Véronique Frémeaux-Bacchi, Stéphane Burtey, Lubka T. Roumenina, Michel Delahousse, Sophie Chauvet, Moglie Le Quintrec, Maria Chiara Marinozzi, Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Etudes sur les Réformes, l'Humanisme et l'Age Classique (CERHAC), Institut d'Histoire de la Pensée Classique (IHPC), Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP, Service de Néphrologie Pédiatrique, Hôpital Robert Debré, Paris, Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de transplantation rénale, Hôpital Foch [Suresnes], Service de Néphrologie et Transplantation, CHU Strasbourg, Diabète de Type 1 : mécanismes et traitements immunologiques, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'immunologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), CHU Tenon [APHP], Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS), Service de Néphrologie Pédiatrique [Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)
Subjects: Adult, Male, 0301 basic medicine, Adolescent, Glomerulonephritis, Membranoproliferative, [SDV]Life Sciences [q-bio], Complement receptor 1, Complement factor B, Young Adult, 03 medical and health sciences, Clinical Research, Glomerulopathy, Humans, Medicine, complement, Child, ComputingMilieux_MISCELLANEOUS, Autoantibodies, Retrospective Studies, biology, business.industry, Autoantibody, General Medicine, Middle Aged, medicine.disease, C3-convertase, In vitro, 3. Good health, chronic glomerulonephritis, 030104 developmental biology, Nephrology, Immunoglobulin G, Complement C3b, Immunology, Alternative complement pathway, Female, biology.gene, business, Nephrotic syndrome, Complement Factor B, clinical immunology
Abstract: International audience; In C3 glomerulopathy (C3G), the alternative pathway of complement is frequently overactivated by autoantibodies that stabilize the C3 convertase C3bBb. Anti-C3b and anti-factor B (anti-FB) IgG have been reported in three patients with C3G. We screened a cohort of 141 patients with C3G and Ig-associated membranoproliferative GN (Ig-MPGN) for anti-FB and anti-C3b autoantibodies using ELISA. We identified seven patients with anti-FB IgG, three patients with anti-C3b IgG, and five patients with anti-FB and anti-C3b IgG. Of these 15 patients, ten were diagnosed with Ig-MPGN. Among those patients with available data, 92% had a nephrotic syndrome, 64% had AKI, and 67% had a documented infection. Patients negative for anti-C3b and anti-FB IgG had much lower rates of infection (17 [25%] patients with C3G and one [10%] patient with Ig-MPGN). After 48 months, four of 15 (26%) positive patients had developed ESRD or died. All 15 patients had high plasma Bb levels, six (40%) patients had low levels of C3, and nine (60%) patients had high levels of soluble C5b9. In vitro, IgG purified from patients with anti-FB Abs selectively enhanced C3 convertase activity; IgG from patients with anti-C3b/anti-FB Abs enhanced C3 and C5 cleavage. IgG from patients with anti-C3b Abs stabilized C3bBb and perturbed C3b binding to complement receptor 1 but did not perturb binding to factor H. In conclusion, the prevalence of anti-C3b/anti-FB Abs and alternative pathway activation is similar in Ig-MPGN and C3G, suggesting similar pathogenic mechanisms. Identification of the underlying defect in Ig-MPGN could lead to improved treatment.
Published: 2017

21. Exome sequencing in Hereditary Hypophosphatemic Rickets

Author: Gaisne, Raphaël, Figueres, Lucile, Houillier, Pascal, Vargas-Poussou, Rosa, Lemoine, Sandrine, Leman, Claire, Vince, Nicolas, Gourraud, Pierre-Antoine, Limou, Sophie, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Regenerative Medicine and Skeleton research lab (RMeS), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité des maladies rénales et métaboliques [Hôpital Européen Georges-Pompidou - APHP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Génétique [CHU HEGP], Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), École Centrale de Nantes (ECN), Regenerative Medicine and Skeleton (RMeS), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), and Le Bihan, Sylvie
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2019

22. Lack of impact of pre-emptive deceased-donor kidney transplantation on graft outcomes: a propensity score-based study

Author: Magali Giral, Marc Ladrière, Sophie Girerd, Christophe Legendre, Laetitia Albano, Fanny Buron, Denis Glotz, Valérie Garrigue, Florent Le Borgne, Emmanuel Morelon, Carmen Lefaucheur, Yohann Foucher, Georges Mourad, Elisabeth Cassuto, MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), IDBC/A2com [Pace, France], Réseau CENTAURE, Département de Néphrologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hospices Civils de Lyon (HCL), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de transplantation rénale [CHRU Nancy], Centre Hospitalier Universitaire de Nancy (CHU Nancy), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Hôpital Pasteur [Nice] (CHU), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Immunoregulation And Immunointervention in Transplantation and Autoimmunity (Team 4 - U1064 Inserm - CRTI), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Le Bihan, Sylvie, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Kidney Transplant Center [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Paris Descartes - Paris 5 (UPD5), Department of Nephrology, Transplantation and Clinic Immunology [Hospices civils de Lyon], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Service de Néphrologie, Dialyse et Transplantation (Hôpital Lapeyronie [Montpellier] CHU), Hôpital Lapeyronie [Montpellier] (CHU), Paris Translational Research Center for Organ Transplantation & Department of Nephrology and Transplantation, Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de néphrologie et transplantation rénale [Nice], and Université Paris Descartes - Paris 5 (UPD5)-Sorbonne Université (SU)-CHU Necker - Enfants Malades [AP-HP]
Subjects: Male, medicine.medical_specialty, Time Factors, Waiting Lists, medicine.medical_treatment, 030232 urology & nephrology, 030204 cardiovascular system & hematology, patient and graft survival, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 03 medical and health sciences, 0302 clinical medicine, Renal Dialysis, Risk Factors, Internal medicine, medicine, Humans, Renal replacement therapy, Prospective Studies, causal inference, Propensity Score, Dialysis, Kidney transplantation, Transplantation, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Graft Survival, pre-emptive kidney transplantation, Middle Aged, medicine.disease, Kidney Transplantation, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Tissue Donors, 3. Good health, Treatment Outcome, Nephrology, Cohort, Propensity score matching, Kidney Failure, Chronic, dialysis, Observational study, Female, observational study, Hemodialysis, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract: International audience; BACKGROUND: A significant number of studies have compared graft outcomes between patients with Pre-emptive Kidney Transplantation (PreKT) and patients on Dialysis before their Kidney Transplantation (DiaKT). These studies have suffered from the limitation that the DiaKT group is composed of all the dialysed patients, including those placed on a waiting list at the time of their first dialysis session. This seriously questions the comparability of these patients with those placed on the waiting list a long time before the need for renal replacement therapy. The aim of this study was to precisely evaluate the causal effect of PreKT from deceased donors.METHODS: Data were extracted from the multicentric French DIVAT (Données Informatisées et VAlidées en Transplantation) cohort. The DiaKT group was composed of patients placed on the waiting list with an initial intention of pre-emptive transplantation. Cause-specific Cox models with propensity scores (inverse probability weighting) were used to study the patient and graft outcomes.RESULTS: Among the 1138 included patients, 554 patients were in the PreKT group. The outcomes of the PreKT group were similar compared with the DiaKT group. In particular, the life expectancy with a functioning graft was 8.51 years [95% confidence interval (CI) 8.20-8.81] for the PreKT recipients versus 8.49 years (95% CI 8.15-8.84) for the DiaKT recipients.CONCLUSIONS: Our results challenge the utility of PreKTs from deceased donors, especially with regard to the consequential increase in the waiting list.
Published: 2019

23. Pollution et stress oxydant

Author: Anne Lejay, Bernard Geny, Anne-Laure Charles, Alain Meyer, Mitochondrie, stress oxydant et protection musculaire (MSP), Université de Strasbourg (UNISTRA), Service d'explorations fonctionnelles, CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de transplantation rénale, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 03 medical and health sciences, 0302 clinical medicine, [SDV]Life Sciences [q-bio], Immunology and Allergy, 030212 general & internal medicine, 010501 environmental sciences, 01 natural sciences, 0105 earth and related environmental sciences
Published: 2019

24. Highly Variable Sialylation Status of Donor-Specific Antibodies Does Not Impact Humoral Rejection Outcomes

Author: Thomas Barba, Jean Harb, Stéphanie Ducreux, Alice Koenig, Virginie Mathias, Maud Rabeyrin, Eric Pouliquen, Antoine Sicard, Dimitri Chartoire, Emilie Dugast, Thierry Defrance, Emmanuel Morelon, Sophie Brouard, Valérie Dubois, Olivier Thaunat, Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biochimie, Université de Nantes (UN), Immunoregulation And Immunointervention in Transplantation and Autoimmunity (Team 4 - U1064 Inserm - CRTI), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Service de transplantation, néphrologie et immunologie clinique, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Service de pathologie, Hospices Civils de Lyon (HCL), HCL, INSERM, Subvention Transplantation et Thérapie cellulaire 2018 FRM, the Fondation CENTAURE, Etablissement Français du Sang and the Société Francophone d’Histocompatibilité et d’Immunogénétique., ANR-16-CE17-0007,PETTAR,Ciblage de PECAM-1 pour la prévention et le traitement du rejet humoral en transplantation d'organe(2016), Le Bihan, Sylvie, Ciblage de PECAM-1 pour la prévention et le traitement du rejet humoral en transplantation d'organe - - PETTAR2016 - ANR-16-CE17-0007 - AAPG2016 - VALID, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Graft Rejection, Male, lcsh:Immunologic diseases. Allergy, 0301 basic medicine, glycosylation, medicine.drug_class, Immunology, Monoclonal antibody, DSA, sialylation, 03 medical and health sciences, 0302 clinical medicine, Agglutinin, Isoantibodies, Biopsy, medicine, Humans, Immunology and Allergy, Receptor, Complement Activation, solid organ transplantation, Original Research, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, medicine.diagnostic_test, business.industry, Donor specific antibodies, Middle Aged, N-Acetylneuraminic Acid, Tissue Donors, In vitro, Immunoglobulin Fc Fragments, Complement system, Killer Cells, Natural, carbohydrates (lipids), body regions, Log-rank test, 030104 developmental biology, Immunoglobulin G, antibody-mediated rejection, Female, lcsh:RC581-607, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract: International audience; Clinical outcome in antibody-mediated rejection (AMR) shows high inter-individual heterogeneity. Sialylation status of the Fc fragment of IgGs is variable, which could modulate their ability to bind to C1q and/or Fc receptors. In this translational study, we evaluated whether DSA sialylation influence AMR outcomes. Among 938 kidney transplant recipients for whom a graft biopsy was performed between 2004 and 2012 at Lyon University Hospitals, 69 fulfilled the diagnosis criteria for AMR and were enrolled. Sera banked at the time of the biopsy were screened for the presence of DSA by Luminex. The sialylation status of total IgG and DSA was quantified using Sambucus nigra agglutinin-based chromatography. All patients had similar levels of sialylation of serum IgGs (∼2%). In contrast, the proportion of sialylated DSA were highly variable (median = 9%; range = 0-100%), allowing to distribute the patients in two groups: high DSA sialylation (n = 44; 64%) and low DSA sialylation (n = 25; 36%). The two groups differed neither on the intensity of rejection lesions (C4d, ptc, and g; p > 0.05) nor on graft survival rates (Log rank test, p = 0.99). in vitro models confirmed the lack of impact of Fc sialylation on the ability of a monoclonal antibody to trigger classical complement cascade and activate NK cells. We conclude that DSA sialylation status is highly variable but has not impact on DSA pathogenicity and AMR outcome.
Published: 2019

25. Missing self triggers NK cell-mediated chronic vascular rejection of solid organ transplants

Author: Vannary Meas-Yedid, Sébastien Dussurgey, Thomas Barba, Emmanuel Morelon, Maud Rabeyrin, Romain Guillemain, Maud Racapé, Jean-Paul Duong-Van-Huyen, Valérie Dubois, Chien-Chia Chen, Antoine Marçais, Stéphanie Ducreux, Jean-Christophe Olivo-Marin, Maarten Naesens, Jean-Luc Taupin, Antoine Sicard, Antonino Nicoletti, Olivier Thaunat, Patrick Bruneval, Béatrice Charreau, Helena Paidassi, Alice Koenig, Virginie Mathias, Alexandre Loupy, Thierry Walzer, Thierry Defrance, Jasper Callemeyn, Paidassi, Helena, Instituts Hospitalo-Universitaires B - Organ ProtEction and ReplAcement - - OPeRa2010 - ANR-10-IBHU-0004 - IBHU - VALID, Phenotypage pour le cancer - - PHENOCAN2011 - ANR-11-EQPX-0035 - EQPX - VALID, Ciblage de PECAM-1 pour la prévention et le traitement du rejet humoral en transplantation d'organe - - PETTAR2016 - ANR-16-CE17-0007 - AAPG2016 - VALID, Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Réponse immunitaire innée dans les maladies infectieuses et auto-immunes – Innate immunity in infectious and autoimmune diseases, Laboratoire HLA [EFS - Auvergne-Rhônes-Alpes], Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Departement de Pathologie [Hospices civils de Lyon], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), SFR Biosciences, Analyse d'images biologiques - Biological Image Analysis (BIA), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'immunologie, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), O.T. is supported by the Agence nationale pour la Recherche (ANR-16-CE17-0007-01), the Fondation pour la Recherche médicale (PME20180639518), and the Etablissement français du Sang. C.-C.C., E.M. and O.T. are supported by the Institut Hospitalo-Universitaire–Organ Protection and Replacement (IHU-OPeRa, ANR-10-IBHU-004). A.K. is supported by INSERM (poste accueil 2015/1239/BT), the Hospices Civils de Lyon and the Fondation du Rein. SFR Biosciences is supported by the Agence nationale pour la Recherche (ANR -11-EQPX-0035 PHENOCAN). E.M. and O.T. are members of the CENTAURE Transplantation Research Network., We thank Christelle Forcet and Violaine Tribollet for help with Xcelligence experiments, and Marie-Claude Gagnieu and Laurent Genestier for fruitful scientific discussions. The authors thank Mathilde Koenig for her contribution to the design of the figure., ANR-10-IBHU-0004,OPeRa,Organ ProtEction and ReplAcement(2010), ANR-11-EQPX-0035,PHENOCAN,Phenotypage pour le cancer(2011), ANR-16-CE17-0007,PETTAR,Ciblage de PECAM-1 pour la prévention et le traitement du rejet humoral en transplantation d'organe(2016), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Graft Rejection, 0301 basic medicine, Cell, Translational immunology, General Physics and Astronomy, Inflammatory diseases, 030230 surgery, 0302 clinical medicine, Receptors, KIR, lcsh:Science, Receptor, Cells, Cultured, Mice, Knockout, Multidisciplinary, medicine.diagnostic_test, biology, Tissue Donors, 3. Good health, Killer Cells, Natural, medicine.anatomical_structure, [SDV.IMM]Life Sciences [q-bio]/Immunology, Antibody, [SDV.IMM] Life Sciences [q-bio]/Immunology, Science, Human leukocyte antigen, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Biopsy, Homologous chromosome, medicine, Animals, Humans, Transplantation, Homologous, Inflammation, business.industry, Endothelial Cells, General Chemistry, Innate immune cells, Mice, Inbred C57BL, Transplantation, 030104 developmental biology, Microvessels, Immunology, biology.protein, Heart Transplantation, lcsh:Q, K562 Cells, beta 2-Microglobulin, business, K562 cells
Abstract: Current doctrine is that microvascular inflammation (MVI) triggered by a transplant -recipient antibody response against alloantigens (antibody-mediated rejection) is the main cause of graft failure. Here, we show that histological lesions are not mediated by antibodies in approximately half the participants in a cohort of 129 renal recipients with MVI on graft biopsy. Genetic analysis of these patients shows a higher prevalence of mismatches between donor HLA I and recipient inhibitory killer cell immunoglobulin-like receptors (KIRs). Human in vitro models and transplantation of β2-microglobulin-deficient hearts into wild-type mice demonstrates that the inability of graft endothelial cells to provide HLA I-mediated inhibitory signals to recipient circulating NK cells triggers their activation, which in turn promotes endothelial damage. Missing self-induced NK cell activation is mTORC1-dependent and the mTOR inhibitor rapamycin can prevent the development of this type of chronic vascular rejection., ‘Missing self’ is a mode of natural killer (NK) cell activation aimed to detect the lack of HLA-I molecules on infected or neoplastic cells. Here, the authors show that mismatch between donor HLA-I and cognate receptors on recipient NK cells mediates microvascular inflammation-associated graft rejection, a pathology that is preventable by mTOR inhibition.
Published: 2019

26. Natural killer cell infiltration is discriminative for antibody-mediated rejection and predicts outcome after kidney transplantation

Author: Dirk Kuypers, Evelyne Lerut, Pierre Marquet, Henriette de Loor, Wilfried Gwinner, Marie Essig, Stéphane Gazut, Frans Schuit, Dany Anglicheau, Jasper Callemeyn, Carole Saison, Leentje Van Lommel, Saleh Yazdani, Olivier Thaunat, Max Wevers, Ben Sprangers, Lieven Thorrez, Alice Koenig, Maarten Naesens, Line Heylen, Laure-Hélène Noël, Department of Nephrology and Renal Transplantation, University Hospitals Leuven [Leuven]-Catholic University Leuven, Laboratoire d'analyse des données et d'intelligence des systèmes (LADIS), Département Métrologie Instrumentation & Information (DM2I), Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, University Hospitals Leuven [Leuven], Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Gene Expression Unit, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Hannover Medical School [Hannover] (MHH), Département de Néphrologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Project: 305499,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,BIOMARGIN(2013), Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ESSIG, Marie, and Biomarkers of renal graft injuries in kidney allograft recipients - BIOMARGIN - - EC:FP7:HEALTH2013-03-01 - 2017-02-28 - 305499 - VALID
Subjects: 0301 basic medicine, Graft Rejection, Male, Biopsy, Cell, 030232 urology & nephrology, Datasets as Topic, Kidney, Transcriptome, 0302 clinical medicine, Cytotoxic T cell, Kidney transplantation, Oligonucleotide Array Sequence Analysis, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], natural killer cells, Middle Aged, Allografts, Prognosis, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Killer Cells, Natural, medicine.anatomical_structure, Treatment Outcome, Nephrology, antibody-mediated rejection, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, Infiltration (medical), Adult, Cell type, kidney transplantation, survival, Antibodies, Natural killer cell, histology, 03 medical and health sciences, Young Adult, Immune system, Predictive Value of Tests, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, Aged, business.industry, Gene Expression Profiling, Computational Biology, kid- ney transplantation, medicine.disease, 030104 developmental biology, Case-Control Studies, Immunology, gene expression, Kidney Failure, Chronic, business, Biomarkers
Abstract: Despite partial elucidation of the pathophysiology of antibody-mediated rejection (ABMR) after kidney transplantation, it remains largely unclear which of the involved immune cell types determine disease activity and outcome. We used microarray transcriptomic data from a case-control study (n=95) to identify genes that are differentially expressed in ABMR. Given the co-occurrence of ABMR and T-cell-mediated rejection (TCMR), we built a bioinformatics pipeline to distinguish ABMR-specific mRNA markers. Differential expression of 503 unique genes was identified in ABMR, with significant enrichment of natural killer (NK) cell pathways. CIBERSORT (Cell type Identification By Estimating Relative Subsets Of known RNA Transcripts) deconvolution analysis was performed to elucidate the corresponding cell subtypes and showed increased NK cell infiltration in ABMR in comparison to TCMR and normal biopsies. Other leukocyte types (including monocytes/macrophages, CD4 and CD8 T cells, and dendritic cells) were increased in rejection, but could not discriminate ABMR from TCMR. Deconvolution-based estimation of NK cell infiltration was validated using computerized morphometry, and specifically associated with glomerulitis and peritubular capillaritis. In an external data set of kidney transplant biopsies, activated NK cell infiltration best predicted graft failure amongst all immune cell subtypes and even outperformed a histologic diagnosis of acute rejection. These data suggest that NK cells play a central role in the pathophysiology of ABMR and graft failure after kidney transplantation. ispartof: Kidney International vol:95 issue:1 pages:188-198 ispartof: location:United States status: published
Published: 2019

27. Chronic Rejection in Human Vascularized Composite Allotransplantation (Hand and Face Recipients)

Author: Olivier Thaunat, Sylvie Testelin, Lionel Badet, J. Kanitakis, Jean-Michel Dubernard, Bernard Devauchelle, Emmanuel Morelon, Aram Gazarian, Palmina Petruzzo, Clinique Dermatologique, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service d'Urologie et Chirurgie de la Transplantation, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Department of Medical Sciences, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Clinique du Parc, Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], CHU Amiens-Picardie, CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), and Département de chirurgie maxillofaciale et stomatologie [CHU d'Amiens-Picardie]
Subjects: Graft Rejection, Vascularized Composite Allotransplantation, Transplantation, medicine.medical_specialty, Graft acceptance, business.industry, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Immunosuppression, 030230 surgery, medicine.disease, Surgery, 03 medical and health sciences, 0302 clinical medicine, Vascular narrowing, Atrophy, Deep tissue, Chronic Disease, medicine, Humans, 030211 gastroenterology & hepatology, Composite tissue, business, Immune mechanisms
Abstract: International audience; Vascularized composite tissue allografts (VCA) have become a viable option to restore severely damaged parts of the body that cannot be repaired with conventional surgical techniques. Acute rejection develops frequently in the early postgraft period both in human and experimental VCA, but the possibility of human VCA to undergo chronic rejection (CR) remained initially unknown. The experience gained over the years shows that, similar to solid organ transplants (SOT), human VCA can also develop CR. Chronic rejection is clinically mostly apparent on the skin and targets preferentially skin and deep vessels, leading, as in SOT, to graft vasculopathy and often to graft loss. Dermal sclerosis and adnexal atrophy are additional features of CR. The pathogenetic immune mechanisms involved (cell-mediated versus humoral) remain incompletely known. The changes of CR can be detected with skin and deep tissue biopsies. Modern in vivo imaging tools can detect vascular narrowing and have the advantage of being noninvasive. However, the diagnosis and treatment of CR remain challenging, as several important questions remain to be answered: a more accurate definition of CR in VCA is needed to establish criteria allowing an accurate and early diagnosis. The pathogenetic mechanisms of CR need to be better understood to allow more efficacious treatment. Favoring/triggering factors of CR need to be better known so that they can be avoided. As in SOT, there is a need for efficient tolerance-inducing protocols that will favor graft acceptance and (ideally) circumvent the necessity of lifelong immunosuppression.
Published: 2016

28. Notch signaling mediates crosstalk between endothelial cells and macrophages via Dll4 and IL6 in cardiac microvascular inflammation

Author: Sylvain Pagie, Sabine Pattier, Angélique Pabois, Christian L. Laboisse, Béatrice Charreau, Steven Nedellec, Claire Toquet, Nathalie Gérard, Philippe Hulin, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Anatomie Pathologique [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre Hospitalier Universitaire G. R. Laennec (HGRL Saint-Herblain), Service de transplantation cardiaque [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Plateforme MicroPicell [Nantes], Université de Nantes (UN), The IHU-Cesti project is supported by Nantes Metropole and the Pays de la Loire Region. This study is also supported by the ‘‘Fondation Centaure' (RTRS) which supports a French transplantation research network. There is a fellowship from the ‘‘Ministère de l’ Enseignement Supérieur et de la Recherche'., ANR-10-IBHU-0005,CESTI (TSI-IHU),Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU)(2010), ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011), ANR-11-LABX-0070,TRANSPLANTEX,Nouveaux loci d'histocompatibilité/biomarqueurs en transplantation humaine: de la découverte à l'app(2011), Le Bihan, Sylvie, Instituts Hospitalo-Universitaires B - Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU) - - CESTI (TSI-IHU)2010 - ANR-10-IBHU-0005 - IBHU - VALID, Laboratoires d'excellence - Immunothérapies Grand Ouest - - IGO2011 - ANR-11-LABX-0016 - LABX - VALID, and Nouveaux loci d'histocompatibilité/biomarqueurs en transplantation humaine: de la découverte à l'app - - TRANSPLANTEX2011 - ANR-11-LABX-0070 - LABX - VALID
Subjects: Graft Rejection, Cardiac transplant, 0301 basic medicine, Cell signaling, Endothelium, Endothelial cells, Notch signaling pathway, Macrophage polarization, Cell Communication, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Notch signaling, Adaptor Proteins, Signal Transducing, Pharmacology, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, CD40, Receptors, Notch, biology, Interleukin-6, Macrophages, Monocyte, Calcium-Binding Proteins, Allografts, Coculture Techniques, 3. Good health, Transplantation, Endothelial stem cell, HEK293 Cells, 030104 developmental biology, medicine.anatomical_structure, Microvessels, Immunology, Leukocytes, Mononuclear, cardiovascular system, Cancer research, biology.protein, Heart Transplantation, Intercellular Signaling Peptides and Proteins, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Signal Transduction, 030215 immunology
Abstract: International audience; Although short-term outcomes have improved with modern era immunosuppression, little progress has been made in long-term graft survival in cardiac transplantation. Antibody-mediated rejection (AMR) is one of the leading causes of graft failure and contributes significantly to poor long-term outcomes. Endothelial cell (EC) injury, intravascular macrophage infiltrate and microvascular inflammation are the histological features of AMR. Nevertheless, mechanisms of AMR remain unclear and treatment is still limited. Here, we investigated the mechanisms underlying vascular and inflammatory cell network involved in AMR at endothelial and macrophage levels, using endomyocardial transplant biopsies and EC/monocyte cocultures. First, we found that AMR associates with changes in Notch signaling at endothelium/monocyte interface including loss of endothelial Notch4 and the acquisition of the Notch ligand Dll4 in both cell types. We showed that endothelial Dll4 induces macrophage polarization into a pro-inflammatory fate (CD40 high CD64 high CD200R low HLA-DR low CD11b low) eliciting the production of IL-6. Dll4 and IL-6 are both Notch-dependent and are required for macrophage polarization through selective down and upregulation of M2-and M1-type markers, respectively. Overall, these findings highlight the impact of the graft's endothelium on macrophage recruitment and differentiation upon AMR via Notch signaling. We identified Dll4 and IL-6 as coregulators of vascular inflammation in cardiac transplantation and as potential targets for immunotherapy.
Published: 2016

29. Clinicopathological Findings of Chronic Rejection in a Face Grafted Patient

Author: Fanny Buron, Emmanuel Morelon, Jean Baptiste Pialat, Palmina Petruzzo, Sylvie Testelin, Lionel Badet, Olivier Thaunat, Bernard Devauchelle, Jean Kanitakis, Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Department of Medical Sciences, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Département de Dermatologie [CH Lyon-Sud, Pierre-Bénite], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Département de chirurgie maxillofaciale et stomatologie [CHU d'Amiens-Picardie], CHU Amiens-Picardie, Service de Radiologie, Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Graft Rejection, Male, Pathology, medicine.medical_specialty, Erythema, Biopsy, medicine.medical_treatment, Asymptomatic, Vascularized Composite Allotransplantation, medicine, Humans, Hypopigmentation, Transplantation, Facial Transplantation, business.industry, Graft Survival, Immunosuppression, Allografts, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Tacrolimus, 3. Good health, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Chronic Disease, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.symptom, business, Immunosuppressive Agents
Abstract: International audience; BACKGROUND: Skin chronic rejection (CR) in vascularized composite allotransplantation has not been included in the Banff classification yet. We report a face-transplant patient who developed cutaneous clinicopathologic changes suggestive of CR. METHODS: The recipient was a 27-year-old man with severe disfigurement of the lower face due to a pyrotechnic explosion. He received a facial allograft, including mandible, cheeks, lips, and chin, in November 2009. Immunosuppression included antithymocyte globulins and bone-marrow infusion then steroids, tacrolimus, and mycophenolate mofetil. RESULTS: During the first posttransplant year the acute rejection episodes were characterized by reversible oedema and erythema of the graft. Subsequently, the patient developed primary asymptomatic Epstein-Barr virus (EBV) infection, followed by EBV+ B-cell lymphoma and hepatic EBV-associated posttransplant smooth muscle tumors; therefore, the immunosuppressive treatment was greatly reduced. Since the second posttransplant year, the allografted facial skin became progressively sclerotic and presented pigmented macules on a background of hypopigmentation and teleangiectasias, resulting in a poikilodermatous aspect. Skin biopsies showed epidermal atrophy, basal cell vacuolization, and diffuse dermal sclerosis in the absence of significant dermal cell infiltration. The dermal capillaries showed thickened walls and narrowed lumina, whereas the large vessels did not show significant alterations. Neither donor-specific antibodies nor vascular Cd4 deposits were detected.A dysfunction of the graft functions occurred. It was evidenced by a decrease in mouth opening and modification of some phonemes although lip closure was still possible allowing food intake. CONCLUSIONS: This is the first report suggestive of CR in a face allotransplantation after immunosuppression minimization.
Published: 2015

30. Performances of creatinine-based glomerular filtration rate estimating equations in simultaneous pancreas-kidney transplant recipients: a single center cohort study

Author: Luciano Selistre, Olivier Thaunat, Lionel Badet, Allyriane Dantec, Vandréa De Souza, Antoine Sicard, Fanny Buron, Emmanuel Morelon, Thomas Rimmelé, Sandrine Lemoine, Laurence Dubourg, Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Universidade de Caxias do Sul, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anesthésie-réanimation [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Urologie et Chirurgie de la Transplantation, Hôpital Edouard Herriot [CHU - HCL], Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique UMR 5305 (LBTI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, medicine.medical_specialty, Population, Urology, Renal function, 030209 endocrinology & metabolism, Estimating equations, creatinine-based GFR estimating equations, Single Center, Kidney Function Tests, Kidney transplant, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Medicine, Humans, 030212 general & internal medicine, Cystatin C, Renal Insufficiency, Chronic, education, simultaneous pancreas-kidney transplantation, Transplantation, Creatinine, education.field_of_study, glomerular filtration rate, business.industry, Reproducibility of Results, Middle Aged, Kidney Transplantation, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, chemistry, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Regression Analysis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Pancreas Transplantation, business, Cohort study
Abstract: International audience; Estimating glomerular filtration rate (GFR) is important for clinical management and research studies in simultaneous pancreas-kidney transplantation (SPK) recipients. No study has specifically investigated the reliability of recent creatinine-based GFR estimating equations in this singular population. We assessed the performances of CKD-EPI, MDRD, Schwartz-2009, Schwartz-Lyon, Lund-Malmo and Full Age Spectrum equations for estimating GFR after SPK. 126 patients were included. GFR was measured by a reference method (mGFR) one year after SPK and estimated with the different equations from a standardized measure of serum creatinine. Relative bias, precisions, 10% and 30% accuracies (P30) were used to determine equations reliability. Ages ranged from 29 to 58. Mean mGFR was 56.3 \textpm 13.3 [23.6-92.5] ml/min/1.73 m2 . In the whole population, P30 of the CKD-EPI and MDRD equations were 42% (38.0; 46.0) and 65% (61.5; 69) respectively. As compared to the other equations, the Schwartz-Lyon equation was significantly more accurate (P30 = 86.0% [83.5-88.0], P \textless 0.01) and less biased (1.13 [1.06-1.19], P \textless 0.01). Conclusions were similar whatever the age class (\textless40 or >=40) and mGFR level (\textless60 or >=60 ml/min/1.73 m2 ). This study suggests that the CKD-EPI and MDRD equations have poor performances in SPK recipients and that the Schwartz-Lyon equation is a reliable alternative.
Published: 2018

31. Clinical Assessment of a Nocardia PCR-Based Assay for Diagnosis of Nocardiosis

Author: Daniel Mathieu, Claire Rouzaud, David Lebeaux, Eric Farfour, Emilie Catherinot, Felipe Suarez, Emmanuelle Bergeron, Jean-Philippe Lengelé, Fabrice Larosa, Olivier Lortholary, Jean-Louis Christophe, Veronica Rodriguez-Nava, Anne Scemla, C. Delavaud, Sylvain Poirée, Frédéric Méchaï, Stéphane Durupt, Université Paris Descartes - Paris 5 (UPD5), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Service de pneumologie [Hôpital Foch], Hôpital Foch [Suresnes], Service des maladies infectieuses et tropicales, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Transplantation Rénale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier Universitaire de Lille (CHU de Lille), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Besancon, Dept Hematol, Besancon, France, Partenaires INRAE, Grand Hopital de Charleroi, Institut Pasteur [Paris], Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Bourse Junior 2015-Societe de Pathologie Infectieuse de Langue Francaise, We thank Frédéric Imbert (Montélimar) and Patrick Lamarche (Fontenay-le-Comte), Caroline Elie (Unité de Recherche Clinique/Centre d'Investigation Clinique Paris Descartes Necker Cochin, Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants Malades, Paris, France), Emilie Cardot (Service de Microbiologie, Hôpital Foch, Suresnes, France), Hervé Lecuyer (Laboratoire de Microbiologie, Hôpital Necker-Enfants Malades, APHP, Paris, France), and Violaine Walewski (Laboratoire de Microbiologie, Hôpital Avicenne, APHP, Bobigny, France) for their help during the study. We thank Karen Pickett for her editorial suggestions., Institut Pasteur [Paris] (IP), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Lung Diseases, Male, Opportunistic infection, SAMPLES, FEATURES, [SDV]Life Sciences [q-bio], Colony Count, Microbial, Positive control, Negative control, ANTIMICROBIAL SUSCEPTIBILITY PATTERNS, Gastroenterology, Polymerase Chain Reaction, Nocardia, law.invention, COLONIZATION, law, RNA, Ribosomal, 16S, Child, Polymerase chain reaction, Aged, 80 and over, biology, Nocardiosis, Middle Aged, 3. Good health, Hospitalization, PCR, Child, Preschool, Female, Nocardia Infections, Microbiology (medical), Adult, medicine.medical_specialty, Adolescent, 030106 microbiology, Opportunistic Infections, TRANSPLANT RECIPIENTS, Sensitivity and Specificity, 03 medical and health sciences, Immunocompromised Host, Young Adult, Internal medicine, medicine, Humans, nocardiosis, Aged, business.industry, Bacteriology, DNA, TAXONOMY, medicine.disease, biology.organism_classification, Multicenter study, immunocompromised hosts, business, SPP
Abstract: The diagnosis of nocardiosis, a severe opportunistic infection, is challenging. We assessed the specificity and sensitivity of a 16S rRNA Nocardia PCR-based assay performed on clinical samples. In this multicenter study (January 2014 to April 2015), patients who were admitted to three hospitals and had an underlying condition favoring nocardiosis, clinical and radiological signs consistent with nocardiosis, and a Nocardia PCR assay result for a clinical sample were included. Patients were classified as negative control (NC) (negative Nocardia culture results and proven alternative diagnosis or improvement at 6 months without anti- Nocardia treatment), positive control (PC) (positive Nocardia culture results), or probable nocardiosis (positive Nocardia PCR results, negative Nocardia culture results, and no alternative diagnosis). Sixty-eight patients were included; 47 were classified as NC, 8 as PC, and 13 as probable nocardiosis. PCR results were negative for 35/47 NC patients (74%). For the 12 NC patients with positive PCR results, the PCR assay had been performed with respiratory samples. These NC patients had chronic bronchopulmonary disease more frequently than did the NC patients with negative PCR results (8/12 patients [67%] versus 11/35 patients [31%]; P = 0.044). PCR results were positive for 7/8 PC patients (88%). There were 13 cases of probable nocardiosis, diagnosed solely using the PCR results; 9 of those patients (69%) had lung involvement (consolidation or nodule). Nocardia PCR testing had a specificity of 74% and a sensitivity of 88% for the diagnosis of nocardiosis. Nocardia PCR testing may be helpful for the diagnosis of nocardiosis in immunocompromised patients but interpretation of PCR results from respiratory samples is difficult, because the PCR assay may also detect colonization.
Published: 2018

32. Poor Patient and Graft Outcome After Induction Treatment by Antithymocyte Globulin in Recipients of a Kidney Graft After Nonrenal Organ Transplantation

Author: Thi Van Ha Nguyen, Jean-Paul Soulillou, Antoine Sicard, Pauline Houssel-Debry, Stéphanie Malard-Castagnet, Katy Trébern-Launay, Valérie Garrigue, Julie Laurent, Vered Padler-Karavani, Christophe Legendre, Magali Giral, Sophie Brouard, Michèle Treilhaud, Anne Cesbron, Hélène Perreault, Xi Chen, Michèle Kessler, Lionel Rostaing, Shani Leviatan Ben-Arye, Hoa Le Mai, Georges Karam, Emmanuel Morelon, Sophie Girerd, Evelyn Ang, Hai Yu, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Cell Research and Immunology, Tel Aviv University (TAU), Department of Chemistry [Univ California Davis] (Chemistry - UC Davis), University of California [Davis] (UC Davis), University of California (UC)-University of California (UC), Department of Chemistry [Winnipeg, MB, Canada], University of Manitoba [Winnipeg], Manitoba Centre for Proteomics and Systems Biology [Winnipeg, MB, Canada], Methodomics, Etablissement Français du Sang [Nantes], Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Chirurgie Hépatobiliaire et Digestive [Rennes] = Hepatobiliary and Digestive Surgery [Rennes], CHU Pontchaillou [Rennes], Service Néphrologie et transplantation rénale Adultes [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'urologie, Hôtel-Dieu, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Degauque, Nicolas, Tel Aviv University [Tel Aviv], Department of Chemistry Davis, University of California-University of California, Département de Néphrologie et Transplantation d'organes, Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service de Chirurgie Hépatobiliaire et Digestive [Rennes], Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Kidney Disease, [SDV.IMM] Life Sciences [q-bio]/Immunology, medicine.medical_treatment, Renal and urogenital, lcsh:Surgery, 030230 surgery, Organ transplantation, 03 medical and health sciences, Team2, 0302 clinical medicine, Team4, Internal medicine, medicine, CRTI, Kidney transplantation, Transplantation, Kidney, biology, business.industry, Proportional hazards model, Prevention, Immunosuppression, Organ Transplantation, lcsh:RD1-811, medicine.disease, Kidney Transplantation, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Propensity score matching, biology.protein, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, [SDV.IMM]Life Sciences [q-bio]/Immunology, Antibody, business
Abstract: Supplemental digital content is available in the text., Background End-stage renal failure occurs in a substantial number of patients having received a nonrenal transplantation (NRT), for whom a kidney transplantation is needed. The medical strategy regarding the use of immunosuppression (IS) for a kidney graft in patients after an NRT is not well established. The prekidney grafts long-term IS advocates for a mild induction, such as using anti-IL-2R antibodies, whereas addition of new incompatibilities and anti-HLA preimmunization may suggest using stronger IS such as induction by polyclonal antithymocyte globulins (ATG). Methods We performed Cox multivariate and propensity score analysis of our validated transplant database to study the impact of the type of induction therapy on kidney graft survival of recipients of a kidney graft after NRT. Results We report here that kidney transplantation after NRT treated with an ATG induction has a poorer outcome (kidney and recipient survival) than that with an anti–IL-2R induction. After accounting for potential baseline differences with a multivariate Cox model, or by adjusting on a propensity score, we found that despite patients having received ATG cumulate more risk factors, ATG appears independently involved. As animal-derived biotherapeutics induce antiglycan antibodies and particularly anti–N-glycolylneuraminic acid (Neu5Gc) IgGs which may activate endothelial cells in patients and grafts, we also investigated the magnitude and the nature of the anti-Neu5Gc elicited by the induction and showed that induction was associated with a shift in anti-Neu5Gc IgG repertoire. Possible reasons and mechanisms of a deleterious ATG usage in these patients are discussed. Conclusions Our study suggests that ATG induction after a kidney transplantation in recipients already under maintenance IS for a NRT should be used cautiously.
Published: 2018

33. Mechanisms underlying human genetic diversity: consequence for antigraft antibody responses

Author: Lorenzo Signorini, Rainer Oberbauer, Roman Reindl-Schwaighofer, Olivier Thaunat, Andreas Heinzel, Department of Internal Medicine III, Hanuschspital, Department of Diagnostics and Public Health [Verona] (UNIVR | DDSP), Università degli studi di Verona = University of Verona (UNIVR), Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), University of Verona (UNIVR), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Graft Rejection, Autoimmunity, Human leukocyte antigen, Human genetic variation, Computational biology, 030230 surgery, alloimmunity, Minor Histocompatibility Antigens, 03 medical and health sciences, 0302 clinical medicine, HLA Antigens, Isoantibodies, Transplantation Immunology, Genetic variation, Minor histocompatibility antigen, Medicine, antibodies, Humans, Genotyping, Genome, business.industry, Genome, Human, Alloimmunity, Genetic Variation, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Histocompatibility, omics, Transplantation, 030104 developmental biology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, rejection, business, Human, transplantation
Abstract: International audience; This review focuses on the emerging concept of genomewide genetic variation as basis of an alloimmune response. Chronic antibody-mediated rejection is the major cause of long-term graft loss and growing evidence supports the clinical relevance of HLA but also non-HLA related alloimmune responses. Several polymorphic gene products have been identified as minor histocompatibility antigens. The formation of donor-specific alloantibodies is driven by indirect allorecognition of donor-derived peptides representing a form of conventional T-cell response. With the availability of high-throughput sequencing and genotyping technologies, the identification of genomewide genetic variation and thus mismatches between organ donors and graft recipients has become feasible. First clinical data linking genetic polymorphism and clinical outcome have been published and larger studies are currently under way. Protein arrays have successfully been used to identify a large variety of non-HLA antibodies in kidney transplant recipients and the availability of customizable peptide arrays made screening for linear epitopes on an individual patient level feasible. This review provides a summary of the recent findings in histocompatibility matching in the field of solid organ transplantation and complements it with a clear workflow for assessing the impact of genetic differences in protein-coding genes in solid organ transplantation.
Published: 2018

34. COLT: Ten years of research in lung transplantation, results and perspectives

Author: Tissot, A., Foureau, A., Brosseau, C., Danger, R., Roux, A., Bernasconi, E., Gomez, C., Durand, M., Picard, B. R., Le Pavec, J., Claustre, J., Lacoste, P., Benmerad, M., Pain, M., Siroux, V., Royer, P. -J., Mordant, P., Reynaud-Gaubert, M., Kessler, R., Brugiere, O., Mornex, J. -F, Dromer, C., Dahan, M., Knoop, C., Boussaud, V., Koutsokera, A., Botturi-Cavailles, K., Durand, E., Loy, J., Nicod, L., Pison, C., Brouard, S., Blanc, F. -X., Magnan, A., Colt, Consortium, Immunoregulation And Immunointervention in Transplantation and Autoimmunity (Team 4 - U1064 Inserm - CRTI), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Laboratoire d'étude des marériaux, Université de Brest (UBO), Service de pneumologie [Hôpital Foch], Hôpital Foch [Suresnes], CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pneumologie et Réanimation, Centre de reference de l'hypertension artérielle pulmonaire, Hôpital Antoine Béclère, Assistance Publique - Hôpitaux de Paris (AP-HP), Université Paris Sud (Paris 11), Dr SPOC, Paris, Center for Public Health Research (CSISP), University of Valencia, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service de Pneumologie, Nouvel Hôpital Civil Strasbourg, CHU Bordeaux [Bordeaux], Ecole Nationale Supérieure de Chimie de Rennes (ENSCR), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Intervention, innovation, imagerie, ingénierie en santé - UFC (I4S), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), ANR-17-CE17-0008,Biket,Cellules B GZMB+, un facteur clé de l'immunité chez l'homme?(2017), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de transplantation pulmonaire [Hôpital Foch, Suresnes] (Pneumologie), Hôpital Foch [Suresnes]-Centre de fibrose kystique adulte [Hôpital Foch, Suresnes], Laboratoire d'étude des Interactions Sol - Agrosystème - Hydrosystème (UMR LISAH), Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut de Recherche pour le Développement (IRD [ Madagascar])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Ecole Nationale Supérieure de Chimie de Rennes, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Université Clermont Auvergne (UCA), Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF), and Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)
Subjects: Cohort Studies, Biomedical Research, Postoperative Complications, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Chronic Disease, Graft Survival, Humans, History, 20th Century, Primary Graft Dysfunction, History, 21st Century, ComputingMilieux_MISCELLANEOUS, Lung Transplantation
Abstract: National audience
Published: 2018

35. Hypothermic pulsatile preservation of kidneys from uncontrolled deceased donors after cardiac arrest - a retrospective study

Author: Vannary Meas Yedid, Thomas Rimmelé, Alexandre Faure, Palmina Petruzzo, Xavier Matillon, Lionel Badet, Emmanuel Morelon, Ricardo Codas, Olivier Thaunat, Maud Rabeyrin, Fabrice Danjou, William Hanf, Claire Delsuc, Service d'Urologie et Chirurgie de la Transplantation, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hôpital Saint Camille, Department of Medical Sciences, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service d'anesthésie-réanimation [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Département de Pathologie [CHU Lyon-Sud - HCL], Analyse d'images biologiques - Biological Image Analysis (BIA), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Alpes-Léman - CHAL, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: Graft Rejection, Male, Time Factors, medicine.medical_treatment, 030232 urology & nephrology, Pulsatile flow, 030230 surgery, outcomes, Cohort Studies, 0302 clinical medicine, Warm Ischemia, Kidney transplantation, uncontrolled deceased donors, Graft Survival, Statistics, Organ Preservation, perfusion machine, Treatment Outcome, Anesthesia, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Perfusion, medicine.medical_specialty, Tissue and Organ Procurement, Risk Assessment, Statistics, Nonparametric, 03 medical and health sciences, Extracorporeal Membrane Oxygenation, Resistance Index, Extracorporeal membrane oxygenation, medicine, Humans, Nonparametric, Cardiopulmonary resuscitation, Retrospective Studies, Transplantation, Inulin Clearance, business.industry, Retrospective cohort study, medicine.disease, Kidney Transplantation, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Surgery, Heart Arrest, Linear Models, business, donor management, Follow-Up Studies
Abstract: Kidneys from uncontrolled donors after cardiac arrest (uDCD) suffer from a period of warm ischemia between cardiac arrest and cold flushing. Aim of the study was to evaluate renal outcomes of uDCD kidneys selected on the basis of renal Resistance Index (RI) and its influence on graft function and survival. The study included 44 kidneys procured from 26 uDCD starting 1.1.2006 until 31.12.2013. The donors (Maastricht category II) underwent cardiopulmonary resuscitation by assisted ventilation and chest compression; the organs were preserved with “in situ” cold perfusion or a normothermic regional perfusion. All kidneys were perfused on hypothermic (1-4°C) pulsatile perfusion machine (RM3, Waters Medical System) and discarded when RI≥0.5 mmHg/mL/min after 6 hours of perfusion. There was one (2.2%) primary non-function, while 37 recipients (84.1%) experienced delayed graft function. Graft survival was 97.6% at 1 and 3 post-transplantation years. Linear regression models showed that lower values of RI at the end of perfusion were associated to higher values of MDRD at 3 (p=0.049) and 6 months after transplantation (p=0.010) and to higher values of inulin clearance at 1 year (p=0.030). RI showed to be a useful tool to select uDCD kidneys allowing to achieve good clinical results. This article is protected by copyright. All rights reserved.
Published: 2017

36. Value of biomarkers for predicting immunoglobulin A vasculitis nephritis outcome in an adult prospective cohort

Author: Claire Demongeot, Manuelle Viguier, Jean-Jacques Boffa, Stéphanie Tellier, Margarita Hurtado-Nedelec, Vincent Pestre, Gérard Cheron, Guillaume Burda, Martin Flamant, Héloïse Flament, Jérôme Verine, Alexandre Seidowsky, E Bourrat, Stéphane Decramer, Mathilde de Menthon, Karine Brochard, Karim Bouchireb, Maud Bezier, Evangeline Pillebout, Fabrice Mihout, Martine Bagot, Olivier Fain, Maya Halabi-Tawil, Agnès Jamin, Philippe Remy, Sonia Azib, Vincent Audard, Monique Dehoux, Jacqueline Rivet, Quentin Raimbourg, Denis Viglietti, Alexis Mathian, Laure Champion, Guillaume Bussone, Bertrand Godeau, Eric Daugas, Anne Saussine-Hickman, Antoine Froissart, Eric Thervet, Elisa Funck-Brentano, Alain Robert, Laureline Berthelot, Nathalie Vittoz, Nicolas Limal, Denis Glotz, Georges Deschênes, Isabelle Halphen, Theresa Kwon, Laurence Vrigneaud, Pierre Housset, Sophie Georgin-Lavialle, Florence Cordoliani, Arsene Mekinian, Virginia Sauvaget, Philippe Grimbert, Jean Christophe Mercier, Philippe Vanhille, Véronique Baudouin, François Vrtovsnik, Agathe Raynaud-Simon, Renato C. Monteiro, Jean-David Bouaziz, Leila Tricot, Laurène Dehoux, Melissa Pierre, Alexandre Karras, Laure Dehen, Céline Lebas, Nathalie Bocquet, Marc Fila, Claire Dossier, Thomas Quemeneur, Maryam Piram, Coralie Bloch-Queyrat, Antoine Dossier, David Verhelst, Anne Maisin, Olivier Benveniste, Dominique Farge, Charlotte Fite, Loïc Guillevin, Rémi Salomon, Emmanuelle Vidal-Petiot, Zahir Amoura, Valérie Caudwell, Assia Smail, Philippe Bouvier, Michel Delahousse, Gentiane Monsel, Jonathan M. Chemouny, Hamza Ayari, Anne-Sophie Verhoeven, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Néphrologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie [Bichat - Claude Bernard], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), UMR 1599, Centre National de la Recherche Scientifique (CNRS), Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de néphrologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, Service de néphrologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Institut Mondor de recherche biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de neuropédiatrie et maladies métaboliques [CHU Robert-Debré], Sorbonne Université (SU), Hôpital Saint-Louis, Institut National de l'Environnement Industriel et des Risques (INERIS), Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Dermatologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Department of dermatology, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service Pédiatrique [Toulouse], CHU Toulouse [Toulouse], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Sud Francilien, Department of Dermatology, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de dermatologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service de transplantation rénale, Hôpital Foch [Suresnes], AP-HP, Service de Néphrologie Pédiatrique, Hôpital Robert Debré, Paris, Hôpital Bicêtre, Service de Médecine Interne, Centre de Recherche Saint-Antoine (UMRS893), Physiopathologie et Epidemiologie de l'Insuffisance Respiratoire, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine interne, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de dermatologie, Service de Physiologie [Bichat-Claude Bernard], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Physiopathologie des maladies génétiques d'expression pédiatrique, Service de médecine interne [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), AP-HP Hôpital universitaire Robert-Debré [Paris], Service de Néphrologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Département de Néphrologie = Service de Néphrologie et Dialyses [CHU Tenon], CHU Tenon [AP-HP], Service de Pédiatrie Générale et Rhumatologie Pédiatrique, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, CH Valenciennes, Université Paris Descartes - Paris 5 (UPD5), Gvh et Gvl : Physiopathologie Chez l'Homme et Chez l'Animal, Incidence et Role Therapeutique, Développement et Communication Chimique chez les Insectes (DCCI), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Service de néphrologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre de Référence du Sud Ouest des Maladies Rénales Rares, Service de néphrologie adultes [CHU Necker], Service de médecine interne et néphrologie, Centre Hospitalier Henri Duffaut (Avignon), Service de Néphrologie [Valenciennes], Centre Hospitalier de Valenciennes, Service d'anatomo-pathologie [Paris], Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor [Créteil], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), CHU Toulouse [Toulouse]-Hôpital des Enfants, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CH Evry-Corbeil, Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), and Hôpital Cochin [AP-HP]
Subjects: 0301 basic medicine, Immunoglobulin A, Adult, Male, medicine.medical_specialty, IgA Vasculitis, Urinary system, 030232 urology & nephrology, Antigen-Antibody Complex, Gastroenterology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, medicine, Humans, Prospective Studies, 10. No inequality, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Aged, Transplantation, Proteinuria, Nephritis, biology, business.industry, Middle Aged, medicine.disease, Prognosis, 3. Good health, 030104 developmental biology, IgA vasculitis, ROC Curve, Nephrology, biology.protein, Female, medicine.symptom, Vasculitis, business, Biomarkers, Systemic vasculitis, Glomerular Filtration Rate
Abstract: Background Henoch-Schonlein purpura, more recently renamed immunoglobulin A vasculitis (IgAV), is a systemic vasculitis characterized by IgA deposits. The current markers used to assess IgAV inaccurately evaluate the risk of nephritis occurrence and its long-term outcomes. The current study assessed biomarkers of nephritis outcomes. Methods This French multicentre prospective study enrolled 85 adult patients at the time of disease onset. Patients were assessed for clinical and biological parameters and re-examined after 1 year. Immunoglobulins, cytokines, IgA glycosylation, IgA complexes and neutrophil gelatinase-associated lipocalin (NGAL) concentrations were assessed in blood and urine. Results We identified 60 patients with IgAV-related nephritis (IgAV-N) and 25 patients without nephritis (IgAV-woN). At the time of inclusion (Day 1), the serum levels of galactose-deficient IgA1 (Gd-IgA1) and urinary concentrations of IgA, IgG, IgM, NGAL, interleukin (IL)-1β, IL-6, IL-8, IL-10, IgA-IgG and IgA-sCD89 complexes were higher in the IgAV-N patients than in the IgAV-woN patients (P
Published: 2017

37. Grams ME, Sang Y, Ballew SH, et al, for the Chronic Kidney Disease Prognosis Consortium. Predicting timing of clinical outcomes in patients with chronic kidney disease and severely decreased glomerular filtration rate. Kidney Int. 2018;93:1442–1451

Author: Remy, Philippe, Audard, Vincent, Natella, Pierre André, Pelle, Gaëlle, Dussol, Bertrand, Leray-Moragues, Hélène, Bouachi, Khedidja, Dantal, Jacques, Vrigneaud, Laurence, Karras, Alexandre, Pourcine, Frank, Gatault, Philippe, Grimbert, Philippe, Ait Sahlia, Nawelle, Moktefi, Anissa, Daugas, Eric, Rigothier, Claire, Bastuji-Garin, Sylvie, Sahali, Dil, Aldigier, Jean Claude, Bataille, Pierre, Canaud, Bernard, Chauveau, Dominique, Combe, Christian, Choukroun, Gabriel, Cornec-Legall, Emilie, Dahan, Karine, Delahousse, Michel, Desvaux, Dominique, Deteix, Patrice, Durrbach, Antoine, Esnault, Vincent, Essig, Marie, Fievet, Patrick, Frouget, Thierry, Guerrot, Dominique, Godin, Michel, Gontiers-Picard, Annie, Gosselin, Morgane, Hanrotel-Saliou, Catherine, Heng, Anne-Elisabeth, Huart, Antoine, Humbert, Antoine, Kofman, Tomek, Hummel, Aurélie, Lang, Philippe, Laville, Maurice, Lemeur, Yannick, Malvezzi, Paolo, Matignon, Marie, Mesbah, Rafik, Moulin, Bruno, Muller, Sandrine, Olagne, Jerome, Pardon, Agathe, Provôt, François, Queffeulou, Guillaume, Plaisier, Emmanuelle, Raimbourg, Quentin, Rieu, Philippe, Stehlé, Thomas, Vanhille, Philippe, Astor, Brad, Levin, Adeera, Tang, Mila, Djurdjev, Ognjenka, Navaneethan, Sankar, Jolly, Stacey, Schold, Jesse, Nally, Joseph, Emberson, Jonathan, Townend, John, Landray, Martin, Feldman, Harold, Hsu, Chi-Yuan, Lash, James, Appel, Lawrence, Kalra, Philip, Ritchie, James, Maharajan, Raman, Middleton, Rachel, O’donoghue, Donal, Schneider, Markus, Kronenberg, Florian, Bärthlein, Barbara, Green, Jamie, Kirchner, H. Lester, Ho, Kevin, Marks, Angharad, Black, Corri, Prescott, Gordon, Fluck, Nick, Nakayama, Masaaki, Miyazaki, Mariko, Yamamoto, Tae, Yamada, Gen, Wang, Angela Yee-Moon, Cheung, Sharon, Wong, Sharon, Chu, Jessie, Wu, Henry, Garg, Amit, Mcarthur, Eric, Nash, Danielle, Shalev, Varda, Chodick, Gabriel, Blankestijn, Peter, Wetzels, Jack F.M., van Zuilen, Arjan, van den Brand, Jan, Inker, Lesley, Sarnak, Mark, Tighiouart, Hocine, Zhang, Haitao, Stengel, Bénédicte, Metzger, Marie, Flamant, Martin, Houillier, Pascal, Haymann, Jean-Philippe, Rios, Pablo, Mazzuchi, Nelson, Gadola, Liliana, Lamadrid, Verónica, Solá, Laura, Collins, John, Elley, C. Raina, Kenealy, Timothy, Moranne, Olivier, Couchoud, Cécile, Vigneau, Cécile, Brunskill, Nigel, Major, Rupert, Shepherd, David, Medcalf, James, Kovesdy, Csaba, Kalantar-Zadeh, Kamyar, Sumida, Keiichi, Potukuchi, Praveen, Heerspink, Hiddo J.L., de Zeeuw, Dick, Brenner, Barry, Carrero, Juan Jesus, Gasparini, Alessandro, Qureshi, Abdul Rashid, Elinder, Carl-Gustaf, Visseren, Frank L.J., van Der Graaf, Yolanda, Evans, Marie, Stendahl, Maria, Schön, Staffan, Segelmark, Mårten, Prütz, Karl-Göran, Naimark, David, Tangri, Navdeep, Mark, Patrick, Traynor, Jamie, Geddes, Colin, Thomson, Peter, Chang, Alex, Gansevoort, Ron, Köttgen, Anna, Levey, Andrew, Zhang, Luxia, Ballew, Shoshana, Chen, Jingsha, Coresh, Josef, Grams, Morgan, Kwak, Lucia, Matsushita, Kunihiro, Sang, Yingying, Surapaneni, Aditya, Woodward, Mark, Eckardt, Kai-Uwe, Hemmelgarn, Brenda, Wheeler, David, Winkelmayer, Wolfgang, Davis, John, Green, Danielle, Cheung, Michael, Green, Tanya, Mcmahan, Melissa, Molnar, Miklos, Service de néphrologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, Assistance Publique-Hôpitaux de Paris, Department of Pathology, Centre hospitalier universitaire Henri Mondor, F-94000 Créteil, France, Department of Nephrology and Transplantation, Foch Hospital, Chirurgie urologique et transplantation rénale [Hôpital de la Conception - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de néphrologie et transplantation, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Transplantation Urologie et Néphrologie, Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Néphrologie [Valenciennes], Centre Hospitalier de Valenciennes, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Néphrologie CHU TOURS, INSERM U955, équipe 21, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), UMR 1599, Centre National de la Recherche Scientifique (CNRS), Department of Nephrology, Transplantation and Dialysis, Bordeaux, Laboratoire d'Investigation Clinique (LIC), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Université de Lausanne = University of Lausanne (UNIL), Service de Néphrologie et Immunopathologie Clinique, Centre Hospitalier Universitaire de Toulouse, PRES Université de Toulouse, CHU Bordeaux [Bordeaux], Unité Médicale de Soins Intensifs, CHU Amiens-Picardie, CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Département de Néphrologie = Service de Néphrologie et Dialyses [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de transplantation rénale, Hôpital Foch [Suresnes], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service Néphrologie, Pôle REUNNIRH, CHU Clermont-Ferrand, U542, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie, Centre Hospitalier Universitaire de Nice (CHU Nice), Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Univers, Transport, Interfaces, Nanostructures, Atmosphère et environnement, Molécules (UMR 6213) (UTINAM), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Pontchaillou [Rennes], Service de Néphrologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Nouvelles Cibles Pharmacologiques de la Protection Endothéliale et de l'Insuffisance Cardiaque (EnVI), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de néphrologie, dialyse, aphérèses et transplantation, CHU Grenoble-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), CH Boulogne sur Mer, Service de Néphrologie et Transplantation, CHU Strasbourg, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Néphrologie [CHPC - Site Louis Pasteur], Site Louis Pasteur [CHPC], CH Centre Hospitalier Public du Cotentin (CHPC)-CH Centre Hospitalier Public du Cotentin (CHPC), Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie [Bichat - Claude Bernard], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Universitaire de Reims (CHU Reims), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Service de médecine interne et néphrologie, CH Valenciennes, Division of Nephrology [Vancouver, BC, Canada], University of British Columbia (UBC), Aberdeen University, Fraunhofer Institute for Secure Information Technology [Darmstadt] (Fraunhofer SIT), Fraunhofer (Fraunhofer-Gesellschaft), Division of genetic epidemiology, HMNC Brain Health-Molecular and Clinical Pharmacology-Innsbruck Medical University [Austria] (IMU), Department of electronic engineering, Chang Gung University, Institute of Applied Health Sciences, University of Aberdeen, Department of Medicine, The University of Hong Kong (HKU), Department of Nephrology [Utrecht, Pays-Bas], University Medical Center [Utrecht], Department of Nephrology [Nijmegen, The Netherlands], Radboud University Medical Center [Nijmegen], Department of nephrology [Nimègue, Pays-Bas], Radboud Institute for Health Sciences [Nimègue, Pays-Bas], Radboud University Medical Center [Nijmegen]-Radboud University Medical Center [Nijmegen], Tufts Medical Center, Nanjing University of Aeronautics and Astronautics [Nanjing] (NUAA), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Physiologie [Bichat-Claude Bernard], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service de Physiologie [Georges-Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Center for Research in Agricultural Genomics, Directora Division Epidemiologia [Montevideo, Uruguay], Ministerio de Salud Publica, Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), Agence de la biomédecine [Saint-Denis la Plaine], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Division of Nephrology, Department of Medicine, Vanderbilt University School of Medicine [Nashville], Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet [Stockholm], Julius Center for Health Sciences and Primary Care, Division of Drug Research/Clinical Pharmacology, Department of Medicine and Health, Faculty of Health Sciences, Linköping University (LIU), Department of Nephrology [Groningue, Pays-Bas], University Medical Center Groningen [Groningen] (UMCG), Renal Division [Beijing, China], Peking University [Beijing], The Georges Institute for International Health, The University of Sydney, Department of Nephrology and Hypertension [Erlangen, Germany], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Baylor College of Medicine (BCM), Baylor University, Université de Lausanne (UNIL), Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Service de néphrologie [CHPC, Cherbourg-en-Cotentin], CHPC - Site Louis Pasteur, Centre Hospitalier Public du Cotentin (CHPC)-Centre Hospitalier Public du Cotentin (CHPC), Innsbruck Medical University [Austria] (IMU)-HMNC Brain Health-Molecular and Clinical Pharmacology, Radboud University Medical Centre [Nijmegen, The Netherlands], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Peking University First Hospital [China]-Peking University Institute of Nephrology [China], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor [Créteil], Service Médecine interne et immunopathologie clinique [CHU Toulouse], Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), HMNC Brain Health-Molecular and Clinical Pharmacology-Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Henri Mondor, Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut Mondor de Recherche Biomédicale (IMRB), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Centre Hospitalier Universitaire de Clermont-Ferrand, Université de Rouen Normandie (UNIROUEN), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Service de Néphrologie, Dialyse, Aphérèses et Transplantation [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Saint-Antoine [APHP], Centre Hospitalier du Cotentin, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Fraunhofer Institute for Secure Information Technology [Darmstadt] (SIT), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Méthodes Algorithmes pour l'Ordonnancement et les Réseaux (MAORE), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Nephrology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], media_common.quotation_subject, 030232 urology & nephrology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, In patient, 030212 general & internal medicine, mycophenolate, media_common, clinical trial, Art, medicine.disease, Optimal management, Treatment efficacy, 3. Good health, Transplantation, Cohort, idiopathic nephrotic syndrome, Humanities, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, steroids, Kidney disease, Cohort study
Abstract: The Chronic Kidney Disease (CKD) Prognosis Consortium is a collaborative author of the above-mentioned article. The CKD Prognosis Consortium investigators/collaborators are as follows: • African American Study of Kidney Disease and Hypertension (AASK): Brad Astor, Lawrence J. Appel; Canadian Study of Prediction of Death, Dialysis and Interim Cardiovascular Events (CanPREDDICT): Adeera Levin, Mila Tang, Ognjenka Djurdjev; Cleveland Clinic CKD Registry Study (CCF): Sankar D. Navaneethan, Stacey E. Jolly, Jesse D. Schold, Joseph V. Nally Jr.; Chronic Renal Impairment in Birmingham (CRIB): David C. Wheeler, Jonathan Emberson, John Townend, Martin Landray; Chronic Renal Insufficiency Cohort Study (CRIC): Harold I. Feldman, Chi-yuan Hsu, James P. Lash, Lawrence J. Appel; Chronic Renal Insufficiency Standards Implementation Study (CRISIS): Philip A. Kalra, James P. Ritchie, Raman Maharajan, Rachel J. Middleton, Donal J. O'Donoghue; German Chronic Kidney Disease Study (GCKD): Kai-Uwe Eckardt, Markus P. Schneider, Anna Kottgen, Florian Kronenberg, Barbara Barthlein; Geisinger Health System: Alex R. Chang, Jamie A. Green, H. Lester Kirchner, Kevin Ho; Grampian Laboratory Outcomes, Morbidity and Mortality Studies – 2 (GLOMMS2): Angharad Marks, Corri Black, Gordon J. Prescott, Nick Fluck; Gonryo Study: Masaaki Nakayama, Mariko Miyazaki, Tae Yamamoto, Gen Yamada; Hong Kong CKD Studies: Angela Yee-Moon Wang, Sharon Cheung, Sharon Wong, Jessie Chu, Henry Wu; Ontario Institute for Clinical Evaluative Sciences, Provincial Kidney, Dialysis and Transplantation program (ICES KDT): Amit X. Garg, Eric McArthur, Danielle M. Nash; Maccabi Health System: Varda Shalev, Gabriel Chodick; Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of a Nurse Practitioner (MASTERPLAN): Peter J. Blankestijn, Jack F.M. Wetzels, Arjan D. van Zuilen, Jan A. van den Brand; Modification of Diet in Renal Disease Study (MDRD): Andrew S. Levey, Lesley A. Inker, Mark J. Sarnak, Hocine Tighiouart; Nanjing CKD Network Cohort Study (Nanjing CKD): Haitao Zhang; NephroTest Study (NephroTest): Benedicte Stengel, Marie Metzger, Martin Flamant, Pascal Houillier, Jean-Philippe Haymann; National Renal Healthcare Program – Uruguay (NRHP-URU): Pablo G. Rios, Nelson Mazzuchi, Liliana Gadola, Veronica Lamadrid, Laura Sola; New Zealand Diabetes Cohort Study (NZDCS): John F. Collins, C. Raina Elley, Timothy Kenealy; Parcours de Soins des Personnes Agees (PSPA): Olivier Moranne, Cecile Couchoud, Cecile Vigneau; Primary-Secondary Care Partnership to Prevent Adverse Outcomes in Chronic Kidney Disease (PSP CKD): Nigel J. Brunskill, Rupert W. Major, David Shepherd, James F. Medcalf; Racial and Cardiovascular Risk Anomalies in CKD Cohort (RCAV): Csaba P. Kovesdy, Kamyar Kalantar-Zadeh, Miklos Z. Molnar, Keiichi Sumida, Praveen K. Potukuchi; Reduction of Endpoints in Non-insulin Dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan (RENAAL): Hiddo J.L. Heerspink, Dick de Zeeuw, Barry Brenner; Stockholm CREAtinine Measurements Cohort (SCREAM): Juan Jesus Carrero, Alessandro Gasparini, Abdul Rashid Qureshi, Carl-Gustaf Elinder; Second Manifestations of ARTerial Disease Study (SMART): Frank L.J. Visseren, Yolanda van der Graaf; Swedish Renal Registry CKD Cohort (SRR CKD): Marie Evans, Maria Stendahl, Staffan Schon, Marten Segelmark, Karl-Goran Prutz; Sunnybrook Cohort: David M. Naimark, Navdeep Tangri; West of Scotland CKD Study: Patrick B. Mark, Jamie P. Traynor, Colin C. Geddes, Peter C. Thomson.• CKD Prognosis Consortium Steering Committee: Alex R. Chang, Josef Coresh (Chair), Ron T. Gansevoort, Morgan E. Grams, Anna Kottgen, Andrew S. Levey, Kunihiro Matsushita, Mark Woodward, Luxia Zhang.• CKD Prognosis Consortium Data Coordinating Center: Shoshana H. Ballew (Assistant Project Director), Jingsha Chen (Programmer), Josef Coresh (Principal Investigator), Morgan E. Grams (Director of Nephrology Initiatives), Lucia Kwak (Programmer), Kunihiro Matsushita (Director), Yingying Sang (Lead Programmer), Aditya Surapaneni (Programmer), Mark Woodward (Senior Statistician).• Kidney Disease Improving Global Outcomes (KDIGO) Controversies Conference on Prognosis and Optimal Management of Patients with Advanced CKD: Kai-Uwe Eckardt (Conference Co-Chair), Brenda R. Hemmelgarn (Conference Co-Chair), David C. Wheeler (KDIGO Co-Chair), Wolfgang C. Winkelmayer (KDIGO Co-Chair), John Davis (CEO), Danielle Green (Managing Director), Michael Cheung (Chief Scientific Officer), Tanya Green (Communications Director), Melissa McMahan (Programs Director).
Published: 2018

38. Community-acquired Legionnaires' disease in a renal transplant recipient with unclear incubation period: the importance of molecular typing

Author: Thomas Bénet, Fanny Buron, S. Jarraud, M.C. Nicolle, Ghislaine Descours, Emmanuel Morelon, Laetitia Beraud, M. Brunet, Philippe Vanhems, P. Cassier, Unité d'Hygiène et d'Épidémiologie, Groupement hospitalier Nord, Lyon, parent, Centre National de Référence des Légionelles (CNR), Pathogenèse des légionelles- Legionella pathogenesis (LegioPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des pathogènes émergents -- Emerging Pathogens Laboratory (LPE-Fondation Mérieux), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, medicine.medical_specialty, Cellular immunity, Legionella, Disease, Incubation period, Immunocompromised Host, Postoperative Complications, Internal medicine, renal transplant, medicine, Humans, incubation period, Transplantation, biology, business.industry, oropharyngeal colonization, Middle Aged, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Kidney Transplantation, 3. Good health, Community-Acquired Infections, Molecular Typing, Pneumonia, Infectious Diseases, Renal transplant, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Legionnaires' disease, Legionnaires' Disease, Water Microbiology, business
Abstract: International audience; Transplant recipients are at risk of developing Legionnaires' disease (LD) because of impaired cellular immunity. Here, we describe a renal transplant recipient who developed LD at least 10 days after hospital admission and transplantation. The hospital water network was initially suspected, but further testing determined that the probable source was the patient's domestic water supply. Our report also suggests that the patient's immunosuppressed state may have switched potential colonization to pneumonia.
Published: 2015

39. Pregnancy outcomes in simultaneous pancreas and kidney transplant recipients: a national French survey study

Author: Marielle Catton, Georges Karam, Flora Brunner, Olivier Thaunat, Diego Cantarovich, Gabrielle Normand, Laure Esposito, Sophie Caillard, Georges Mourad, Emmanuel Morelon, Fanny Buron, Jean E. Serre, Lionel Badet, Jérôme Massardier, Philippe Grimbert, Service de Néphrologie Hospices Civils - hta - dialyse, Service d'Urologie et Chirurgie de la Transplantation, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service de néphrologie et hémodialyse [CHU de Strasbourg], CHU Strasbourg, Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Service de Néphrologie Transplantation, Institut de Transplantation Urologie-Néphrologie (ITUN), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Gestational hypertension, Adult, medicine.medical_specialty, Birth weight, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, kidney transplantation, 030230 surgery, simultaneous pancreas and kidney transplantation, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, medicine, Humans, Kidney transplantation, Retrospective Studies, Transplantation, Type 1 diabetes, Pregnancy, Fetus, Obstetrics, business.industry, Graft Survival, Pregnancy Outcome, Gestational age, medicine.disease, 3. Good health, Surgery, Pregnancy Complications, Diabetes Mellitus, Type 1, Treatment Outcome, Kidney Failure, Chronic, Female, France, Pancreas Transplantation, pregnancy, business, Follow-Up Studies
Abstract: International audience; Simultaneous pancreas and kidney transplantation (SPK) is currently the best therapeutic option for patients with type 1 diabetes and terminal renal failure. Renal transplantation restores fertility enabling women to pursue pregnancies. However, scarcity of available data on pregnancy outcomes in SPK impedes fair medical counseling. Medical files of all pregnancies that lasted >=3 months among recipients of functional SPK performed between 1990 and 2015 in France were retrospectively analyzed. Twenty-six pregnancies in 22 SPK recipients were identified. Main maternal complications included gestational hypertension (53.8%) and infections (50%). Cesarean section was performed in 73% of cases. Overall fetal survival was 92.6% with a mean gestational age of 34.2 \textpm 3 weeks. Four children (16.7% of live births) had a birth weight \textless10th percentile. Endocrine pancreas graft function remained stable during pregnancy. An acute kidney rejection occurred in two patients, one of which resulting in graft loss. Kidney and pancreas graft survival was, respectively, 96% and 100% at 1 year postconception and did not differ from controls. Pregnancy in SPK is feasible, but patients should be informed of the risks for the fetus, the mother, and the grafts. Planning of pregnancy in SPK women is key to allow a personalized multidisciplinary monitoring, which represents the most straightforward approach to optimize outcomes.
Published: 2017

40. mTOR inhibitors and risk of chronic antibody-mediated rejection after kidney transplantation: where are we now?

Author: Olivier Thaunat, Philippe Grimbert, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Oncology, Graft Rejection, medicine.medical_specialty, medicine.medical_treatment, Calcineurin Inhibitors, 030232 urology & nephrology, 030230 surgery, Pharmacology, donor-specific anti-HLA antibodies, 03 medical and health sciences, Mice, 0302 clinical medicine, Risk Factors, HLA Antigens, Isoantibodies, Models, Internal medicine, Concomitant Therapy, Medicine, Animals, Humans, PI3K/AKT/mTOR pathway, Kidney transplantation, mammalian target of rapamycin, Immunosuppression Therapy, Everolimus, business.industry, Animal, TOR Serine-Threonine Kinases, Immunosuppression, medicine.disease, everolimus, Kidney Transplantation, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Tissue Donors, 3. Good health, Calcineurin, Transplantation, sirolimus, Sirolimus, Models, Animal, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, antibody-mediated rejection, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, medicine.drug, transplantation
Abstract: Antibody-mediated rejection (AMR) usually starts with generation of donor-specific anti-HLA antibodies (DSA), arising from a B-cell response to antigen recognition. In vitro and preclinical data demonstrate that mammalian target of rapamycin (mTOR) inhibition attenuates the mTOR-mediated intracellular signaling pathway involved in AMR-related kidney damage. The limited available data from immunological studies in kidney transplant patients, however, have not shown such effects in vivo. In terms of clinical immunosuppression, the overriding influence on rates of de novo DSA (dnDSA) or AMR – regardless of the type of regimen – is patient adherence. To date, limited data from patients given mTOR inhibitor therapy with adequate concurrent immunosuppression, such as reduced-exposure calcineurin inhibitor (CNI) therapy, has not shown an adverse effect on the risk for dnDSA or AMR. Early switch to an mTOR inhibitor (
Published: 2017

41. Cum hoc sed non propter hoc

Author: E. Pouliquen, Olivier Thaunat, Laurence Kessler, Valérie Dubois, Chien-Chia Chen, Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service d'Endocrinologie - Diabète et Maladies Métaboliques, Hôpitaux Universitaires de Strasbourg, Etablissement français du sang- Rhône-Alpes [Lyon], Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, translational research/science, graft survival, MEDLINE, 030230 surgery, 03 medical and health sciences, Islets of Langerhans, 0302 clinical medicine, Risk Factors, Internal medicine, alloantibody, Immunology and Allergy, Medicine, Pharmacology (medical), ComputingMilieux_MISCELLANEOUS, Antilymphocyte Serum, Transplantation, business.industry, islet transplantation, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, animal models, Tissue Donors, rejection: antibody-mediated (ABMR), [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Antibody Formation, [SDV.IMM]Life Sciences [q-bio]/Immunology, Graft survival, business, Antibody formation, 030215 immunology
Abstract: International audience
Published: 2017

42. Computer-assisted topological analysis of renal allograft inflammation adds to risk evaluation at diagnosis of humoral rejection

Author: Vannary Meas-Yedid, Antoine Sicard, Maud Rabeyrin, Lionel Badet, Frédérique Dijoud, Valérie Dubois, Valérie Hervieu, Emmanuel Morelon, Alice Koenig, Stéphanie Ducreux, Jean-Christophe Olivo-Marin, Olivier Thaunat, Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Analyse d'images biologiques - Biological Image Analysis (BIA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Département d'anatomopathologie [Hôpital Femme Mère Enfant - HCL], Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Etablissement français du sang- Rhône-Alpes [Lyon], Département d'anatomopathologie, biopathologie, Centre Léon Bérard [Lyon], Service d'Urologie et Chirurgie de la Transplantation, Hôpital Edouard Herriot [CHU - HCL], Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Graft Rejection, Male, Pathology, Time Factors, Biopsy, 030232 urology & nephrology, Kaplan-Meier Estimate, 030230 surgery, Kidney, donor-specific antibodies, 0302 clinical medicine, Computer-Assisted, Glomerulonephritis, Isoantibodies, Diagnosis, Macrophage, Diagnosis, Computer-Assisted, Kidney transplantation, medicine.diagnostic_test, biology, Graft Survival, Humoral, Middle Aged, Allografts, Prognosis, Immunohistochemistry, 3. Good health, macrophages, medicine.anatomical_structure, Treatment Outcome, Nephrology, Complement C3d, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, antibody-mediated rejection, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, medicine.symptom, Antibody, Algorithms, Adult, medicine.medical_specialty, complement-binding DSA, Inflammation, allograft pathology, 03 medical and health sciences, Young Adult, Immune system, Predictive Value of Tests, Image Interpretation, Computer-Assisted, medicine, Humans, Image Interpretation, business.industry, Immunity, inflammation quantification, medicine.disease, Kidney Transplantation, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Immunity, Humoral, Immunology, biology.protein, business, Biomarkers
Abstract: International audience; Antibody-mediated rejection is associated with heterogeneous kidney allograft outcomes. Accurate evaluation of risk for graft loss at time of diagnosis is necessary to offer personalized treatment. In contrast with serological and molecular assessment, morpho-histological evaluation of antibody-mediated rejection lesions has not significantly evolved. This relies on Banff classifications designed to be of diagnostic discriminatory power rather than prognostic and face quantitative and qualitative limitations. Here we developed a method of Computer-assisted Analysis of Graft Inflammation (CAGI) to improve the classification of allograft inflammation. Digitization of immunostained biopsy sections, image processing and algorithm-driven analysis allowed quantification of macrophages, T cells, B cells, and granulocytes per unit surface of interstitium, capillaries or glomeruli. CAGI was performed on biopsy specimens of 52 patients with extensively phenotyped antibody-mediated rejection. Macrophage numbers in capillaries and interstitium, but not Banff scores or the amount of other immune cell subsets, correlated with donor-specific antibody (DSA) mean fluorescence intensity and DSA-C3d status. The quantity of macrophages in the interstitium and DSA-C3d status were the only independent predictors for significant allograft loss at the time of antibody-mediated rejection diagnosis (hazard ratio 3.71 and 2.34, respectively). A significant strategy integrating the DSA-C3d assay and the quantification of interstitial macrophages allowed identification of three groups with distinct renal prognosis: DSA-C3d-, DSA-C3d+/macrophages-low and DSAC3d+/macrophages-high. Thus, CAGI brings a missing piece to the antibody-mediated rejection puzzle by identifying morpho-histological processes that bridge in~vitro parameters of DSA pathogenicity and graft loss. Hence, this approach could be useful in future integrated strategies of risk evaluation.
Published: 2017

43. PARTIAL GRAFT LOSS OF A FACIAL TRANSPLANT AFTER DONOR SPECIFIC ANTIBODIES DEVELOPMENT

Author: Morelon, Emmanuel, Petruzzo, Palmina, Kanitakis, Jean, Dakpé, Stéphanie, Thaunat, Olivier, Dubois, Valerie, Choukroun, Gabriel, Testelin, Sylvie, Dubernard, Jean-Michel, Badet, Lionel, Devauchelle, Bernard, Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service d'Urologie et Chirurgie de la Transplantation, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Department of Medical Sciences, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Clinique Dermatologique, Département de chirurgie maxillofaciale et stomatologie [CHU d'Amiens-Picardie], CHU Amiens-Picardie, HLA Department, EFS Rhone-Alpes, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), and Département de transplantation et d'immunologie clinique [Hôpital Edouard Herriot, HCL]
Subjects: [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2017

44. Mature IgM-expressing plasma cells sense antigen and develop competence for cytokine production upon antigenic challenge

Author: Simon de Bernard, Morgan Taillardet, Thierry Defrance, Pascal Blanc, Ludovic Moro-Sibilot, Stephen L. Nutt, Laurent Genestier, Laurent Buffat, Antoine Sicard, Ferdinand Jagot, Renaud Colisson, Lucas Barthly, Olivier Thaunat, Thierry Fest, Sébastien Dussurgey, Sébastien This, Elias Hobeika, Paul Mondière, Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Mucosal Immunity, Vaccination, and Biometrics -- Immunité des muqueuses, vaccinations et biothérapies, AltraBio [Lyon], SFR Biosciences, École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Affymetrix, Institute of Immunology [Ulm], Universitätsklinikum Ulm - University Hospital of Ulm, Microenvironnement et cancer (MiCa), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Transplantation Rénale et d'Immunologie Clinique, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Université de Lyon, Division of Immunology, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, Victoria 3052, Australia., Region Rhones-Alpes ARC1, National Health and Medical Research Council of Australia [361646, 1054925], Victorian State Government Operational Infrastructure Support, [SFB 1074], Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: 0301 basic medicine, waldenstrom macroglobulinemia, Science, medicine.medical_treatment, Plasma Cells, blimp-1, B-cell receptor, Receptors, Antigen, B-Cell, General Physics and Astronomy, Bone Marrow Cells, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, General Biochemistry, Genetics and Molecular Biology, memory b-cells, 03 medical and health sciences, Antigen, medicine, Animals, Antigens, Antibody-Producing Cells, gene, bone-marrow, Multidisciplinary, CD40, biology, Gene Expression Profiling, breakpoint cluster region, Dextrans, differentiation, General Chemistry, immunity, Molecular biology, Isotype, 3. Good health, Mice, Inbred C57BL, Gene Ontology, 030104 developmental biology, Cytokine, Immunoglobulin M, compartments, responses, biology.protein, Cytokines, Antibody, immunoglobulin
Abstract: Dogma holds that plasma cells, as opposed to B cells, cannot bind antigen because they have switched from expression of membrane-bound immunoglobulins (Ig) that constitute the B-cell receptor (BCR) to production of the secreted form of immunoglobulins. Here we compare the phenotypical and functional attributes of plasma cells generated by the T-cell-dependent and T-cell-independent forms of the hapten NP. We show that the nature of the secreted Ig isotype, rather than the chemical structure of the immunizing antigen, defines two functionally distinct populations of plasma cells. Fully mature IgM-expressing plasma cells resident in the bone marrow retain expression of a functional BCR, whereas their IgG+ counterparts do not. Antigen boost modifies the gene expression profile of IgM+ plasma cells and initiates a cytokine production program, characterized by upregulation of CCL5 and IL-10. Our results demonstrate that IgM-expressing plasma cells can sense antigen and acquire competence for cytokine production upon antigenic challenge., Plasma cells produce secreted antibodies and are thought to lack expression of the membrane-bound immunoglobulins that constitute B-cell receptors. Here the authors show that IgM-expressing plasma cells maintain B-cell receptor expression and initiate cytokine production following antigen stimulation.
Published: 2016

45. Sofosbuvir-based treatment of hepatitis C with severe fibrosis (METAVIR F3/F4) after liver transplantation results from the CO23 ANRS CUPILT study

Author: Dumortier, Jerome, Leroy, V., Duvoux, C., Lédinghen, V., Francoz, C., Houssel-Debry, P., Radenne, S., d'Alteroche, L., Fougerou-Leurent, C., Canva, V., Martino, V., Conti, F., Kamar, Nassim, Moreno, C., Lebray, P., Tran, A., Besch, C., Diallo, A., Rohel, A., Rossignol, E., Abergel, A., Botta-Fridlund, D., Coilly, A., Samuel, D., Duclos-Vallée, J.-C., Pageaux, G.-P., Département d'hépatologie, Hospices Civils de Lyon (HCL), Epidémiologie pronostique des cancers et affections graves, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépatologie, Hôpital Henri Mondor, AP-HP, Créteil, France., Hôpital Henri Mondor, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Services de Maladies de l'Appareil Digestif, Hôpital Claude Huriez, Centre Hospitalier Universitaire de Lille, Lille, France, Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille, Service d'Hépatologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Service de Transplantation, Centre Hospitalier Universitaire de Strasbourg, Centre Hospitalier Universitaire de Strasbourg (CHU de Strasbourg ), Unité de la recherche fondamentale et clinique sur l' hépatite virale, France Recherche Nord & Sud Asdi-VIH Hépatites, Agence Nationale de Recherche sur le Sida, Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Image Science for Interventional Techniques (ISIT), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Centre National de la Recherche Scientifique (CNRS), Service d'hépato-gastroentérologie, Hôpital de la Conception, AP-HM, Marseille, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Paul Brousse, Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), National Agency for Research on Acquired Immune Deficiency Syndrome and Viral Hepatitis, Agence Nationale de Recherche sur le Sida, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Multiorgan Transplantation, CHU Toulouse [Toulouse], Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Paul Brousse-Université Paris-Sud - Paris 11 (UP11), Université de Montpellier (UM)-CHU Saint-Eloi, Jonchère, Laurent, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [SDV] Life Sciences [q-bio], hepatitis C virus, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, treatment, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, [SDV]Life Sciences [q-bio], [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, severe fibrosis (METAVIR F3/F4), [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, sofosbuvir-based, transplantation
Abstract: International audience; Recurrence of hepatitis C virus (HCV) after liver transplantation (LT) can rapidly lead to liver graft cirrhosis and, therefore, graft failure and retransplantation or death. The aim of the present study was to assess efficacy and tolerance of sofosbuvir (SOF)–based regimens for the treatment of HCV recurrence in patients with severe fibrosis after LT. The Compassionate Use of Protease Inhibitors in Viral C Liver Transplantation (CULPIT) study is a prospective multicenter cohort including patients with HCV recurrence following LT treated with second generation direct antivirals. The present study focused on patients included between October 2013 and November 2014 and diagnosed with HCV recurrence and liver graft extensive fibrosis (METAVIR F3/F4). A SOF-based regimen was administered to 125 patients fulfilling inclusion criteria. The median delay from LT was 95.9 ± 69.6 months. The characteristics of patients were as follows: mean age, 59.4 ± 9.0 years; 78.4% male; infected by HCV genotype 1: 78.2%, mean HCV RNA: 6.1 ± 1.0 log10 IU/mL. Eighty patients had failed previous post-LT antiviral therapy (64.0%) including triple therapy with first generation protease inhibitors in 19 (15.2%) patients. The main combination regimen was SOF/daclatasvir (73.6%). Ribavirin was used in 60 patients. Sustained virological response 12 weeks after treatment was 92.8% (on an intention-to-treat basis); 7 patients with virological failure were observed. Serious adverse events occurred in 25.6% of the patients during antiviral treatment. During antiviral treatment and follow-up, 3 patients were retransplanted and 4 patients died. In conclusion, SOF-based antiviral treatment shows very promising results in patients with HCV recurrence and severe fibrosis after LT. Liver Transplantation 22 1367–1378 2016 AASLD. © 2016 by the American Association for the Study of Liver Diseases
Published: 2016

46. Serum Iron Protects from Renal Postischemic Injury

Author: Claire Berrou, Laurent Mesnard, Marie Matignon, Thiago Trovati Maciel, Mariane Tami Amano, Martin Flamant, Sanae Ben Mkaddem, Pamella Huey Mei Wang, Ivan C. Moura, Carole Peyssonnaux, Yelena Ginzburg, François Vrtovsnik, Aurélie Fricot, Jacques Mathieu, Marie-Noëlle Peraldi, Marc Benhamou, Renato C. Monteiro, Carole Beaumont, Damien Grapton, Niels Olsen Saraiva Camara, Jonathan M. Chemouny, Celine Vaugier, Michael Dussiot, Eric Daugas, Olivier Hermine, Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Galilée, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Angiogénèse embryonnaire et pathologique, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Labex MemoLife, Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de transplantation rénale, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Department of Physiology and Biophysics, Cornell University [New York], UMR 1599, Centre National de la Recherche Scientifique (CNRS), Service de Néphrologie [Bichat - Claude Bernard], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Physiologie [Bichat-Claude Bernard], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre interdisciplinaire de recherche en biologie (CIRB), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Labex MemoLife, Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Cornell University, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Université de Franche-Comté (UFC)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC)
Subjects: 0301 basic medicine, Male, MACRÓFAGOS, medicine.disease_cause, Kidney, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Antioxidants, Monocytes, Mice, 0302 clinical medicine, Blood serum, ComputingMilieux_MISCELLANEOUS, biology, medicine.diagnostic_test, General Medicine, Middle Aged, Allografts, Prognosis, 3. Good health, medicine.anatomical_structure, Nephrology, 030220 oncology & carcinogenesis, Reperfusion Injury, Serum iron, Female, medicine.symptom, Glomerular Filtration Rate, Signal Transduction, Adult, medicine.medical_specialty, NF-E2-Related Factor 2, Iron, Inflammation, Peritonitis, Proinflammatory cytokine, 03 medical and health sciences, Internal medicine, medicine, Animals, Humans, business.industry, Macrophages, Kidney Transplantation, Transplantation, Ferritin, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, Basic Research, Ferritins, biology.protein, business, Reactive Oxygen Species, Oxidative stress
Abstract: Renal transplants remain a medical challenge, because the parameters governing allograft outcome are incompletely identified. Here, we investigated the role of serum iron in the sterile inflammation that follows kidney ischemia-reperfusion injury. In a retrospective cohort study of renal allograft recipients (n=169), increased baseline levels of serum ferritin reliably predicted a positive outcome for allografts, particularly in elderly patients. In mice, systemic iron overload protected against renal ischemia-reperfusion injury-associated sterile inflammation. Furthermore, chronic iron injection in mice prevented macrophage recruitment after inflammatory stimuli. Macrophages cultured in high-iron conditions had reduced responses to Toll-like receptor-2, -3, and -4 agonists, which associated with decreased reactive oxygen species production, increased nuclear localization of the NRF2 transcription factor, increased expression of the NRF2-related antioxidant response genes, and limited NF-κB and proinflammatory signaling. In macrophage-depleted animals, the infusion of macrophages cultured in high-iron conditions did not reconstitute AKI after ischemia-reperfusion, whereas macrophages cultured in physiologic iron conditions did. These findings identify serum iron as a critical protective factor in renal allograft outcome. Increasing serum iron levels in patients may thus improve prognosis of renal transplants.
Published: 2016

47. Generation of Catalytic Antibodies Is an Intrinsic Property of an Individual’s Immune System: A Study on a Large Cohort of Renal Transplant Patients

Author: Séverine Padiolleau-Lefèvre, Meenu Sharma, Ankit Mahendra, Didier Boquet, Ivan Peyron, Sébastien Lacroix-Desmazes, Laurent Gilardin, Bharath Wootla, Olivier Thaunat, Abhijit More, Srini V. Kaveri, Navin Varadarajan, Cécile Dollinger, Christophe Legendre, Desirazu N. Rao, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Department of Neurology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Indian Institute of Science, Génie Enzymatique et Cellulaire (GEC), Université de Technologie de Compiègne (UTC)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Ingénierie des Anticorps pour la Santé (LIAS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University of Houston, Service de néphrologie adultes [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Necker - Enfants Malades [AP-HP], Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Etudes et de Recherches en Immunoanalyses (LERI), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Médicaments et Technologies pour la Santé (MTS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Génie Enzymatique et Cellulaire ( GEC ), Université de Technologie de Compiègne ( UTC ) -Université de Picardie Jules Verne ( UPJV ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'Etudes et de Recherches en Immunoanalyses ( LERI ), Service de Pharmacologie et Immunoanalyse ( SPI ), Département Médicaments et Technologies pour la Santé ( DMTS ), Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Département Médicaments et Technologies pour la Santé ( DMTS ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), École pratique des hautes études (EPHE), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Médicaments et Technologies pour la Santé (MTS), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Graft Rejection, Male, 0301 basic medicine, [SDV]Life Sciences [q-bio], Antibodies, Catalytic, Disease, Biochemistry, Immunoglobulin G, 0302 clinical medicine, Immunology and Allergy, Medicine, Kidney transplantation, Aged, 80 and over, biology, Middle Aged, 3. Good health, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Antibody, Adult, Immunology, Article, Young Adult, 03 medical and health sciences, Immune system, Humans, Blood Coagulation, Pathological, Aged, Autoantibodies, Factor VIII, [ SDV ] Life Sciences [q-bio], business.industry, Autoantibody, medicine.disease, Kidney Transplantation, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Transplant Recipients, Transplantation, 030104 developmental biology, Immune System, Chronic Disease, biology.protein, business, Biomarkers, Follow-Up Studies, 030215 immunology
Abstract: The origin and physiopathological relevance of catalytic antibodies is not well understood owing to the fact that catalytic antibodies have been studied in relatively small cohorts of patients with rare diseases and/or without systematic follow-up. In the present study, we have followed the evolution of the levels of catalytic IgG in a large cohort of 100 renal transplant patients over a 2-year period. Prior to transplant, hydrolysis of the generic substrate PFR-MCA was greater for patients’ IgG than for a therapeutic preparation of pooled IgG from healthy donors (6.6±0.9 vs 0.65±0.03 fmol/min per pmol). Renal transplant was marked by a drastic decrease in levels of catalytic IgG over 3 months (6.6±0.9 vs 2.4±0.2 fmol/min/pmol; P
Published: 2016

48. A new protoparvovirus in human fecal samples and cutaneous T cell lymphomas (mycosis fungoides)

Author: Kathleen A. Alexander, Tung Gia Phan, Xutao Deng, Beatrix Kapusinszky, Patricia A. Pesavento, Eric Delwart, Jacques Dantal, Anne-Chantal Knol, Juliana D. Siqueira, Antonio Charlys da Costa, Patrícia Puccinelli Orlandi, Brigitte Dréno, Linlin Li, Franck Halary, Department of Laboratory Medicine [San Francisco], University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Blood Systems Research Institute, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de dermatologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institute of Tropical Medicine [Antwerp] (ITM), Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), Instituto Nacional de Cancer, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de Transplantation, Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Nephrologie, Virginia Tech [Blacksburg], CARACAL, Department of Pathology Microbiology and Immunology, University of California (UC), Bernardo, Elizabeth, University of California [San Francisco] (UCSF), University of California-University of California, and University of California
Subjects: 0301 basic medicine, T cell, Biopsy, RNA Splicing, [SDV.CAN]Life Sciences [q-bio]/Cancer, In situ hybridization, Protoparvovirus, Parvoviridae Infections, Parvovirus, 03 medical and health sciences, Feces, Open Reading Frames, CTCL, Mycosis Fungoides, [SDV.CAN] Life Sciences [q-bio]/Cancer, Virology, medicine, Humans, Oncolytic, Phylogeny, Mycosis fungoides, biology, medicine.diagnostic_test, biology.organism_classification, medicine.disease, 3. Good health, Lymphoma, Diarrhea, 030104 developmental biology, medicine.anatomical_structure, DNA, Viral, Metagenome, Cutavirus, Metagenomics, medicine.symptom, Skin Carcinoma
Abstract: International audience; We genetically characterized seven nearly complete genomes in the protoparvovirus genus from the feces of children with diarrhea. The viruses, provisionally named cutaviruses (CutaV), varied by 1–6% nucleotides and shared $ 76% and $ 82% amino acid identity with the NS1 and VP1 of human bufa-viruses, their closest relatives. Using PCR, cutavirus DNA was found in 1.6% (4/245) and 1% (1/100) of diarrhea samples from Brazil and Botswana respectively. In silico analysis of pre-existing metagenomics datasets then revealed closely related parvovirus genomes in skin biopsies from patients with epi-dermotropic cutaneous T-cell lymphoma (CTCL or mycosis fungoides). PCR of skin biopsies yielded cu-tavirus DNA in 4/17 CTCL, 0/10 skin carcinoma, and 0/21 normal or noncancerous skin biopsies. In situ hybridization of CTCL skin biopsies detected viral genome within rare individual cells in regions of neoplastic infiltrations. The influence of cutavirus infection on human enteric functions and possible oncolytic role in CTCL progression remain to be determined.
Published: 2016

49. CD1d-restricted peripheral T cell lymphoma in mice and humans

Author: Olivier Hermine, Philippe Gaulard, Paul Mondière, Martine Ffrench, Thierry Defrance, Mitchell Kronenberg, Tayla Heavican, Laurent Genestier, Archana Khurana, Rémy Robinot, Alexandra Traverse-Glehen, Marco Herling, Thierry Lamy, Nadine Martin, Emmanuel Bachy, Javeed Iqbal, Mikael Roussel, Mirjam Urb, Gabriel Bricard, Lucile Baseggio, Shilpi Chandra, Simon de Bernard, Laurent Buffat, Patrice N. Marche, Gilles Salles, Vahid Asnafi, Joël Lachuer, Alexandra Schrader, Olivier Blond, Stéphane Dalle, Olivier Thaunat, Sophie Gazzo, Giuliano Crispatzu, Morgan Taillardet, Magali Le Garff-Tavernier, Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), La Jolla Institute for Immunology [La Jolla, CA, États-Unis], AltraBio [Lyon], Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Nebraska Medical Center, University of Nebraska System, Laboratoire d'Hématologie Cellulaire, Hospices Civils de Lyon (HCL), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), University of Cologne, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de référence des mastocytoses (CEREMAST), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie Adulte, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Hematologie, CHU Pontchaillou [Rennes], Microenvironnement et cancer (MiCa), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale, Association Instituts Carnot, HE-3553/4-1, Deutsche Forschungsgemeinschaft, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), La Jolla Institute for Allergy and Immunology (LIA), La Jolla Institute for Allergy & Immunology, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de référence des mastocytoses, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Centre International de Recherche en Infectiologie ( CIRI ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Biologie Moléculaire de la Cellule ( LBMC ), Service d'Anatomie Pathologique, Institut d'oncologie/développement Albert Bonniot de Grenoble ( INSERM U823 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Transplantation Rénale et d'Immunologie Clinique, Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Université de Lyon, Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Necker Enfants-Malades (INEM) ( INEM - UM 111 (UMR 8253 / U1151) ), Microenvironnement et cancer ( MiCa ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Department of Pathology and Microbiology, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Service d'hématologie, Hospices Civils de Lyon, Centre National de la Recherche Scientifique (CNRS) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Claude Bernard Lyon 1 (UCBL) - École normale supérieure - Lyon (ENS Lyon), S P Jain School of Global Management (.) (SPJ), Laboratoire d'anatomie et de cytopathologie - Centre hospitalier Lyon Sud, École normale supérieure - Lyon (ENS Lyon) - Université Claude Bernard Lyon 1 (UCBL) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Institut d'oncologie/développement Albert Bonniot de Grenoble, Université Joseph Fourier - Grenoble 1 (UJF) - CHU Grenoble - EFS - Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physique des Particules de Marseille (CPPM), Université de la Méditerranée - Aix-Marseille 2 - Aix Marseille Université (AMU) - Centre National de la Recherche Scientifique (CNRS) - Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Universität zu Lübeck [Lübeck], Centre National de la Recherche Scientifique (CNRS) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Claude Bernard Lyon 1 (UCBL) - Centre Léon Bérard [Lyon], Université Paris Diderot - Paris 7 (UPD7) - École pratique des hautes études (EPHE) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Radio-Oncologie [Lyon], Hospices Civils de Lyon - Centre Hospitalier Lyon Sud [Pierre Bénite], Institut Imagine (UMR 1163), Laboratory of Cellular and Molecular Mechanisms of Hemathological Disorders and Therapeutic Implication, Institut Necker Enfants-Malades (INEM), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole), Université de Rennes 1 (UR1) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut d'écologie et des sciences de l'environnement de Paris (IEES), Centre National de la Recherche Scientifique (CNRS) - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12) - Université Pierre et Marie Curie - Paris 6 (UPMC) - Institut National de la Recherche Agronomique (INRA), Institut Albert Bonniot, Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12) - IFR10, and Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: Male, 0301 basic medicine, T cell, [SDV]Life Sciences [q-bio], Immunology, Receptors, Antigen, T-Cell, chemical and pharmacologic phenomena, Article, Mice, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Antigen, Blocking antibody, medicine, Animals, Antigens, Ly, Humans, Immunology and Allergy, ComputingMilieux_MISCELLANEOUS, Research Articles, Mice, Knockout, [ SDV ] Life Sciences [q-bio], biology, Lymphoma, T-Cell, Peripheral, hemic and immune systems, Natural killer T cell, medicine.disease, Peripheral T-cell lymphoma, 3. Good health, Lymphoma, [SDV] Life Sciences [q-bio], Streptococcus pneumoniae, 030104 developmental biology, medicine.anatomical_structure, CD1D, biology.protein, Female, Antigens, CD1d, Tumor Suppressor Protein p53, Antibody, NK Cell Lectin-Like Receptor Subfamily B, Signal Transduction
Abstract: Genestier et al. shed light on the cellular origin of peripheral T cell lymphoma (PTCL), showing that in both mice and humans, unconventional CD1d-restricted T cells may give rise to PTCL., Peripheral T cell lymphomas (PTCLs) are a heterogeneous entity of neoplasms with poor prognosis, lack of effective therapies, and a largely unknown pathophysiology. Identifying the mechanism of lymphomagenesis and cell-of-origin from which PTCLs arise is crucial for the development of efficient treatment strategies. In addition to the well-described thymic lymphomas, we found that p53-deficient mice also developed mature PTCLs that did not originate from conventional T cells but from CD1d-restricted NKT cells. PTCLs showed phenotypic features of activated NKT cells, such as PD-1 up-regulation and loss of NK1.1 expression. Injections of heat-killed Streptococcus pneumonia, known to express glycolipid antigens activating NKT cells, increased the incidence of these PTCLs, whereas Escherichia coli injection did not. Gene expression profile analyses indicated a significant down-regulation of genes in the TCR signaling pathway in PTCL, a common feature of chronically activated T cells. Targeting TCR signaling pathway in lymphoma cells, either with cyclosporine A or anti-CD1d blocking antibody, prolonged mice survival. Importantly, we identified human CD1d-restricted lymphoma cells within Vδ1 TCR-expressing PTCL. These results define a new subtype of PTCL and pave the way for the development of blocking anti-CD1d antibody for therapeutic purposes in humans.
Published: 2016

50. Non-Complement-Binding De Novo Donor-Specific Anti-HLA Antibodies and Kidney Allograft Survival

Author: Peter Nickerson, Pierre Merville, Florent Guerville, Sébastien Lepreux, Valérie Dubois, Olivier Thaunat, Chris Wiebe, Jean-Luc Taupin, Jonathan Visentin, Thomas Bachelet, Gwendaline Guidicelli, Emmanuel Morelon, Lionel Couzi, Service d'immunologie et d'immunogénétique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Service de Néphrologie-Transplantation-Dialyse, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, CHU Bordeaux [Bordeaux], University of Manitoba [Winnipeg], Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Transplantation, Néphrologie et Immunologie Clinique [Hôpital Edouard Herriot, HCL], Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Etablissement français du sang- Rhône-Alpes [Lyon], Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, 030232 urology & nephrology, 030230 surgery, urologic and male genital diseases, Gastroenterology, 0302 clinical medicine, immune system diseases, HLA Antigens, Antibody Specificity, Risk Factors, complement, Kidney transplantation, Kidney, biology, Graft Survival, General Medicine, Middle Aged, Allografts, de novo donor specific antibodies, Tissue Donors, 3. Good health, medicine.anatomical_structure, Nephrology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Antibody, Protein Binding, Adult, medicine.medical_specialty, chemical and pharmacologic phenomena, Human leukocyte antigen, Antibodies, 03 medical and health sciences, Antigen, Clinical Research, Internal medicine, medicine, Humans, Clinical significance, C1q, Retrospective Studies, business.industry, Complement System Proteins, medicine.disease, Kidney Transplantation, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Transplantation, body regions, biology.protein, Graft survival, business
Abstract: International audience; C1q-binding ability may indicate the clinical relevance of de novo donor-specific anti-HLA antibodies (DSA). This study investigated the incidence and risk factors for the appearance of C1q-binding de novo DSA and their long-term impact. Using Luminex Single Antigen Flow Bead assays, 346 pretransplant nonsensitized kidney recipients were screened at 2 and 5 years after transplantation for de novo DSA, which was followed when positive by a C1q Luminex assay. At 2 and 5 years, 12 (3.5%) and eight (2.5%) patients, respectively, had C1q-binding de novo DSA. De novo DSA mean fluorescence intensity \textgreater6237 and \textgreater10,000 at 2 and 5 years, respectively, predicted C1q binding. HLA mismatches and cyclosporine A were independently associated with increased risk of C1q-binding de novo DSA. When de novo DSA were analyzed at 2 years, the 5-year death-censored graft survival was similar between patients with C1q-nonbinding de novo DSA and those without de novo DSA, but was lower for patients with C1q-binding de novo DSA (P=0.003). When de novo DSA were analyzed at 2 and 5 years, the 10-year death-censored graft survival was lower for patients with C1q-nonbinding de novo DSA detected at both 2 and 5 years (P\textless0.001) and for patients with C1q-binding de novo DSA (P=0.002) than for patients without de novo DSA. These results were partially confirmed in two validation cohorts. In conclusion, C1q-binding de novo DSA are associated with graft loss occurring quickly after their appearance. However, the long-term persistence of C1q-nonbinding de novo DSA could lead to lower graft survival.
Published: 2016

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