100 results on '"Alain Le Moine"'
Search Results
2. BK Polyomavirus in Pediatric Renal Transplantation—What We Know and What We Do Not
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Benedetta Chiodini, Pauline Guillaume-Gentil, Charlotte Vanhomwegen, Elise Hennaut, Ksenija Lolin, Nathalie Tram, Alain Le Moine, and Khalid Ismaili
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BK polyomavirus ,BKPyV nephropathy ,kidney transplantation ,Biology (General) ,QH301-705.5 - Abstract
BK polyomavirus (BKPyV) is still a real threat in the management of kidney transplantation. Immunosuppressive treatment disrupts the equilibrium between virus replication and immune response, and uncontrolled BKPyV replication leads to nephropathy (BKPyV nephropathy). The first evidence of BKPyV reactivation in transplant recipients is the detection of viral shedding in urine, which appears in 20% to 60% of patients, followed by BKPyV viremia in 10–20% of kidney transplant recipients. BKPyV nephropathy eventually occurs in 1–10% of this population, mainly within the first 2 years post-transplantation, causing graft loss in about half of those patients. Few data exist regarding the pediatric population and we focus on them. In this paper, we review the existing diagnostic methods and summarize the evidence on the role of BKPyV humoral and cellular immunity in modulating the clinical course of BKPyV infection and as potential predictors of the outcome. We look at the known risk factors for BKPyV nephropathy in the immunosuppressed patient. Finally, we propose a sensible clinical attitude in order to screen and manage BKPyV infection in kidney transplant children.
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- 2024
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3. Case Report: Homozygous Pathogenic Variant P209L in the TTC21B Gene: A Rare Cause of End Stage Renal Disease and Biliary Cirrhosis Requiring Combined Liver-Kidney Transplantation. A Case Report and Literature Review
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Giuseppe Gambino, Concetta Catalano, Martina Marangoni, Caroline Geers, Alain Le Moine, Nathalie Boon, Guillaume Smits, and Lidia Ghisdal
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ciliopathies ,TTC21B ,clinical exome ,end stage renal disease (ESRD) ,biliary cirrhosis ,combined liver and kidney transplant ,Medicine (General) ,R5-920 - Abstract
Background: Ciliopathies are rare diseases causing renal and extrarenal manifestations. Here, we report the case of a ciliopathy induced by a homozygous pathogenic variant in the TTC21B gene.Case Description: A 47-year-old patient started hemodialysis for chronic kidney disease (CKD) of unknown origin. She presented with early onset of hypertension, pre-eclampsia, myopia and cirrhosis. Renal biopsy showed mild interstitial fibrosis, tubular atrophy, and moderate arteriosclerosis while liver pathology demonstrates grade B biliary cirrhosis. Family history revealed several cases of early-onset severe hypertension and one case of end-stage renal disease (ESRD) needing kidney transplantation at twenty years of age. Clinical exome sequencing showed homozygosis for the pathogenic variant c.626C>T (p.Pro209Leu) in the TTC21B gene. The patient underwent combined liver-renal transplantation with an excellent renal and hepatic graft outcome.Conclusions:TTC21B gene mutations can lead heterogeneous to clinical manifestations and represent an underappreciated cause of ESRD. The paradigm in diagnosis of CKD of early onset and/or of unknown origin is changing and genetic counseling should be performed in all patients and families that meet those criteria. Renal or combined liver-renal transplantation represents the best option for patients suffering from those diseases in terms of prognosis and quality of life.
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- 2021
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4. Donor-Derived Myeloid Heme Oxygenase-1 Controls the Development of Graft-Versus-Host Disease
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Chloé Spilleboudt, Virginie De Wilde, Philippe Lewalle, Ludovic Cabanne, Mathieu Leclerc, Florence Beckerich, Dominique Bories, Silvia Cardoso, Miguel P. Soares, Benoît Vokaer, Jean-Michel Hougardy, Véronique Flamand, Judith Racapé, Marc Abramowicz, Sébastien Maury, and Alain Le Moine
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Heme oxygenase-1 ,graft-versus-host disease ,transplantation ,hematopoeietic stem cell transplantation ,polymorphism ,myeloid-derived suppressor cells ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Graft-versus-host disease (GVHD) remains a major clinical drawback of allogeneic hematopoietic stem cell transplantation (HSCT). Here, we investigated how the stress responsive heme catabolizing enzyme heme oxygenase-1 (HO-1, encoded by HMOX1) regulates GVHD in response to allogeneic hematopoietic stem cell transplantation in mice and humans. We found that deletion of the Hmox1 allele, specifically in the myeloid compartment of mouse donor bone marrow, promotes the development of aggressive GVHD after allogeneic transplantation. The mechanism driving GVHD in mice transplanted with allogeneic bone marrow lacking HO-1 expression in the myeloid compartment involves enhanced T cell alloreactivity. The clinical relevance of these observations was validated in two independent cohorts of HSCT patients. Individuals transplanted with hematopoietic stem cells from donors carrying a long homozygous (GT)n repeat polymorphism (L/L) in the HMOX1 promoter, which is associated with lower HO-1 expression, were at higher risk of developing severe acute GVHD as compared to donors carrying a short (GT)n repeat (S/L or S/S) polymorphism associated with higher HO-1 expression. In this study, we showed the unique importance of donor-derived myeloid HO-1 in the prevention of lethal experimental GVHD and we corroborated this observation by demonstrating the association between human HMOX1 (GT)n microsatellite polymorphisms and the incidence of severe acute GVHD in two independent HSCT patient cohorts. Donor-derived myeloid HO-1 constitutes a potential therapeutic target for HSCT patients and large-scale prospective studies in HSCT patients are necessary to validate the HO-1 L/L genotype as an independent risk factor for developing severe acute GVHD.
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- 2021
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5. Specific expression of heme oxygenase-1 by myeloid cells modulates renal ischemia-reperfusion injury
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Maxime Rossi, Antoine Thierry, Sandrine Delbauve, Nicolas Preyat, Miguel P. Soares, Thierry Roumeguère, Oberdan Leo, Véronique Flamand, Alain Le Moine, and Jean-Michel Hougardy
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Medicine ,Science - Abstract
Abstract Renal ischemia-reperfusion injury (IRI) is a major risk factor for delayed graft function in renal transplantation. Compelling evidence exists that the stress-responsive enzyme, heme oxygenase-1 (HO-1) mediates protection against IRI. However, the role of myeloid HO-1 during IRI remains poorly characterized. Mice with myeloid-restricted deletion of HO-1 (HO-1M-KO), littermate (LT), and wild-type (WT) mice were subjected to renal IRI or sham procedures and sacrificed after 24 hours or 7 days. In comparison to LT, HO-1M-KO exhibited significant renal histological damage, pro-inflammatory responses and oxidative stress 24 hours after reperfusion. HO-1M-KO mice also displayed impaired tubular repair and increased renal fibrosis 7 days after IRI. In WT mice, HO-1 induction with hemin specifically upregulated HO-1 within the CD11b+ F4/80lo subset of the renal myeloid cells. Prior administration of hemin to renal IRI was associated with significant increase of the renal HO-1+ CD11b+ F4/80lo myeloid cells in comparison to control mice. In contrast, this hemin-mediated protection was abolished in HO-1M-KO mice. In conclusion, myeloid HO-1 appears as a critical protective pathway against renal IRI and could be an interesting therapeutic target in renal transplantation.
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- 2017
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6. Delayed Graft Function in Kidney Transplants: Time Evolution, Role of Acute Rejection, Risk Factors, and Impact on Patient and Graft Outcome
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Martin Chaumont, Judith Racapé, Nilufer Broeders, Fadoua El Mountahi, Annick Massart, Thomas Baudoux, Jean-Michel Hougardy, Dimitri Mikhalsky, Anwar Hamade, Alain Le Moine, Daniel Abramowicz, and Pierre Vereerstraeten
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Surgery ,RD1-811 - Abstract
Background. Although numerous risk factors for delayed graft function (DGF) have been identified, the role of ischemia-reperfusion injury and acute rejection episodes (ARE) occurring during the DGF period is ill-defined and DGF impact on patient and graft outcome remains controversial. Methods. From 1983 to 2014, 1784 kidney-only transplantations from deceased donors were studied. Classical risk factors for DGF along with two novel ones, recipient’s perioperative saline loading and residual diuresis, were analyzed by logistic regression and receiver operating characteristic (ROC) curves. Results. Along with other risk factors, absence of perioperative saline loading increases acute rejection incidence (OR = 1.9 [1.2–2.9]). Moreover, we observed two novel risk factors for DGF: patient’s residual diuresis ≤500 mL/d (OR = 2.3 [1.6–3.5]) and absence of perioperative saline loading (OR = 3.3 [2.0–5.4]). Area under the curve of the ROC curve (0.77 [0.74–0.81]) shows an excellent discriminant power of our model, irrespective of rejection. DGF does not influence patient survival (P=0.54). However, graft survival is decreased only when rejection was associated with DGF (P
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- 2015
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7. The cholinergic anti-inflammatory pathway delays TLR-induced skin allograft rejection in mice: cholinergic pathway modulates alloreactivity.
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Claude Sadis, Sophie Detienne, Benoît Vokaer, Louis-Marie Charbonnier, Philippe Lemaître, Chloé Spilleboudt, Sandrine Delbauve, Carole Kubjak, Véronique Flamand, Kenneth A Field, Michel Goldman, Fleur S Benghiat, and Alain Le Moine
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Medicine ,Science - Abstract
Activation of innate immunity through Toll-like receptors (TLR) can abrogate transplantation tolerance by revealing hidden T cell alloreactivity. Separately, the cholinergic anti-inflammatory pathway has the capacity to dampen macrophage activation and cytokine release during endotoxemia and ischemia reperfusion injury. However, the relevance of the α7 nicotinic acetylcholine receptor (α7nAChR)-dependent anti-inflammatory pathway in the process of allograft rejection or maintenance of tolerance remains unknown. The aim of our study is to investigate whether the cholinergic pathway could impact T cell alloreactivity and transplant outcome in mice. For this purpose, we performed minor-mismatched skin allografts using donor/recipient combinations genetically deficient for the α7nAChR. Minor-mismatched skin grafts were not rejected unless the mice were housed in an environment with endogenous pathogen exposure or the graft was treated with direct application of imiquimod (a TLR7 ligand). The α7nAChR-deficient recipient mice showed accelerated rejection compared to wild type recipient mice under these conditions of TLR activation. The accelerated rejection was associated with enhanced IL-17 and IFN-γ production by alloreactive T cells. An α7nAChR-deficiency in the donor tissue facilitated allograft rejection but not in recipient mice. In addition, adoptive T cell transfer experiments in skin-grafted lymphopenic animals revealed a direct regulatory role for the α7nAChR on T cells. Taken together, our data demonstrate that the cholinergic pathway regulates alloreactivity and transplantation tolerance at multiple levels. One implication suggested by our work is that, in an organ transplant setting, deliberate α7nAChR stimulation of brain dead donors might be a valuable approach for preventing donor tissue inflammation prior to transplant.
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- 2013
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8. IL-17A mediates early post-transplant lesions after heterotopic trachea allotransplantation in Mice.
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Philippe H Lemaître, Benoît Vokaer, Louis-Marie Charbonnier, Yoichiro Iwakura, Marc Estenne, Michel Goldman, Oberdan Leo, Myriam Remmelink, and Alain Le Moine
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Medicine ,Science - Abstract
Primary graft dysfunction (PGD) and bronchiolitis obliterans (BO) are the leading causes of morbidity and mortality after lung transplantation. Reports from clinical and rodent models suggest the implication of IL-17A in either PGD or BO. We took advantage of the heterotopic trachea transplantation model in mice to study the direct role of IL-17A in post-transplant airway lesions. Across full MHC barrier, early lesions were controlled in IL-17A(-/-) or anti-IL17 treated recipients. In contrast, IL-17A deficiency did not prevent subsequent obliterative airway disease (OAD). Interestingly, this early protection occurred also in syngeneic grafts and was accompanied by a decrease in cellular stress, as attested by lower HSP70 mRNA levels, suggesting the involvement of IL-17A in ischemia-reperfusion injury (IRI). Furthermore, persistence of multipotent CK14(+) epithelial stem cells underlined allograft protection afforded by IL-17A deficiency or neutralisation. Recipient-derived γδ(+) and CD4(+) T cells were the major source of IL-17A. However, lesions still occurred in the absence of each subset, suggesting a high redundancy between the innate and adaptive IL-17A producing cells. Notably, a double depletion significantly diminished lesions. In conclusion, this work implicated IL-17A as mediator of early post-transplant airway lesions and could be considered as a potential therapeutic target in clinical transplantation.
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- 2013
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9. IL-17A and IL-2-expanded regulatory T cells cooperate to inhibit Th1-mediated rejection of MHC II disparate skin grafts.
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Benoît Vokaer, Louis-Marie Charbonnier, Philippe H Lemaître, Chloé Spilleboudt, and Alain Le Moine
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Medicine ,Science - Abstract
Several evidences suggest that regulatory T cells (Treg) promote Th17 differentiation. Based on this hypothesis, we tested the effect of IL-17A neutralization in a model of skin transplantation in which long-term graft survival depends on a strong in vivo Treg expansion induced by transient exogenous IL-2 administration. As expected, IL-2 supplementation prevented rejection of MHC class II disparate skin allografts but, surprisingly, not in IL-17A-deficient recipients. We attested that IL-17A was not required for IL-2-mediated Treg expansion, intragraft recruitment or suppressive capacities. Instead, IL-17A prevented allograft rejection by inhibiting Th1 alloreactivity independently of Tregs. Indeed, T-bet expression of naive alloreactive CD4+ T cells and the subsequent Th1 immune response was significantly enhanced in IL-17A deficient mice. Our results illustrate for the first time a protective role of IL-17A in CD4+-mediated allograft rejection process.
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- 2013
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10. Nicotine protects kidney from renal ischemia/reperfusion injury through the cholinergic anti-inflammatory pathway.
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Claude Sadis, Gwen Teske, Geurt Stokman, Carole Kubjak, Nike Claessen, Fabrice Moore, Patrizia Loi, Bilo Diallo, Luc Barvais, Michel Goldman, Sandrine Florquin, and Alain Le Moine
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Medicine ,Science - Abstract
Kidney ischemia/reperfusion injury (I/R) is characterized by renal dysfunction and tubular damages resulting from an early activation of innate immunity. Recently, nicotine administration has been shown to be a powerful inhibitor of a variety of innate immune responses, including LPS-induced toxaemia. This cholinergic anti-inflammatory pathway acts via the alpha7 nicotinic acetylcholine receptor (alpha7nAChR). Herein, we tested the potential protective effect of nicotine administration in a mouse model of renal I/R injury induced by bilateral clamping of kidney arteries. Renal function, tubular damages and inflammatory response were compared between control animals and mice receiving nicotine at the time of ischemia. Nicotine pretreatment protected mice from renal dysfunction in a dose-dependent manner and through the alpha7nAChR, as attested by the absence of protection in alpha7nAChR-deficient mice. Additionally, nicotine significantly reduced tubular damages, prevented neutrophil infiltration and decreased productions of the CXC-chemokine KC, TNF-alpha and the proinflammatory high-mobility group box 1 protein. Reduced tubular damage in nicotine pre-treated mice was associated with a decrease in tubular cell apoptosis and proliferative response as attested by the reduction of caspase-3 and Ki67 positive cells, respectively. All together, these data highlight that nicotine exerts a protective anti-inflammatory effect during kidney I/R through the cholinergic alpha7nAChR pathway. In addition, this could provide an opportunity to overcome the effect of surgical cholinergic denervation during kidney transplantation.
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- 2007
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11. Salt-losing tubulopathy worsening the prognosis of renal sarcoidosis
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Anis Abu Ayyach, Alain Le Moine, Louiza Kaci, Claire Royer-Chardon, Lidia Ghisdal, Martina Marangoni, Guillaume Smits, and Joëlle Nortier
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Nephrology - Published
- 2023
12. Humoral and cellular immune correlates of protection against COVID-19 in kidney transplant recipients
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Delphine Kemlin, Nicolas Gemander, Stéphanie Depickère, Véronique Olislagers, Daphnée Georges, Alexandra Waegemans, Pieter Pannus, Anne Lemy, Maria E. Goossens, Isabelle Desombere, Johan Michiels, Marylène Vandevenne, Leo Heyndrickx, Kevin K. Ariën, André Matagne, Margaret E. Ackerman, Alain Le Moine, and Arnaud Marchant
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Transplantation ,Immunology and Allergy ,Pharmacology (medical) ,Human medicine - Abstract
As solid organ recipients are at high risk of severe COVID-19 and respond poorly to primary SARS-CoV-2 mRNA vaccination, they have been prioritized for booster vaccination. However, an immunological correlate of protection has not been identified in this vulnerable population. We conducted a prospective monocentric cohort study of 65 kidney transplant recipients who received three doses of SARS-CoV-2 BNT162b2 mRNA vaccination. Associations between symptomatic breakthrough infection (BTI) and vaccine responses, patient demographic and clinical characteristics were explored. Symptomatic COVID-19 was diagnosed in 32% of kidney transplant recipients during a period of six months after the administration of the third vaccine dose. During this period, SARS-CoV-2 delta and omicron were the dominant variants in the general population. Univariate analyzes identified avidity of SARS-CoV-2 receptor binding domain (RBD) binding IgG, neutralizing antibodies and SARS-CoV-2 S2 domain-specific IFN-γ responses as correlates of protection against BTI. Some demographic and clinical parameters correlated with vaccine responses, but none correlated with the risk of BTI. In multivariate analysis, the risk of BTI was best predicted by neutralizing antibody and S2-specific IFN-γ responses, adjusting for age, graft function and mycophenolate mofetil use. In conclusion, both antibody and T cell responses predict the risk of BTI in kidney transplant recipients who received three doses of SARS-CoV-2 mRNA vaccine. T cell responses may help compensate for the suboptimal antibody response to vaccination in this vulnerable population.One Sentence SummaryAntibody and T cell responses to booster SARS-CoV-2 vaccination predict the risk of symptomatic breakthrough infection in kidney transplant recipients
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- 2023
13. Oxygenated versus standard cold perfusion preservation in kidney transplantation (COMPARE)
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Ina Jochmans, Aukje Brat, Lucy Davies, H Sijbrand Hofker, Fenna E M van de Leemkolk, Henri G D Leuvenink, Simon R Knight, Jacques Pirenne, Rutger J Ploeg, Daniel Abramowicz, Neal Banga, Frederike J Bemelman, Michiel GH Betjes, Richéal Burns, Virginia Chiocchia, Maarten HL Christiaans, Tom Darius, Jeroen de Jonge, Aiko PJ de Vries, Olivier Detry, Luuk B Hilbrands, Arjan WJ Hoksbergen, Volkert AL Huurman, Mirza M Idu, Daniel Jacobs-Tulleneers-Thevissen, Maria Kaisar, Nada Kanaan, Diederik Kimenai, Dirk Kuypers, Alain Le Moine, Carl Marshall, Nicolas Meurisse, Dimitri Mikhalski, Cyril Moers, Diethard Monbaliu, Willemijn N Nijboer, S Azam Nurmohamed, John O'Callaghan, Vassilios Papalois, Lissa Pipeleers, Paul PC Poyck, Isabel Quiroga, Caren Randon, Geert W Schurink, Marc Seelen, Laszlo Szabo, Raechel J Toorop, Marcel CG van de Poll, Michel FP van der Jagt, Steven Van Laecke, Arjan D van Zuilen, Laurent Weekers, Dirk Ysebaert, Basic (bio-) Medical Sciences, Surgery, Nephrology, AII - Inflammatory diseases, ACS - Atherosclerosis & ischemic syndromes, APH - Aging & Later Life, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service de chirurgie et transplantation abdominale, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, Groningen Institute for Organ Transplantation (GIOT), and ACS - Diabetes & metabolism
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Male ,030204 cardiovascular system & hematology ,surgery ,0302 clinical medicine ,HYPOTHERMIC MACHINE PERFUSION ,030212 general & internal medicine ,Kidney transplantation ,donor ,Kidney ,Hazard ratio ,Organ Preservation ,General Medicine ,Middle Aged ,3. Good health ,Cold Temperature ,Europe ,Perfusion ,medicine.anatomical_structure ,REJECTION ,Tissue and Organ Harvesting ,COMPARE Trial Collaboration and Consortium for Organ Preservation in Europe (COPE) ,Female ,Glomerular Filtration Rate ,STORAGE ,medicine.medical_specialty ,preservation ,Urology ,Renal function ,kidney transplantation ,03 medical and health sciences ,Double-Blind Method ,Immunology and Microbiology(all) ,medicine ,cold hypoxic condition ,Humans ,Tissue Survival ,Machine perfusion ,business.industry ,Oxygenation ,medicine.disease ,Kidney Transplantation ,Oxygen ,standard cold perfusion preservation ,Renal disorders Radboud Institute for Health Sciences [Radboudumc 11] ,business ,TERM GRAFT-SURVIVAL ,Kidney disease ,transplantation - Abstract
Contains fulltext : 229465.pdf (Publisher’s version ) (Closed access) BACKGROUND: Deceased donor kidneys are preserved in cold hypoxic conditions. Providing oxygen during preservation might improve post-transplant outcomes, particularly for kidneys subjected to greater degrees of preservation injury. This study aimed to investigate whether supplemental oxygen during hypothermic machine perfusion (HMP) could improve the outcome of kidneys donated after circulatory death. METHODS: This randomised, double-blind, paired, phase 3 trial was done in 19 European transplant centres. Kidney pairs from donors aged 50 years or older, donated after circulatory death, were eligible if both kidneys were transplanted into two different recipients. One kidney from each donor was randomly assigned using permuted blocks to oxygenated hypothermic machine perfusion (HMPO(2)), the other to HMP without oxygenation. Perfusion was maintained from organ retrieval to implantation. The primary outcome was 12-month estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration equation in pairs of donated kidneys in which both transplanted kidneys were functioning at the end of follow-up. Safety outcomes were reported for all transplanted kidneys. Intention-to-treat analyses were done. This trial is registered with the ISRCTN Registry, ISRCTN32967929, and is now closed. FINDINGS: Between March 15, 2015, and April 11, 2017, 197 kidney pairs were randomised with 106 pairs transplanted into eligible recipients. 23 kidney pairs were excluded from the primary analysis because of kidney failure or patient death. Mean eGFR at 12 months was 50·5 mL/min per 1·73 m(2) (SD 19·3) in the HMPO(2) group versus 46·7 mL/min per 1·73m(2) (17·1) in HMP (mean difference 3·7 mL/min per 1·73m(2), 95% CI -1·0 to 8·4; p=0·12). Fewer severe complications (Clavien-Dindo grade IIIb or more) were reported in the HMPO(2) group (46 of 417, 11%, 95% CI 8% to 14%) than in the HMP group (76 of 474, 16%, 13% to 20%; p=0·032). Graft failure was lower with HMPO(2) (three [3%] of 106) compared with HMP (11 [10%] of 106; hazard ratio 0·27, 95% CI 0·07 to 0·95; p=0·028). INTERPRETATION: HMPO(2) of kidneys donated after circulatory death is safe and reduces post-transplant complications (grade IIIb or more). The 12-month difference in eGFR between the HMPO(2) and HMP groups was not significant when both kidneys from the same donor were still functioning 1-year post-transplant, but potential beneficial effects of HMPO(2) were suggested by analysis of secondary outcomes. FUNDING: European Commission 7th Framework Programme.
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- 2020
14. Hybrid immunity to SARS‐CoV‐2 in kidney transplant recipients and hemodialysis patients
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Isabelle Desombere, Pieter Pannus, Delphine Kemlin, Anne Lemy, Maria E Goossens, Arnaud Marchant, Alain Le Moine, and Nicolas Gemander
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dialysis: hemodialysis ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,translational research/science ,medicine.medical_treatment ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,infectious disease ,kidney transplantation/nephrology ,clinical research/practice ,Kidney transplant ,Immunity ,Renal Dialysis ,vaccine ,Immunology and Allergy ,Medicine ,Humans ,Pharmacology (medical) ,Letters to the Editor ,Letter to the Editor ,immunobiology ,Transplantation ,business.industry ,SARS-CoV-2 ,COVID-19 ,Virology ,Kidney Transplantation ,Transplant Recipients ,Infectious disease (medical specialty) ,Hemodialysis ,business - Published
- 2021
15. Afucosylation of HLA-specific IgG1 as a potential predictor of antibody pathogenicity in kidney transplantation
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Pranay Bharadwaj, Sweta Shrestha, Tamas Pongracz, Catalano Concetta, Shilpee Sharma, Alain Le Moine, Noortje de Haan, Naoka Murakami, Leonardo V. Riella, Vanda Holovska, Manfred Wuhrer, Arnaud Marchant, and Margaret E. Ackerman
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General Biochemistry, Genetics and Molecular Biology - Abstract
SummaryAntibody-mediated rejection (AMR) is the leading cause of graft failure. While donor-specific antibodies (DSA) are associated with a higher risk of AMR, not all patients with DSA develop rejection suggesting that the characteristics of alloantibodies that determine their pathogenicity remain undefined. Using human leukocyte antigen (HLA)-A2-specific antibodies as a model, we applied systems serology tools to investigate qualitative features of immunoglobulin G (IgG) alloantibodies including Fc-glycosylation patterns and FcγR binding properties. The levels of afucosylation of anti-A2 antibodies were elevated in all seropositive patients and were significantly higher in AMR patients, suggesting potential cytotoxicity via FcγRIII-mediated mechanisms. Afucosylation of both glycoengineered monoclonal and naturally glycovariant polyclonal serum IgG specific to HLA-A2 exhibited potentiated binding to, slower dissociation from, and enhanced signaling through FcγRIII, a receptor widely expressed on innate effector cells. Collectively, these results suggest that afucosylated DSA may be a biomarker of AMR and could contribute to its pathogenesis. Graphical Abstract.Potential influence of HLA-A2-specific IgG1 afucosylation, FcγRIIIa binding and activation on ADCC and graft rejection.Illustration created with https://BioRender.com.
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- 2022
16. Does kidney transplantation with a standard or expanded criteria donor improve patient survival?
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Rachel Hellemans, Erwin de Vries, Dirk Kuypers, Jean-Marie Krzesinski, Michel Jadoul, Frederic Collart, Karl Martin Wissing, Kitty J Jager, Johan De Meester, Daniel Abramowicz, Steven Van Laecke, Ineke Tieken, Undine Samuel, Vianda S. Stel, Marieke van Meel, Serge Vogelaar, Anneke Kramer, Alain Le Moine, Kim Luyckx, Clinical sciences, Nephrology, Medical Informatics, ACS - Pulmonary hypertension & thrombosis, APH - Aging & Later Life, APH - Quality of Care, APH - Methodology, and APH - Global Health
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Male ,medicine.medical_treatment ,030232 urology & nephrology ,030230 surgery ,Expanded Criteria Donor ,Kidney ,Cohort Studies ,0302 clinical medicine ,Belgium ,Medicine and Health Sciences ,Medicine ,Kidney transplantation ,RISK ,OUTCOMES ,Néphrologie - urologie ,RENAL-TRANSPLANTATION ,Graft Survival ,DEATH ,ASSOCIATION ,Middle Aged ,Tissue Donors ,Nephrology ,Cohort ,DELAYED GRAFT ,Hemodialysis ,expanded criteria donor ,Adult ,medicine.medical_specialty ,kidney transplantation ,elderly ,survival ,03 medical and health sciences ,Renal Dialysis ,Internal medicine ,Diabetes mellitus ,Humans ,AcademicSubjects/MED00340 ,Dialysis ,Aged ,Retrospective Studies ,GRAFT-SURVIVAL ,OLDER ,Transplantation ,business.industry ,Original Articles ,QUANTIFICATION ,medicine.disease ,Survival Analysis ,Transplantation d'organes ,Confidence interval ,RECIPIENTS ,dialysis ,Human medicine ,business - Abstract
BACKGROUND: Changes in recipient and donor factors have reopened the question of survival benefits of kidney transplantation versus dialysis. METHODS: We analysed survival among 3808 adult Belgian patients waitlisted for a first deceased donor kidney transplant from 2000 to 2012. The primary outcome was mortality during the median waiting time plus 3 years of follow-up after transplantation or with continued dialysis. Outcomes were analysed separately for standard criteria donor (SCD) and expanded criteria donor (ECD) kidney transplants. We adjusted survival analyses for recipient age (20-44, 45-64 and ≥65 years), sex and diabetes as the primary renal disease. RESULTS: Among patients ≥65 years of age, only SCD transplantation provided a significant survival benefit compared with dialysis, with a mortality of 16.3% [95% confidence interval (CI) 13.2-19.9] with SCD transplantation, 20.5% (95% CI 16.1-24.6) with ECD transplantation and 24.6% (95% CI 19.4-29.5) with continued dialysis. Relative mortality risk was increased in the first months after transplantation compared with dialysis, with equivalent risk levels reached earlier with SCD than ECD transplantation in all age groups. CONCLUSIONS: The results of this study suggest that older patients might gain a survival benefit with SCD transplantation versus dialysis, but any survival benefit with ECD transplantation versus dialysis may be small., SCOPUS: ar.j, info:eu-repo/semantics/published
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- 2021
17. HO-1 mitigates acute kidney injury and subsequent kidney-lung cross-talk
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Maxime Rossi, Jean-Michel Hougardy, Oberdan Leo, Sandrine Delbauve, Thierry Roumeguere, Eric Wespes, Véronique Flamand, and Alain Le Moine
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word count ,Male ,0301 basic medicine ,medicine.medical_specialty ,Biochimie ,Heme Oxygenase-1 -- pharmacology -- therapeutic use ,Urology ,Kidney -- drug effects -- pathology ,Kidney ,urologic and male genital diseases ,Biochemistry ,Mice ,03 medical and health sciences ,Inflammation -- etiology ,Lung -- drug effects -- pathology ,medicine ,Animals ,Humans ,cardiovascular diseases ,hemin ,Lung ,Renal ischemia reperfusion ,renal ischemia-reperfusion ,Inflammation ,030102 biochemistry & molecular biology ,urogenital system ,business.industry ,fungi ,Acute kidney injury ,heme oxygenase-1 ,General Medicine ,Sciences bio-médicales et agricoles ,Acute Kidney Injury ,medicine.disease ,female genital diseases and pregnancy complications ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,acute lung injury ,cross-talk ,business ,Heme Oxygenase-1 ,Kidney disease - Abstract
Ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI), which contributes to the development of chronic kidney disease (CKD). IRI-induced AKI releases proinflammatory cytokines (e.g. IL-1β, TNF-α, IL-6) that induce a systemic inflammatory response, resulting in proinflammatory cells recruitment and remote organ damage. AKI is associated with poor outcomes, particularly when extrarenal complications or distant organ injuries occur. Acute lung injury (ALI) is a major remote organ dysfunction associated with AKI. Hence, kidney-lung cross-talk remains a clinical challenge, especially in critically ill population. The stress-responsive enzyme, heme oxygenase-1 (HO-1) is largely known to protect against renal IRI and may be preventively induced using hemin prior to renal insult. However, the use of hemin-induced HO-1 to prevent AKI-induced ALI remains poorly investigated. Mice received an intraperitoneal injection of hemin or sterile saline 1 day prior to surgery. Twenty-four hours later, mice underwent bilateral renal IRI for 26 min or sham surgery. After 4 or 24 h of reperfusion, mice were sacrificed. Hemin-induced HO-1 improved renal outcomes after IRI (i.e. fewer renal damage, renal inflammation, and oxidative stress). This protective effect was associated with a dampened systemic inflammation (i.e. IL-6 and KC). Subsequently, mitigated lung inflammation was found in hemin-treated mice (i.e. neutrophils influx and lung KC). The present study demonstrates that hemin-induced HO-1 controls the magnitude of renal IRI and the subsequent AKI-induced ALI. Therefore, targeting HO-1 represents a promising approach to prevent the impact of renal IRI on distant organs, such as lung., SCOPUS: ar.j, info:eu-repo/semantics/published
- Published
- 2019
18. Antibiotics versus no therapy in kidney transplant recipients with asymptomatic bacteriuria (BiRT): a pragmatic, multicentre, randomized, controlled trial
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Julien Coussement, Nassim Kamar, Marie Matignon, Laurent Weekers, Anne Scemla, Magali Giral, Judith Racapé, Éric Alamartine, Laurent Mesnard, Mireille Kianda, Lidia Ghisdal, Concetta Catalano, Emine N. Broeders, Olivier Denis, Karl M. Wissing, Marc Hazzan, Daniel Abramowicz, Audrey Beq, Tatiana Besse-Hammer, Marie-Noëlle Blondel-Halley, Arnaud Borsu, Vianney Charpy, Lionel Couzi, Frédéric Debelle, Arnaud del Bello, Marie de Solere, Sara Frade, Luc Frimat, Philippe Grimbert, Pierrick Guerif, Rachel Hellemans, Bénédicte Hodemon-Corne, Jean-Michel Hougardy, Alain Le Moine, Nicole Lietaer, Olivier Lortholary, Kirsty Loudon, Annick Massart, Els Meersman, Thavarak Ouk, Lissa Pipeleers, Sandrine Roisin, Sarah Tollot, Sabine Verhofstede, Martin Wojcik, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) (Inserm U955), 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), Centre Hospitalier Universitaire de Liège (CHU-Liège), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Ecole de Santé Publique [Université Libre de Bruxelles], Université libre de Bruxelles (ULB), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Centre Hospitalier Universitaire Brugmann [Bruxelles] (CHU), Université Catholique de Louvain = Catholic University of Louvain (UCL), Vrije Universiteit Brussel (VUB), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Universiteit Antwerpen = University of Antwerpen [Antwerpen], Hôpital de Rangueil, CHU Toulouse [Toulouse], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Urgences néphrologiques et transplantation rénale [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), Universiteit Antwerpen [Antwerpen], UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Pathologie infectieuse, Clinical sciences, Nephrology, Faculty of Medicine and Pharmacy, Service d'Urgences néphrologiques et transplantation rénale [CHU Tenon], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
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Male ,0301 basic medicine ,[SDV]Life Sciences [q-bio] ,Antibiotics ,urologic and male genital diseases ,law.invention ,Kidney transplantation ,0302 clinical medicine ,Randomized controlled trial ,Interquartile range ,law ,Essais, contrôle médicaments ,030212 general & internal medicine ,Urinary tract infection ,Néphrologie - urologie ,Pyelonephritis ,Incidence (epidemiology) ,Hazard ratio ,General Medicine ,Middle Aged ,Sciences bio-médicales et agricoles ,female genital diseases and pregnancy complications ,Anti-Bacterial Agents ,3. Good health ,surgical procedures, operative ,Infectious Diseases ,Nephrology ,Female ,Microbiology (medical) ,medicine.medical_specialty ,Bacteriuria ,medicine.drug_class ,Urinary system ,030106 microbiology ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Biology ,Aged ,Urinary tract ,business.industry ,bacterial infections and mycoses ,medicine.disease ,Transplantation d'organes ,Transplant Recipients ,Human medicine ,business ,Asymptomatic bacteriuria - Abstract
Many transplant physicians screen for and treat asymptomatic bacteriuria (ASB) during post-kidney-transplant surveillance. We investigated whether antibiotics are effective in reducing the occurrence of symptomatic urinary tract infection (UTI) in kidney transplant recipients with ASB., info:eu-repo/semantics/published
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- 2020
19. P1630IS THERE ALWAYS A SURVIVAL BENEFIT WITH KIDNEY TRANSPLANTATION? RESULTS FROM A BELGIAN COHORT
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Alain Le Moine, Ineke Tieken, Undine Samuel, Vianda S. Stel, Dirk Kuypers, Daniel Abramowicz, Wim Van Biesen, Kitty J. Jager, Rachel Hellemans, Jean-Marie Krzesinski, Karl Martin Wissing, Johan De Meester, Michel Jadoul, Kim Luyckx, Erwin de Vries, Marieke van Meel, Anneke Kramer, and Serge Vogelaar
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Transplantation ,medicine.medical_specialty ,Survival benefit ,Nephrology ,business.industry ,Internal medicine ,Cohort ,medicine ,business ,medicine.disease ,Kidney transplantation - Abstract
Background and Aims Older studies have shown a survival benefit with kidney transplantation compared to dialysis, even for patients older than 60 years. However, due to important evolutions such as older recipient age and the use of less-than-optimal quality donors, it is unclear if the survival benefit with transplantation still holds true nowadays. Method Patient survival was analyzed for 3808 Belgian patients waitlisted for a first deceased donor kidney transplant between 2000 to 2012. Patients were divided into age categories (20-44y, 45-64y, ≥65y). Primary outcome was the comparison of mortality during median waiting time plus 3 years follow-up, either after transplantation or when remaining on dialysis. Outcomes were analyzed separately for those receiving a standard criteria donor (SCD) or an expanded criteria donor (ECD) transplant. The survival analyses were adjusted for age, sex and primary renal disease. Results Among patients ≥ 65 years old, only SCD transplantation provided a significant survival benefit compared to dialysis: mortality was 16.3 % (95 % CI: 13.2–19.9 %) with SCD transplantation, 20.5 % (16.1–24.6 %) with ECD transplantation, and 24.6 % (19.5–29.5 %) when remaining on dialysis. Relative mortality risk was increased in the first months after transplantation compared to dialysis, with equal risk levels being reached earlier for SCD than ECD transplantations in all age groups. Conclusion This study suggests that older patients have a survival benefit with SCD transplantation versus dialysis, but the survival benefit with ECD transplantation versus dialysis may be small or non-existent.
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- 2020
20. Heme oxygenase-1 orchestrates the immunosuppressive program of tumor-associated macrophages
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Emmanuelle Alaluf, Stanislas Goriely, Aurélie Detavernier, Alice Carrette, Miguel P. Soares, Abdulkader Azouz, Louis Boon, Marion Splittgerber, Benoît Vokaer, Alain Le Moine, and Frédérick Libert
- Subjects
0301 basic medicine ,medicine.medical_treatment ,T cell ,Immunology ,Cancer immunotherapy ,Biology ,CD8-Positive T-Lymphocytes ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Neoplasms ,Immunologie ,Tumor-Associated Macrophages ,medicine ,Immune Tolerance ,Tumor Microenvironment ,Animals ,Heme ,Innate immunity ,Mice, Knockout ,Tumor microenvironment ,Innate immune system ,Macrophages ,Monocyte ,Membrane Proteins ,General Medicine ,Sciences bio-médicales et agricoles ,3. Good health ,Heme oxygenase ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,chemistry ,Tumor progression ,030220 oncology & carcinogenesis ,Cancer research ,Heme Oxygenase-1 ,Research Article - Abstract
Tumor-associated macrophages (TAMs) contribute to the maintenance of a strong immunosuppressive environment, supporting tumor progression and resistance to treatment. To date, the mechanisms that drive acquisition of these immunosuppressive features are still poorly defined. Heme oxygenase-1 (HO-1) is the rate-limiting enzyme that catabolizes free heme. It displays important cytoprotective, antiinflammatory, and antioxidant properties. A growing body of evidence suggests that HO-1 may also promote tumor development. Herein, we show that HO-1 is highly expressed in monocytic cells in the tumor microenvironment (TME) once they differentiate into TAMs. Deletion of HO-1 in the myeloid compartment enhances the beneficial effects of a therapeutic antitumor vaccine by restoring CD8+ T cell proliferation and cytotoxicity. We further show that induction of HO-1 plays a major role in monocyte education by tumor cells by modulating their transcriptional and epigenetic programs. These results identify HO-1 as a valuable therapeutic target to reprogram the TME and synergize with current cancer therapies to facilitate antitumor response., info:eu-repo/semantics/published
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- 2020
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21. Dual effect of hemin on renal ischemia-reperfusion injury
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Eric Wespes, Véronique Flamand, Jean-Michel Hougardy, Oberdan Leo, Maxime Rossi, Thierry Roumeguere, Sandrine Delbauve, and Alain Le Moine
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Male ,0301 basic medicine ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Biophysics ,Urology ,Inflammation ,Kidney ,urologic and male genital diseases ,medicine.disease_cause ,Biochemistry ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,polycyclic compounds ,medicine ,Animals ,Ischemic Preconditioning ,Molecular Biology ,Dose-Response Relationship, Drug ,urogenital system ,business.industry ,Acute kidney injury ,Sham surgery ,Membrane Proteins ,Cell Biology ,Acute Kidney Injury ,medicine.disease ,female genital diseases and pregnancy complications ,Nephrectomy ,Mice, Inbred C57BL ,Transplantation ,Oxidative Stress ,030104 developmental biology ,Gene Expression Regulation ,chemistry ,Reperfusion Injury ,030220 oncology & carcinogenesis ,Hemin ,medicine.symptom ,business ,Heme Oxygenase-1 ,Oxidative stress ,Kidney disease - Abstract
Acute kidney injury (AKI) is a major public health concern, which is contributing to serious hospital complications, chronic kidney disease (CKD) and even death. Renal ischemia-reperfusion injury (IRI) remains a leading cause of AKI. The stress-responsive enzyme, heme oxygenase-1 (HO-1) mediates protection against renal IRI and may be preventively induced using hemin prior to renal insult. This HO-1 induction pathway called hemin preconditioning is largely known to be effective. Therefore, HO-1 might be an interesting therapeutic target in case of predictable AKI (e.g. partial nephrectomy or renal transplantation). However, the use of hemin to mitigate established AKI remains poorly characterized. Mice underwent bilateral renal IRI for 26 min or sham surgery. After surgical procedure, animals were injected either with hemin (5 mg/kg) or vehicle. Twenty-four hours later, mice were sacrificed. Despite strong HO-1 induction, hemin-treated mice exhibited significant renal damage and oxidative stress as compared to vehicle-treated mice. Interestingly, higher dose of hemin is associated with more severe IRI-induced AKI in a dose-dependent relation. To determine whether hemin preconditioning remains efficient to dampen postoperative hemin-amplified IRI-induced AKI, we pretreated mice either with hemin (5 mg/kg) or vehicle 24 h prior to surgical procedure. Then, all mice (hemin- and vehicle-pretreated) received postoperative injection of hemin (5 mg/kg) to amplify IRI-induced AKI. In comparison to vehicle, prior administration of hemin to renal IRI mitigated hemin-amplified IRI-induced AKI as attested by fewer renal damage, inflammation and oxidative stress. In conclusion, hemin may have a dual effect on renal IRI, protective or deleterious, depending on the timing of its administration.
- Published
- 2018
22. What are the effects of everolimus and basiliximab on Treg regulation and tolerance after liver transplantation?
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Alain Le Moine
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Graft Rejection ,Oncology ,medicine.medical_specialty ,Everolimus ,Hepatology ,Basiliximab ,business.industry ,medicine.medical_treatment ,Gastroenterology ,MEDLINE ,Liver transplantation ,T-Lymphocytes, Regulatory ,Liver Transplantation ,Text mining ,Internal medicine ,medicine ,Humans ,business ,Immunosuppressive Agents ,medicine.drug - Published
- 2021
23. Specific expression of heme oxygenase-1 by myeloid cells modulates renal ischemia-reperfusion injury
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Alain Le Moine, Nicolas Preyat, Antoine Thierry, Miguel P. Soares, Jean-Michel Hougardy, Maxime Rossi, Oberdan Leo, Sandrine Delbauve, Véronique Flamand, Thierry Roumeguere, Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut de Biologie et Médecine Moléculaire, and Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM)
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0301 basic medicine ,Male ,Pathology ,Myeloid ,[SDV]Life Sciences [q-bio] ,Translational immunology ,medicine.disease_cause ,urologic and male genital diseases ,Gene Knockout Techniques ,Mice ,Medicine ,Myeloid Cells ,Cells, Cultured ,Multidisciplinary ,biology ,Acute kidney injury ,Sciences bio-médicales et agricoles ,3. Good health ,Up-Regulation ,medicine.anatomical_structure ,Integrin alpha M ,Reperfusion Injury ,Hemin ,Kidney Diseases ,medicine.medical_specialty ,Science ,Article ,03 medical and health sciences ,Internal medicine ,Renal fibrosis ,Animals ,Monocytes and macrophages ,business.industry ,Membrane Proteins ,medicine.disease ,Heme oxygenase ,Transplantation ,Disease Models, Animal ,Oxidative Stress ,030104 developmental biology ,Endocrinology ,biology.protein ,business ,Reperfusion injury ,Oxidative stress ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Heme Oxygenase-1 - Abstract
Renal ischemia-reperfusion injury (IRI) is a major risk factor for delayed graft function in renal transplantation. Compelling evidence exists that the stress-responsive enzyme, heme oxygenase-1 (HO-1) mediates protection against IRI. However, the role of myeloid HO-1 during IRI remains poorly characterized. Mice with myeloid-restricted deletion of HO-1 (HO-1(M-KO)), littermate (LT), and wild-type (WT) mice were subjected to renal IRI or sham procedures and sacrificed after 24 hours or 7 days. In comparison to LT, HO-1(M-KO) exhibited significant renal histological damage, pro-inflammatory responses and oxidative stress 24 hours after reperfusion. HO-1(M-KO) mice also displayed impaired tubular repair and increased renal fibrosis 7 days after IRI. In WT mice, HO-1 induction with hemin specifically upregulated HO-1 within the CD11b(+) F4/80(lo) subset of the renal myeloid cells. Prior administration of hemin to renal IRI was associated with significant increase of the renal HO-1(+) CD11b(+) F4/80(lo) myeloid cells in comparison to control mice. In contrast, this hemin-mediated protection was abolished in HO-1(M-KO) mice. In conclusion, myeloid HO-1 appears as a critical protective pathway against renal IRI and could be an interesting therapeutic target in renal transplantation., SCOPUS: ar.j, info:eu-repo/semantics/published
- Published
- 2017
24. Early acute microvascular kidney transplant rejection in the absence of anti-HLA antibodies is associated with preformed IgG antibodies against diverse glomerular endothelial cell antigens
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Olivier Thaunat, Nicolas Cagnard, Cyril Garrouste, Marc Hazzan, Christophe Mariat, Marion Rabant, Nadia Arzouk, Pierre Merville, Emmanuel Zorn, Jean Luc Taupin, Pierre François Westeel, Jean-Paul Duong Van Huyen, Carole Burger, Alain Le Moine, Philippe Gatault, Nassim Kamar, Olivier Alibeu, Dominique Bertrand, Simon C. Satchell, Sarah S.B. See, Sophie Caillard, Joseph Rivalan, Baptiste Lamarthée, Christophe Legendre, Marc Ladrière, Béatrice Charreau, Vincent Vuiblet, Magali Giral, Marie Matignon, Dany Anglicheau, Johnny Sayegh, Alexandre Hertig, Anne Cesbron, Sylvain Pagie, and Marianne Delville
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Adult ,Graft Rejection ,Male ,Vasculitis ,Thrombotic microangiopathy ,Time Factors ,Cell ,Kidney Glomerulus ,Bristol Heart Institute ,030232 urology & nephrology ,Hemorrhage ,030230 surgery ,Receptor, Angiotensin, Type 1 ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,Clinical Research ,Biopsy ,Medicine ,Humans ,Receptor ,Aged ,biology ,medicine.diagnostic_test ,Endothelin-1 ,business.industry ,Thrombotic Microangiopathies ,Endothelial Cells ,General Medicine ,Middle Aged ,medicine.disease ,Kidney Transplantation ,Transplantation ,medicine.anatomical_structure ,Nephrology ,Immunoglobulin G ,Immunology ,Acute Disease ,Microvessels ,biology.protein ,Female ,Antibody ,business - Abstract
BACKGROUND: Although anti-HLA antibodies (Abs) cause most antibody-mediated rejections of renal allografts, non-anti-HLA Abs have also been postulated to contribute. A better understanding of such Abs in rejection is needed.METHODS: We conducted a nationwide study to identify kidney transplant recipients without anti-HLA donor-specific Abs who experienced acute graft dysfunction within 3 months after transplantation and showed evidence of microvascular injury, called acute microvascular rejection (AMVR). We developed a crossmatch assay to assess serum reactivity to human microvascular endothelial cells, and used a combination of transcriptomic and proteomic approaches to identify non-HLA Abs.RESULTS: We identified a highly selected cohort of 38 patients with early acute AMVR. Biopsy specimens revealed intense microvascular inflammation and the presence of vasculitis (in 60.5%), interstitial hemorrhages (31.6%), or thrombotic microangiopathy (15.8%). Serum samples collected at the time of transplant showed that previously proposed anti-endothelial cell Abs-angiotensin type 1 receptor (AT1R), endothelin-1 type A and natural polyreactive Abs-did not increase significantly among patients with AMVR compared with a control group of stable kidney transplant recipients. However, 26% of the tested AMVR samples were positive for AT1R Abs when a threshold of 10 IU/ml was used. The crossmatch assay identified a common IgG response that was specifically directed against constitutively expressed antigens of microvascular glomerular cells in patients with AMVR. Transcriptomic and proteomic analyses identified new targets of non-HLA Abs, with little redundancy among individuals.CONCLUSIONS: Our findings indicate that preformed IgG Abs targeting non-HLA antigens expressed on glomerular endothelial cells are associated with early AMVR, and that in vitro cell-based assays are needed to improve risk assessments before transplant.
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- 2019
25. Immune checkpoint blockade for organ transplant patients with advanced cancer: how far can we go?
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Pauline De Bruyn, Véronique Del Marmol, Alain Le Moine, Piet Ost, Arnaud Devresse, Dirk Van Gestel, Sandrine Aspeslagh, Lieve Brochez, Vibeke Kruse, Hans Van Vlierberghe, Medical Oncology, Laboratory for Medical and Molecular Oncology, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, and UCL - (SLuc) Service de néphrologie
- Subjects
Graft Rejection ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Programmed Cell Death 1 Receptor ,MEDLINE ,Organ transplantation ,Liver Neoplasms/drug therapy ,03 medical and health sciences ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Antineoplastic Agents, Immunological/administration & dosage ,Internal medicine ,medicine ,Humans ,CTLA-4 Antigen ,Immunosuppressive Agents/administration & dosage ,business.industry ,Kidney Transplantation/methods ,Liver Neoplasms ,Programmed Cell Death 1 Receptor/antagonists & inhibitors ,Graft Rejection/immunology ,Sciences bio-médicales et agricoles ,Kidney Transplantation ,CTLA-4 Antigen/antagonists & inhibitors ,Advanced cancer ,Immune checkpoint ,Blockade ,Cancérologie ,030104 developmental biology ,surgical procedures, operative ,Allograft rejection ,030220 oncology & carcinogenesis ,business ,Immunosuppressive Agents - Abstract
Checkpoint inhibitors (CPIs) provide impressive response rates among immunocompetent patients with various solid tumors. So far, organ transplant recipients have been excluded from clinical studies due to the putative risk of allograft rejection however 48 cases of liver and renal transplant patients treated with CPI were already described in literature., SCOPUS: ar.j, info:eu-repo/semantics/published
- Published
- 2019
26. Host and microbial factors in kidney transplant recipients with Escherichia coli acute pyelonephritis or asymptomatic bacteriuria: a prospective study using whole-genome sequencing
- Author
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Brian Bd Johnston, Amélie Heinrichs, Louise Nienhaus, Frédérique Jacobs, Daniel Abramowicz, Maria Angeles Argudín, Alain Le Moine, James R. Johnson, Olivier Denis, Ricardo De Mendonça, Sandrine Roisin, Magali Dodémont, Judith Racapé, and Julien Coussement
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DNA, Bacterial ,Male ,Bacteriuria ,medicine.drug_class ,Urinary system ,Antibiotics ,030232 urology & nephrology ,Virulence ,030204 cardiovascular system & hematology ,urologic and male genital diseases ,virulome ,03 medical and health sciences ,0302 clinical medicine ,Immunity ,Escherichia coli ,Humans ,Medicine ,Prospective Studies ,Prospective cohort study ,Escherichia coli Infections ,Phylogeny ,ExPEC ,Transplantation ,Pyelonephritis ,business.industry ,Escherichia coli Proteins ,Sciences bio-médicales et agricoles ,Middle Aged ,medicine.disease ,Kidney Transplantation ,Transplant Recipients ,Anti-Bacterial Agents ,Vaccination ,Nephrology ,NGS ,Asymptomatic Diseases ,Immunology ,Female ,urinary tract infections ,Human medicine ,UPEC ,business ,Genome-Wide Association Study - Abstract
Urinary tract infection is the most common infection among kidney transplant recipients (KTRs). Many transplant physicians fear that host compromise will allow low-virulence strains to cause pyelonephritis in KTRs, so they often treat asymptomatic bacteriuria with antibiotics. Identification of the host/microbe factors that determine the clinical presentation (i.e. pyelonephritis versus asymptomatic bacteriuria) once an Escherichia coli strain enters a KTRs bladder could inform management decisions., info:eu-repo/semantics/published
- Published
- 2019
27. Chronic kidney disease as major determinant of the renal risk related to on-pump cardiac surgery: a single-center cohort study
- Author
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Perrine P Revercez, Bachar Ghassan El Oumeiri, Daniel De Backer, Aline Pourcelet, Jean-Michel Hougardy, Alain Le Moine, Frédéric Vanden Eynden, and Judith Racapé
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Male ,medicine.medical_specialty ,medicine.medical_treatment ,030232 urology & nephrology ,030204 cardiovascular system & hematology ,Kidney Function Tests ,urologic and male genital diseases ,Risk Assessment ,Cohort Studies ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,Predictive Value of Tests ,Internal medicine ,Preoperative Care ,medicine ,Humans ,Hospital Mortality ,Renal replacement therapy ,Cardiac Surgical Procedures ,Renal Insufficiency, Chronic ,Aged ,Retrospective Studies ,Cardiopulmonary Bypass ,urogenital system ,Vascular disease ,business.industry ,Incidence ,Acute kidney injury ,General Medicine ,Acute Kidney Injury ,Middle Aged ,medicine.disease ,female genital diseases and pregnancy complications ,Cardiac surgery ,Survival Rate ,Heart failure ,Cardiology ,Female ,Surgery ,Complication ,business ,Cohort study ,Kidney disease - Abstract
Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common complication and is associated with the poorest outcomes. Therefore, early prediction of CSA-AKI remains a major issue. Severity scores such as the STS score could estimate the risk of AKI preoperatively. The main objective of this study was to evaluate the risk factors of on-pump CSA-AKI and to assess the performance of the STS score in order to predict CSA-AKI.We identified 252 patients with on-pump cardiac surgery, and the STS score was defined retrospectively.AKI occurred in 14.6% (n = 37/252) of patients and renal replacement therapy was required in 21.6% of AKI (n = 8/37). CSA-AKI was associated with 35.1% in-hospital mortality (vs. 1.4%) and nearly doubled length of stay (14.5 vs. 8.0 d). The risk of CSA-AKI was mainly determined by preoperative morbidities such as chronic kidney disease, peripheral vascular disease, and severe congestive heart failure. Long cardio-pulmonary bypass time was also a determinant. CSA-AKI + patients exhibited higher STS renal risk (5.6% vs. 2.0%; p 0.0001), resulting in a good discrimination between AKI + and AKI - patients (area under curve [AUC] 0.80). Interestingly, a basal renal function ≤55 ml/min/1.73mOn-pump CSA-AKI was observed in nearly 15% of cases and was associated with poorer outcomes. Interestingly, the risk of CSA-AKI could be estimated preoperatively, thanks to the basal renal function, which exhibited an equal performance to the STS score.
- Published
- 2016
28. Therapeutic drug monitoring of enteric-coated mycophenolate sodium by limited sampling strategies is associated with a high rate of failure
- Author
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Karl Martin Wissing, Nilufer Broeders, Frédéric Cotton, Julien Coussement, Jean-Michel Hougardy, Daniel Abramowicz, Alain Le Moine, Dimitri Mikhalski, Laurette Maufort, Basic (bio-) Medical Sciences, and Clinical sciences
- Subjects
medicine.medical_specialty ,Urology ,kidney transplantation ,030230 surgery ,Mycophenolate ,030226 pharmacology & pharmacy ,Mycophenolic acid ,03 medical and health sciences ,Autres spécialisations médicales et paramédicales ,0302 clinical medicine ,Pharmacokinetics ,medicine ,enteric coating ,Kidney transplantation ,Transplantation ,medicine.diagnostic_test ,business.industry ,suppression of area under curves ,mycophenolate mofetil ,Area under the curve ,Mycophenolate Sodium ,medicine.disease ,Transplantation d'organes ,Surgery ,Nephrology ,Therapeutic drug monitoring ,Human medicine ,business ,pharmacokinetics ,medicine.drug - Abstract
Background Therapeutic drug monitoring of mycophenolic acid (MPA) is usually performed with a limited sampling strategy (LSS), which relies on a limited number of blood samples and subsequent extrapolation of the global exposure to MPA. LSS is usually performed successfully with mycophenolate mofetil (MMF), but data on enteric-coated mycophenolate sodium (EC-MPS) are scarce. Here, we evaluated the feasibility of 6-h LSS therapeutic drug monitoring with EC-MPS compared with MMF monitoring among kidney transplant recipients. Methods Sixty-two patients who received EC-MPS during the first 6 months of transplantation were compared with a matched group of 64 MMF-treated kidney transplant recipients. The area under the curve (AUC) was computed by LSS using multiple concentration time points (0, 1, 2, 3 and 6 h post-dose) and a trapezoidal rule. Patients had MPA therapeutic drug monitoring performed on two occasions, one within 2 weeks and the second after 3-4 months of transplantation. Results EC-MPS monitoring and MMF therapeutic drug monitoring were not interpretable in 34.5% (n = 40/116) and 1.8% (n = 2/112) of patients, respectively {relative risk [RR] 19.3 [95% confidence interval (CI) 4.8-78.0]; P < 0.0001}. The main cause of abnormal EC-MPS therapeutic drug monitoring was delayed absorption of both the previous evening and the morning dose, resulting in MPA plasma levels before the next morning dose being higher than MPA plasma levels measured at 1, 2 and 3 h after taking EC-MPS. Cyclosporin in association with MMF significantly increased the risk of low AUC values (30% during the first 6 months of renal transplantation. Delayed pharmacokinetics was the main reason. In contrast, the risk of therapeutic drug monitoring failure was substantially lower with MMF., SCOPUS: ar.j, info:eu-repo/semantics/published
- Published
- 2016
29. MP61-07 MYELOID HO-1 PREVENTS KIDNEY REMOTE ORGAN DAMAGE FOLLOWING RENAL ISCHEMIA-REPERFUSION INJURY
- Author
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Jean-Michel Hougardy, Thierry Roumeguere, Oberdan Leo, Eric Wespes, Véronique Flamand, Maxime Rossi, Sandrine Delbauve, and Alain Le Moine
- Subjects
Pathology ,medicine.medical_specialty ,Kidney ,Myeloid ,medicine.anatomical_structure ,business.industry ,Urology ,medicine ,Remote organ ,business ,Renal ischemia reperfusion - Published
- 2018
30. Mouse Models of Experimental Vascularized Composite Allotransplantation
- Author
-
Alain Le Moine and Zhanzhuo Li
- Subjects
Transplantation ,Mixed chimerism ,Hepatology ,business.industry ,medicine.medical_treatment ,Immunology ,Immunosuppression ,Revascularization ,Bioinformatics ,Vascularized Composite Allotransplantation ,Clinical Practice ,stomatognathic diseases ,Tolerance induction ,Transplant surgery ,Nephrology ,otorhinolaryngologic diseases ,medicine ,Surgery ,business - Abstract
The clinical practice of vascularized composite allotransplantation (VCA) has been limited by the potential side effects of chronic immunosuppression. Studies using rodent models have been useful for dissecting mechanisms underlying immunological events induced by VCA and for developing protocols such as mixed chimerism for tolerance induction. Mouse models of VCA have great advantages over rat and other rodents with regard to dissection of immunologic mechanisms; however, the microsurgical revascularization procedures that are required are much more difficult. Here we review recent advances in surgical and immunological methods for successful VCA in the mouse model.
- Published
- 2014
31. T-bet or IFNγ Neutralization for Blocking Islet Allograft Rejection?
- Author
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Alain Le Moine
- Subjects
Transplantation ,geography ,geography.geographical_feature_category ,Chemistry ,Blocking (radio) ,Islets of Langerhans Transplantation ,Allografts ,Islet ,Neutralization ,Islets of Langerhans ,03 medical and health sciences ,0302 clinical medicine ,Allograft rejection ,Immunology ,030212 general & internal medicine ,030215 immunology - Published
- 2018
32. Preemptive reduction of immunosuppression upon high urinary polyomavirus loads improves patient survival without affecting kidney graft function
- Author
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Anwar Hamade, Alain Le Moine, Pierre Vereerstraeten, Jean-Michel Hougardy, Fadoua El Mountahi, Emine Nilufer Broeders, and Judith Racapé
- Subjects
Graft Rejection ,Male ,medicine.medical_specialty ,Urinary system ,medicine.medical_treatment ,JC virus ,Urology ,030230 surgery ,medicine.disease_cause ,Single Center ,Nephropathy ,03 medical and health sciences ,0302 clinical medicine ,HLA Antigens ,Risk Factors ,Medicine ,Humans ,Viremia ,Kidney transplantation ,Retrospective Studies ,Immunosuppression Therapy ,Transplantation ,Polyomavirus Infections ,business.industry ,Graft Survival ,Panel reactive antibody ,Immunosuppression ,Middle Aged ,Viral Load ,medicine.disease ,JC Virus ,Kidney Transplantation ,Transplant Recipients ,BK virus ,Tumor Virus Infections ,Infectious Diseases ,Treatment Outcome ,BK Virus ,Immunology ,030211 gastroenterology & hepatology ,Female ,Kidney Diseases ,business ,Immunosuppressive Agents - Abstract
Polyomavirus (PV) is a major cause of kidney graft disease. Monitoring by polymerase chain reaction (PCR) on blood is currently recommended. In order to avoid irreversible lesions, we investigated the clinical impact of preemptive reduction of immunosuppression (IS) in kidney transplant recipients (KTR) upon detection of high urinary PV (Upv) load, including BK virus and JC virus.From 2000 to 2011, in our single center, 789 consecutive KTR were distributed into 4 groups, according to the maximal Upv levels (by PCR) during the first year and the therapeutic option: (A) Upv10The preemptive reduction of IS (group Ca) increased patient survival as compared with all other groups (P.05), did not modify graft function, and increased graft survival vs group A (risk ratio: 5.7, confidence interval: 1.8-18.1, P=.003). Differences for risk factors are as follows (groups Ca vs A): incidence of human leukocyte antigen (HLA) immunization (5% panel reactive antibodies): 3% vs 8% (P=.05), number of HLA mismatches: 2.7 vs 2.5 (P=.049), and incidence of acute rejection: 9.8% vs 24.2% (P=.005). PV-associated nephropathy occurred only in group Ca (2% of total grafts) without effect on patient or graft outcome.The reduction of IS in patients with high Upv loads is beneficial for patient survival and does not affect graft survival or graft function.
- Published
- 2015
33. Combined introduction of anti-IL2 receptor antibodies, mycophenolic acid and tacrolimus: effect on malignancies after renal transplantation in a single-centre retrospective cohort study
- Author
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Véronique Del Marmol, Nilufer Broeders, Philippe Madhoun, Daniel Abramowicz, Philippe Braconnier, Annick Massart, Alain Le Moine, Karl Martin Wissing, Lidia Ghisdal, Judith Racapé, Mireille N Kianda, and Anne Lemy
- Subjects
Adult ,Graft Rejection ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Azathioprine ,Gastroenterology ,Tacrolimus ,Mycophenolic acid ,Neoplasms ,Internal medicine ,Humans ,Medicine ,Kidney transplantation ,Retrospective Studies ,Transplantation ,Antibiotics, Antineoplastic ,business.industry ,Graft Survival ,Cancer ,Receptors, Interleukin-2 ,Immunosuppression ,Middle Aged ,Mycophenolic Acid ,Prognosis ,medicine.disease ,Kidney Transplantation ,Antibodies, Anti-Idiotypic ,Survival Rate ,Drug Combinations ,Nephrology ,Immunology ,Kidney Failure, Chronic ,Female ,Skin cancer ,business ,Immunosuppressive Agents ,Follow-Up Studies ,medicine.drug - Abstract
Background. Several studies suggest that the introduction of tacrolimus (TRL), mycophenolic acid (MPA) and interleukin 2 receptor antibodies (IL2Ra) as single drugs more than a decade ago has not increased the risk of malignancy after renal transplantation. However, only limited data are available on their carcinogenic effects when used in combination as a potent immunosuppressive regimen. Methods. A retrospective single-centre cohort study on 929 adult renal transplant recipients. Investigation of the effect of two consecutive immunosuppressive regimens [1993–98, N ¼ 405, anti-lymphocyte antibodies, cyclosporine and azathioprine (AZA); 1999–2007, N ¼ 524, predominantly IL2Ra, TRL and MPA] on the incidence rate of skin cancer, solid tumours and post-transplant lymphoproliferative disease (PTLD). Results. In total, 365 malignancies developed among 113 patients. As compared to the previous cyclosporine and AZA-based immunosuppression, the introduction of the new immunosuppressive regimen did not increase the incidence rate of skin cancer [rate ratio 0.84; 95% confidence interval (CI) 0.48–1.46], solid tumours (0.89; 95% CI 0.46–1.67) and PTLD (0.82; 95% CI 0.28–2.21). Patients treated with the more recent regimens less frequently developed multiple skin cancers and invasive squamous cell cancer. Skin cancer after transplantation was strongly associated with the development of solid tumours (odds ratio 5.2; P < 0.0001). The introduction of the new immunosuppressive drugs reduced the incidence of first year acute rejection from 34.8 to 13.2% (P < 0.0001). Conclusion. Although significantly more efficient in the prevention of acute rejection, the introduction of TRL, MPA and IL2Ra-based immunosuppression after kidney transplantation was not associated with an increased incidence of skin cancer, solid tumours or PTLD.
- Published
- 2011
34. Partial depletion of CD4+CD25+Foxp3+ T regulatory cells significantly increases morbidity during acute phase Toxoplasma gondii infection in resistant BALB/c mice
- Author
-
Stéphane De Craeye, Sushila D'Souza, Sophie Detienne, Vijay Morampudi, Michel Y Braun, and Alain Le Moine
- Subjects
Ratón ,medicine.medical_treatment ,Immunology ,chemical and pharmacologic phenomena ,Biology ,T-Lymphocytes, Regulatory ,Microbiology ,Lymphocyte Depletion ,Proinflammatory cytokine ,BALB/c ,Mice ,Antigens, CD ,Ileum ,medicine ,Animals ,IL-2 receptor ,Cells, Cultured ,Mice, Inbred BALB C ,Lamina propria ,Antibodies, Monoclonal ,FOXP3 ,Toxoplasma gondii ,hemic and immune systems ,Sciences bio-médicales et agricoles ,biology.organism_classification ,Mice, Inbred C57BL ,Infectious Diseases ,Cytokine ,medicine.anatomical_structure ,Acute Disease ,Disease Progression ,Cytokines ,Female ,Toxoplasma ,Toxoplasmosis - Abstract
CD4+CD25+Foxp3+ T regulatory (Treg) cells, are known to regulate responses to infectious agents. Here we compared disease progression in BALB/c and C57BL/6(B6) mice infected perorally with Toxoplasma gondii for 7 days and examined the affect of partial depletion of Treg cells in these mice. BALB/c mice were seen to be resistant to peroral infection whereas B6 mice were susceptible in terms of mortality. Although the depletion of Treg cells before infection had no effect on the survival of B6 or BALB/c mice, it resulted in increased parasite burdens in BALB/c mice, especially in the lamina propria, but not in B6 mice. Pro-inflammatory cytokines were also increased in Treg cells depleted BALB/c mice as compared to B6 mice. In addition Treg cell depleted BALB/c mice displayed increased ileal histopathology compared to their non-treated counterparts. These findings provide evidence for the contribution of Treg cells, in the resistance of BALB/c mice against peroral T. gondii infection.
- Published
- 2011
35. Interleukin 17–producing T helper cells in alloimmunity
- Author
-
B. Vokaer, Alain Le Moine, Louis-Marie Charbonnier, Virginie De Wilde, and Fleur Samantha Benghiat
- Subjects
Neutrophils ,CD8-Positive T-Lymphocytes ,Biology ,T-Lymphocytes, Regulatory ,Mice ,Interleukin 21 ,Th2 Cells ,Transplantation Immunology ,Interleukin 25 ,Animals ,Humans ,Transplantation, Homologous ,Cytotoxic T cell ,IL-2 receptor ,Interleukin 3 ,Transplantation ,Interleukin-17 ,Toll-Like Receptors ,Immunologic Deficiency Syndromes ,T-Lymphocytes, Helper-Inducer ,Th1 Cells ,Interleukin 33 ,Interleukin 10 ,Treatment Outcome ,Immunology ,Interleukin 12 ,Cytokines - Abstract
Interleukin (IL) 17 is a proinflammatory cytokine already known to play a defense role against microbes and a pathogenic role in a number of autoimmune diseases. Although IL-17 can be produced by a variety of cells including neutrophils, CD8+, NK, and gamma-delta T cells, the concept of IL-17-secreting CD4+ T helper cells (Th17), distinct from Th1 and Th2, recently emerged. Herein, we discuss arguments in favor of a Th17-mediated alternative pathway of allograft rejection based on clinical and experimental observations drawn from the literature. We also discuss the complex interplays among regulatory T cells and Th17 cells in the allogeneic context.
- Published
- 2009
36. Donor T-Cell Development in Host Thymus After Heterotopic Limb Transplantation in Mice
- Author
-
Frederic Schuind, Michel Goldman, Carole Kubjak, Fleur Samantha Benghiat, Zhanzhuo Li, and Alain Le Moine
- Subjects
Graft Rejection ,Male ,Transplantation, Heterotopic ,T-Lymphocytes ,T cell ,medicine.medical_treatment ,Mice, Transgenic ,Spleen ,Thymus Gland ,Transplantation Chimera ,Biology ,urologic and male genital diseases ,Mice ,medicine ,Animals ,Bone Marrow Transplantation ,Cell Proliferation ,Homeodomain Proteins ,Transplantation ,Limb transplantation ,Extremities ,T lymphocyte ,Mice, Inbred C57BL ,Thymectomy ,medicine.anatomical_structure ,Immunology ,Thy-1 Antigens ,Immunocompetence - Abstract
We developed a mouse model of heterotopic limb transplantation in which we took advantage of Thy1.1 and Thy1.2 congenic strains to track and characterize donor T cells, to determine the role of recipient's thymus in mixed T-cell chimerism induction as well as transplant immunocompetence. The vascularized Thy1.1 limb graft composed of femur, muscle, and skin (VBT) survived long-term in more than 87.5% of Thy1.2 recipients. Percentages of donor-type Thy1.1 T cells increased from day 30 to 90 in thymus and spleen of recipients. Most peripheral donor T cells displayed a naïve phenotype and a few others were regulatory T cells. Thymectomy prevented peripheral T-cell chimerism. Congenic VBT in immunodeficient RAG mice restored their ability to reject skin allografts. These observations suggest that donor T cells differentiated in host thymus might contribute to maintenance of mixed chimerism after transplantation of tissue composite grafts that include vascularized bone.
- Published
- 2007
37. The DESCARTES-Nantes survey of kidney transplant recipients displaying clinical operational tolerance identifies 35 new tolerant patients and 34 almost tolerant patients
- Author
-
Michaela Prokopova, Friedrich Thaiss, Andries J. Hoitsma, Bruno Hurault de Ligny, Anja Mühlfeld, Séverine Martin, Oliver Gross, Władysław Sułowicz, Annick Massart, Judith Racapé, Miguel Angel Gentil Govantes, A. Yussim, Frieder Keller, Umberto Maggiore, Matthew Howse, Gian Benedetto Piredda, Ricardo Lauzurica, Magali Giral, Luis Antonio Jiménez del Cerro, Marie-Christine Moal, Tomas Reischig, François Glowacki, Jean-François Subra, Bénédicte Janbon, Consuelo De Biase, María José Pérez-Sáez, Marian Klinger, Goce Spasovski, Philippe Gatault, Gaetano La Manna, David Berglund, Cem Tugmen, Giovanni M. Frascà, Uyen Huynh-Do, Christophe Legendre, Annaïck Pallier, Christopher Dudley, Mélanie Chesneau, Laura Braun, Daniel Abramowicz, Karine Hadaya, Christian Noel, Evangeline Pillebout, Carmen Díaz-Corte, Julio Pascual, Ondrej Viklicky, Florence Villemain, Luigi Biancone, Ana Ramírez Puga, Marije C. Baas, Alain Le Moine, Marc Abramowicz, Frederike J. Bemelman, Rainer Oberbauer, Jean-Paul Soulillou, Nurhan Seyahi, Jadranka Buturović Ponikvar, Johan W. de Fijter, Maarten Naesens, Vania Cuna, Klemens Budde, Serhan Tuglular, Pierrick Guerif, Angel Alonso Hernandez, Piero Stratta, Arnaud Garnier, Hulya Colak, K. Clemente, Sophie Brouard, Marc Hazzan, Søren Schwartz Sørensen, Giuseppe Orlando, Daniel Serón, Luboslav Beňa, Quirino Lai, Francesco Pisani, Aisling E. Courtney, Alexandre Dufay, Mehmet Sukru Sever, Thomas Wekerle, Hervé Le Monies De Sagazan, Hakim Mazouz, Aljoša Kandus, Maria Carmen Cantarell, André Gaasbeek, Massart, A, Pallier, A, Pascual, J, Viklicky, O, Budde, K, Spasovski, G, Klinger ,M, Sever, MS, Sørensen, SS, Hadaya, K, Oberbauer, R, Dudley, C, De Fijter, JW, Yussim, A, Hazzan, M, Wekerle, T, Berglund, D, De Biase, C, Pérez-Sáez, MJ, Mühlfeld, A, Orlando, G, Clemente, K, Lai, Q, Pisani, F, Kandus, A, Baas, M, Bemelman, F, Ponikvar, JB, Mazouz ,H, Stratta, P, Subra, JF, Villemain, F, Hoitsma, A, Braun, L, Cantarell, MC, Colak, H, Courtney, A, Frasca, GM, Howse, M, Naesens, M, Reischig, T, Serón, D, Seyahi, N, Tugmen, C, Alonso Hernandez, A, Beňa, L, Biancone, L, Cuna, V, Díaz-Corte, C, Dufay, A, Gaasbeek, A, Garnier, A, Gatault, P, Gentil Govantes, MA, Glowacki, F, Gross, O, Hurault de Ligny, B, Huynh-Do, U, Janbon, B, Jiménez Del Cerro, LA, Keller, F, La Manna, Gaetano, Lauzurica, R, Le Monies De Sagazan, H, Thaiss, F, Legendre, C, Martin, S, Moal, MC, Noël, C, Pillebout, E, Piredda, GB, Puga, AR, Sulowicz, W, Tuglular, S, Prokopova, M, Chesneau, M, Le Moine, A, Guérif, P, Soulillou, JP, Abramowicz, M, Giral, M, Racapé, J, Maggiore, U, Brouard, S, Abramowicz, D, AII - Amsterdam institute for Infection and Immunity, Nephrology, Renal Unit [Brussels, Belgium] (ULB), Université libre de Bruxelles (ULB)-CUB Hôpital Erasme [Bruxelles, Belgium], Medical Genetics Department [Brussels, Belgium], Université libre de Bruxelles (ULB), 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), Nephrology [Barcelona, Spain] (Hospital del Mar), Hospital del Mar [Barcelona, Spain], Department of Nephrology [Prague, Czech Republic] (Transplant Center), Institute for Clinical and Experimental Medicine (IKEM), Department of Nephrology [Berlin, Germany], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Nephrology [Skopje, Macedonia], Ss. Cyril and Methodius University in Skopje, Nephrology and Transplantation Medicine [Wrocław, Poland], University of Wrocław [Poland] (UWr), Internal Medicine, Nephrology [Istanbul, Turkey], Istanbul School of Medicine [Istanbul, Turkey], Nephrology P [Copenhagen, Denmark], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Nephrology and Transplantation [Geneva, Switzerland], Geneva University Hospitals - HUG [Switzerland], Department of Medicine III–Nephrology, Hypertension and Renal Transplantation [Linz, Austria], Krankenhaus Elisabethinen Linz [Linz, Austria], Richard Bright Renal Centre [Bristol, UK], Southmead Hospital [Bristol, UK]-North Bristol NHS Trust [Bristol, UK], Department of Nephrology [Leiden, The Netherlands], Leiden University Medical Center (LUMC), Department of Transplantation [Tel Aviv, Israël] (Rabin Medical Center), Rabin Medical Center [Tel Aviv, Israël]-Tel Aviv University Sackler School of Medicine [Tel Aviv, Israël], Département de Néphrologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of Surgery [Vienna, Austria] (Section of Transplantation Immunology), Medizinische Universität Wien = Medical University of Vienna, Section of Clinical Immunology [Uppsala, Sweden] (Department of Immunology, Genetics and Pathology), Uppsala University, UOS Trapianti Rene Pancreas [Parma, Italy] (Centro Trapianti di Parma), Azienda Ospedaliero-Universitaria di Parma, Department of Nephrology [Aachen, Germany], University Hospital Aachen, Section of Transplantation [Winston-Salem, NC, USA] (Department of Surgery), Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center-Wake Forest Baptist Medical Center, U.O.C. Trapianti D’Organo [L’Aquila, Italy], Department of Nephrology [Ljubljana, Slovenia] (Renal Transplantation Centre Ljubljana), University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), Kidney Diseases [Nijmegen, The Netherlands], Radboudumc Nijmegen [The Netherlands], Renal Transplant Unit [Amsterdam, The Netherlands] (Department of Nephrology), Academic Medical Center [Amsterdam, Netherlands], Unité de Transplantation Rénale et Pancréatique [CHU Sud, Amiens] (Service de Néphrologie), CHU Amiens-Picardie, Department of Translational Medicine [Novara, Italy], Amedeo Avogadro University of Eastern Piedmont, Service de Néphrologie-Dialyse-Transplantation [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), service de Néphrologie et Transplantation Rénale [CHU Strasbourg] (Hôpital de jour de Néphrologie), Centre Hospitalier Universitaire de Strasbourg (CHU de Strasbourg )-Nouvel Hôpital Civil - NHC [Strasbourg], Pediatric Nephrology [Barcelona, Spain] (Vall d’Hebron Hospital), Universitat Autònoma de Barcelona (UAB)-Vall d'Hebron University Hospital [Barcelona], Department of Nephrology [Izmir, Turkey], Tepecik Training and Research Hospital [Izmir, Turkey], Regional Nephrology Unit [Belfast, UK], Belfast City Hospital [Belfast, UK], Nefrologia, Dialisi e Trapianto di rene [Ancona, Italy], AO Torrette Umberto I [Ancona, Italy], Nephrology/Transplantation [Liverpool, UK], Royal Liverpool University Hospital [Liverpool, UK], Department of Nephrology and Renal Transplantation [Leuven, Belgium], University Hospitals Leuven [Leuven]-Catholic University Leuven, Nephrology Ward [Pilsen, Czech Republic] (Department of Internal Medicine), University Hospital Pilsen [Pilsen, Czech Republic], Istanbul University, Servicio de Nefrología, Hospital Universitario, A Coruña, Transplant Centre, University Hospital Louis Pasteur Kosice, University of Turin, St. Orsola University Hospital, University of Bologna, Hospital Universitario Central de Asturias (HUCA), Service Néphrologie [Roubaix], Hôpital Victor Provo, Leids Universitair Medisch Centrum [Leiden, The Netherlands], Néphrologie - Médecine Interne - Hypertension Pédiatrique, Hôpital des Enfants, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service Néphrologie - Immunoclinique [CHRU Tours], Hôpital Bretonneau, Hospital Universitario Virgen del Rocío [Sevilla], Service de Néphrologie et Transplantation rénale [CHRU-lille], University Medicine Göttingen, 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), University of Bern [Bern, Switzerland] (University Hospital Bern ), Transplantation rénale [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Hospital General Universitario de Alicante, Universitätsklinikum Ulm - University Hospital of Ulm, Hospital Universitario Germans Trias I Pujol, University Hospital Hamburg-Eppendorf, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hémodialyse et de Néphrologie [Libourne], Hôpital Robert Boulin, CHRU - Service de néphrologie, dialyse et transplantation rénale, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Département de Néphrologie et transplantation [Hôpital Saint Louis - APHP], 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), Kidney Transplant Az. Osp. G. Brotzu, Hospital Universitario Insular de Gran Canaria, University Hospital in Krakow, Marmara School of Medicine Hastanesi, Institute of Transplantation Urology and Nephrology [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire, Research Center of Epidemiology, Biostatistics and Clinical Research, Nephrology-Renal Transplantation Department, Université libre de Bruxelles (ULB)-Universitair Ziekenhuis Antwerp, ERA-EDTA-DESCARTES working group, the Fonds Erasme (research grant), the Fonds Carine Vyghen, the Fonds Horlait-Dapsens, the RTRS Fondation de Coopération Scientifique CENTAURE and the IHUCesti project., ANR-10-IBHU-0005,CESTI (TSI-IHU),Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU)(2010), 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, Ss. Cyril and Methodius University in Skopje (UKIM), Tel Aviv University (TAU)-Rabin Medical Center [Tel Aviv, Israël], Università degli studi di Torino = University of Turin (UNITO), University of Bologna/Università di Bologna, Service Néphrologie, médecine interne et hypertension pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CUB Hôpital Erasme [Bruxelles, Belgium]-Université libre de Bruxelles (ULB), and Hadaya, Karine
- Subjects
0301 basic medicine ,Nephrology ,Graft Rejection ,Male ,medicine.medical_treatment ,030230 surgery ,Kidney transplant ,0302 clinical medicine ,Surveys and Questionnaires ,Allograft survival ,Kidney transplantation ,ddc:616 ,Graft Survival/immunology ,Survival Rate/trends ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Incidence ,Graft Survival ,Immunosuppression ,operational tolerance ,Transplantation ,3. Good health ,Europe ,Survival Rate ,frequency ,minimally immunosuppressed patients ,Female ,Hemodialysis ,Graft Rejection/epidemiology/immunology/prevention & control ,Homologous ,Adult ,medicine.medical_specialty ,Ronyons -- Trasplantació -- Aspectes immunològics ,Immunosuppression/methods ,kidney transplantation ,Europe/epidemiology ,03 medical and health sciences ,Immune Tolerance/immunology ,Internal medicine ,medicine ,Immune Tolerance ,Humans ,Transplantation, Homologous ,Survival rate ,Immunosuppression Therapy ,graft survival ,business.industry ,medicine.disease ,Kidney Transplantation ,Transplant Recipients ,Surgery ,030104 developmental biology ,Operational tolerance ,Human medicine ,Renal disorders Radboud Institute for Health Sciences [Radboudumc 11] ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Background Kidney recipients maintaining a prolonged allograft survival in the absence of immunosuppressive drugs and without evidence of rejection are supposed to be exceptional. The ERA-EDTA-DESCARTES working group together with Nantes University launched a European-wide survey to identify new patients, describe them and estimate their frequency for the first time. Methods Seventeen coordinators distributed a questionnaire in 256 transplant centres and 28 countries in order to report as many operationally tolerant patients (TOL; defined as having a serum creatinine
- Published
- 2015
38. Delayed Graft Function in Kidney Transplants: Time Evolution, Role of Acute Rejection, Risk Factors, and Impact on Patient and Graft Outcome
- Author
-
Pierre Vereerstraeten, Jean-Michel Hougardy, Martin Chaumont, Thomas Baudoux, Judith Racapé, Daniel Abramowicz, Anwar Hamade, Annick Massart, Nilufer Broeders, Dimitri Mikhalsky, Alain Le Moine, and Fadoua El Mountahi
- Subjects
medicine.medical_specialty ,Kidney ,Néphrologie - urologie ,Article Subject ,Receiver operating characteristic ,business.industry ,Incidence (epidemiology) ,Area under the curve ,lcsh:Surgery ,Diuresis ,Perioperative ,lcsh:RD1-811 ,Logistic regression ,Transplantation d'organes ,Sciences biomédicales ,Delayed Graft Function ,Surgery ,medicine.anatomical_structure ,Internal medicine ,Cardiology ,Medicine ,Human medicine ,business ,Research Article - Abstract
Background. Although numerous risk factors for delayed graft function (DGF) have been identified, the role of ischemia-reperfusion injury and acute rejection episodes (ARE) occurring during the DGF period is ill-defined and DGF impact on patient and graft outcome remains controversial. Methods. From 1983 to 2014, 1784 kidney-only transplantations from deceased donors were studied. Classical risk factors for DGF along with two novel ones, recipient's perioperative saline loading and residual diuresis, were analyzed by logistic regression and receiver operating characteristic (ROC) curves. Results. Along with other risk factors, absence of perioperative saline loading increases acute rejection incidence (OR = 1.9 [1.2-2.9]). Moreover, we observed two novel risk factors for DGF: patient's residual diuresis ≤500 mL/d (OR = 2.3 [1.6-3.5]) and absence of perioperative saline loading (OR = 3.3 [2.0-5.4]). Area under the curve of the ROC curve (0.77 [0.74-0.81]) shows an excellent discriminant power of our model, irrespective of rejection. DGF does not influence patient survival (P = 0.54). However, graft survival is decreased only when rejection was associated with DGF (P < 0.001). Conclusions. Perioperative saline loading efficiently prevents ischemia-reperfusion injury, which is the predominant factor inducing DGF. DGF per se has no influence on patient and graft outcome. Its incidence is currently close to 5% in our centre., info:eu-repo/semantics/published
- Published
- 2015
39. Regulatory Role of Host CD8+ T Lymphocytes in Experimental Graft-versus-Host Disease across a Single Major Histocompatibility Complex Class II Incompatibility
- Author
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Frédéric Paulart, Claude Habran, Michel Goldman, Najate Ouled Haddou, Alain Le Moine, Véronique Flamand, Aurore de Lavareille, Isabelle Salmon, Nathalie Nagy, and Cynthia Prigogine
- Subjects
CD4-Positive T-Lymphocytes ,T cell ,Graft vs Host Disease ,CD8-Positive T-Lymphocytes ,Major histocompatibility complex ,Mice ,Interleukin 21 ,Th2 Cells ,Isoantibodies ,Eosinophilia ,medicine ,Animals ,Cytotoxic T cell ,IL-2 receptor ,Antigen-presenting cell ,Cell Proliferation ,Mice, Knockout ,Transplantation ,Interleukin-13 ,biology ,Histocompatibility Antigens Class II ,Immunoglobulin E ,Natural killer T cell ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Blood Group Incompatibility ,Immunology ,biology.protein ,Interleukin-5 ,beta 2-Microglobulin ,CD8 - Abstract
Background. CD8 + T cells are known to regulate type 2 helper T cell (Th2) alloreactive immune responses but their mode of activation is unclear. We investigated the role ofhost CD8 + T cells in experimental Th2-type graft-versus-host disease (GVHD) where donor/recipient disparity is restricted to a single major histocompatibility complex (MHC) class II antigen. Methods. Immunoglobulin (Ig) E serum levels, eosinophilia and lymphoid tissue hyperplasia were compared after injection of bm12 CD4 + T cells in either wild-type or CD8 + T cell-deficient (CD8 -/- ) C57BL/6 mice. In vitro, we explored effects of the addition of CD8 + T cells from wild-type or IFN-γ -/- mice in mixed leukocyte cultures prepared with β2 microglobulin-deficient (β2m -/- ) CD4 + T cells as responders or β2m -/- dendritic cells as stimulators. Results. HyperIgE resolved after 3 weeks in wild-type hosts whereas it persisted for 6 weeks in CD8 -/- hosts. Eosinophil infiltrates in lymph nodes were significantly enhanced in CD8 -/- hosts. Increased serum levels of IL-5 and IL-13 in CD8 -/- hosts confirmed the enhancement ofTh2-type responses in the context of recipient CD8 + T cell deficiency. Hyperplasia of lymph nodes and spleen were similar in both groups, as well as in vivo proliferation of donor CD4 + T cells. In vitro, CD8 + T cell regulation of the alloreactive Th2 response depended on their production of IFN- and did not require expression of β2m on CD4 + T cells or antigen-presenting cells. Conclusions. Host CD8 + T cells regulate alloreactive Th2 responses during graft-versus-host disease through an IFN-γ dependent pathway, independently of the recognition of β2m-associated MHC class I molecules.
- Published
- 2005
40. A Rapid Test to Monitor Alloreactive Responses in Whole Blood Using Real-Time Polymerase Chain Reaction
- Author
-
Michel Goldman, Alain Le Moine, Marc Andrien, Bernard de Hemptinne, Etienne Dupont, Roberto Troisi, Patrick Stordeur, Michel Toungouz, Ling Zhou, and Vincent Donckier
- Subjects
Time Factors ,CD3 Complex ,T-Lymphocytes ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Peripheral blood mononuclear cell ,Interferon-gamma ,Humans ,Transplantation, Homologous ,Medicine ,RNA, Messenger ,Whole blood ,Transplantation Chimera ,Transplantation ,Reverse Transcriptase Polymerase Chain Reaction ,business.industry ,Histocompatibility Testing ,HLA-DR Antigens ,Flow Cytometry ,Hematopoietic Stem Cells ,Liver Transplantation ,Haematopoiesis ,Tolerance induction ,Real-time polymerase chain reaction ,Antibody Formation ,Immunology ,Immunologic Techniques ,Leukocytes, Mononuclear ,Cytokines ,Interleukin-2 ,Transplantation Tolerance ,Lymphocyte Culture Test, Mixed ,Stem cell ,Peptides ,business - Abstract
Rapid, simple, and reliable assays to monitor allogeneic responses are essential for the safe development of novel protocols of tailored immunosuppression. Herein, we describe a real-time polymerase chain reaction method based on interleukin-2 and interferon-gamma mRNA quantification upon stimulation of whole blood with allogeneic T cell-depleted peripheral blood mononuclear cells. The technique requires only small blood volumes and results can be obtained within 48 hours. Data obtained in a liver transplant patient receiving a tolerance induction protocol based on the infusion of donor-type hematopoietic stem cells suggest that this rapid whole blood mixed lymphocyte reaction assay could be valuable for the monitoring of patients undergoing solid organ or hematopoietic stem cell transplantation.
- Published
- 2005
41. Le rôle des neutrophiles dans le rejet d'allogreffe
- Author
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Michel Goldman, Daniel Abramowicz, Alain Le Moine, Sofia Buonocore, Véronique Flamand, and Murielle Surquin
- Subjects
Innate immune system ,business.industry ,Lymphocyte ,Chemotaxis ,Granulocyte ,Histocompatibility ,Transplantation ,surgical procedures, operative ,medicine.anatomical_structure ,Immune system ,Nephrology ,Immunology ,Medicine ,business ,Interleukin 4 - Abstract
Because rejection of allografts is primarily caused by T and B lymphocyte responses to allogeneic histocompatibility molecules, the role of innate immunity in organ transplant rejection is often overlooked. However, the very first damages to vascularized organ allografts are caused by ischemia-reperfusion, an inflammatory reaction involving activation of vascular endothelial cells and release of neutrophil chemoattractants. Herein, we review experimental observations suggesting that the early neutrophil influx in organ transplants favors T cell-mediated rejection.
- Published
- 2005
42. Dominant tolerance: activation thresholds for peripheral generation of regulatory T cells
- Author
-
Herman Waldmann, Duncan Howie, Alain Le Moine, Tse-Ching Chen, Stephen P. Cobbold, and Luis Graca
- Subjects
business.industry ,T-Lymphocytes ,Immunology ,Lymphocyte Activation ,medicine.disease_cause ,Treg cell ,Peripheral ,Autoimmunity ,Immune tolerance ,Transplantation ,Phenotype ,Antigenic stimulation ,Immune Tolerance ,medicine ,Animals ,Immunology and Allergy ,Transplantation Tolerance ,business ,Transforming growth factor - Abstract
In recent years, regulatory T (Treg) cells have reached centre-stage in immune tolerance research. A role for Treg cells in preventing autoimmunity or generating transplantation tolerance is now undisputed. However, in spite of a surge in publications dedicated to Treg cells, surprisingly little is known about their induction, biology and mechanisms of action. In this Opinion, we discuss the facts and the controversies regarding their role in transplantation tolerance. We suggest that peripheral generation of Treg cells, crucial for the generation of dominant transplantation tolerance, might be a consequence of sustained suboptimal antigenic stimulation, and that transforming growth factor-β (TGF-β) might contribute to this process by increasing the threshold for T-cell activation. © 2004 Elsevier Ltd. All rights reserved.
- Published
- 2005
43. Dominant transplantation tolerance
- Author
-
Alain Le Moine, Luis Graca, Stephen P. Cobbold, and Herman Waldmann
- Subjects
CD40 ,medicine.medical_treatment ,Immunology ,Immunosuppression ,Biology ,Transplantation ,Lymphatic system ,Mechanism of action ,medicine ,biology.protein ,Immunology and Allergy ,IL-2 receptor ,medicine.symptom ,Antibody ,CD154 - Abstract
Long-term allograft survival in the absence of continuous immunosuppression can be induced following a short treatment of nondepleting antibodies, such as those that target CD4 or CD154 (CD40 ligand). It is now established that this may involve dominant tolerance mechanisms that are maintained by CD4+ regulatory T cells present within the lymphoid tissue and the tolerated graft. The phenotype of these cells, their relationship to CD4+CD25+ T cells, and the mechanism of action are still controversial.
- Published
- 2003
44. CD4+CD25+ and CD4+CD25− T Cells Act Respectively as Inducer and Effector T Suppressor Cells in Superantigen-Induced Tolerance
- Author
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Claude Habran, Michel Goldman, Alain Le Moine, Michel Y Braun, Pascal Feunou, and Lionel F. Poulin
- Subjects
CD4-Positive T-Lymphocytes ,Staphylococcus aureus ,T cell ,Immunology ,Dose-Response Relationship, Immunologic ,Down-Regulation ,Epitopes, T-Lymphocyte ,chemical and pharmacologic phenomena ,Cell Separation ,Thymus Gland ,Biology ,T-Lymphocytes, Regulatory ,Drug Administration Schedule ,Lymphocyte Depletion ,Enterotoxins ,Mice ,Interleukin 21 ,Antigens, CD ,Cell Movement ,T-Lymphocyte Subsets ,medicine ,Animals ,Immunology and Allergy ,Cytotoxic T cell ,CTLA-4 Antigen ,IL-2 receptor ,Antigen-presenting cell ,Interleukin 3 ,Clonal Anergy ,Mice, Inbred BALB C ,Superantigens ,FOXP3 ,Receptors, Interleukin-2 ,hemic and immune systems ,Natural killer T cell ,Antigens, Differentiation ,Molecular biology ,biological factors ,medicine.anatomical_structure ,Female ,Injections, Intraperitoneal ,Spleen - Abstract
The repeated injection of low doses of bacterial superantigens (SAg) is known to induce specific T cell unresponsiveness. We show in this study that the spleen of BALB/c mice receiving chronically, staphylococcal enterotoxin B (SEB) contains SEB-specific CD4+ TCRBV8+ T cells exerting an immune regulatory function on SEB-specific primary T cell responses. Suppression affects IL-2 and IFN-γ secretion as well as proliferation of T cells. However, the suppressor cells differ from the natural CD4+ T regulatory cells, described recently in human and mouse, because they do not express cell surface CD25. They are CD152 (CTLA-4)-negative and their regulatory activity is not associated with expression of the NF Foxp3. By contrast, after repeated SEB injection, CD4+CD25+ splenocytes were heterogenous and contained both effector as well as regulatory cells. In vivo, CD4+CD25− T regulatory cells prevented SEB-induced death independently of CD4+CD25+ T cells. Nevertheless, SEB-induced tolerance could not be achieved in thymectomized CD25+ cell-depleted mice because repeated injection of SEB did not avert lethal toxic shock in these animals. Collectively, these data demonstrate that, whereas CD4+CD25+ T regulatory cells are required for the induction of SAg-induced tolerance, CD4+CD25− T cells exert their regulatory activity at the maintenance stage of SAg-specific unresponsiveness.
- Published
- 2003
45. Contributions of innate immunity to allograft rejection and survival
- Author
-
Alain Le Moine and Michel Goldman
- Subjects
Transplantation ,medicine.medical_specialty ,Innate immune system ,chemical and pharmacologic phenomena ,Inflammation ,Biology ,Acquired immune system ,Organ transplantation ,surgical procedures, operative ,Clinical evidence ,Allograft rejection ,Immunology ,Allograft survival ,medicine ,Immunology and Allergy ,medicine.symptom - Abstract
Experimental clinical evidence has highlighted the importance of early posttransplantation events in determining allograft survival. Graft inflammation is initiated by activation of cellular and humoral components of innate immunity in an antigen-independent manner. Subsequently, the alloreactive response is driven by donor-specific T-cell-dependent adaptive immunity. A positive cross-talk between innate and adaptive responses governs the magnitude of the host-versus-graft response. This article reviews recent studies on the cellular and molecular pathways through which innate immunity may trigger allograft rejection. Curr Opin Organ Transplant 2003, 8:2-6. © 2003 Lippincott Williams & Wilkins.
- Published
- 2003
46. Skin Graft Rejection Elicited by β2-Microglobulin as a Minor Transplantation Antigen Involves Multiple Effector Pathways: Role of Fas-Fas Ligand Interactions and Th2-Dependent Graft Eosinophil Infiltrates
- Author
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Jean-Charles Guéry, Murielle Surquin, Nathalie Nagy, Patrick Stordeur, Michel Goldman, Alain Le Moine, François-Xavier Demoor, Daniel Abramowicz, Isabelle Salmon, Véronique Flamand, and Katia Rombaut
- Subjects
CD4-Positive T-Lymphocytes ,Cytotoxicity, Immunologic ,Graft Rejection ,Fas Ligand Protein ,Transplantation Conditioning ,CD8 Antigens ,Immunology ,CD8-Positive T-Lymphocytes ,Biology ,Ligands ,Fas ligand ,Minor Histocompatibility Antigens ,Mice ,Th2 Cells ,Antigen ,Cell Movement ,MHC class I ,medicine ,Animals ,Immunology and Allergy ,Cytotoxic T cell ,RNA, Messenger ,fas Receptor ,Mice, Knockout ,Membrane Glycoproteins ,Beta-2 microglobulin ,Antibodies, Monoclonal ,Skin Transplantation ,Eosinophil ,Molecular biology ,Eosinophils ,Mice, Inbred C57BL ,Transplantation ,medicine.anatomical_structure ,biology.protein ,Cytokines ,Female ,Lymph Nodes ,beta 2-Microglobulin ,Injections, Intraperitoneal ,Spleen ,CD8 ,Signal Transduction - Abstract
Beta(2)-microglobulin (beta(2)m)-derived peptides are minor transplantation Ags in mice as beta(2)m-positive skin grafts (beta(2)m(+/+)) are rejected by genetically beta(2)m-deficient recipient mice (beta(2)m(-/-)). We studied the effector pathways responsible for the rejection induced by beta(2)-microglobulin-derived minor transplantation Ags. The rejection of beta(2)m(+/+) skin grafts by naive beta(2)m(-/-) mice was dependent on both CD4 and CD8 T cells as shown by administration of depleting mAbs. Experiments performed with beta(2)m(-/-)CD8(-/-) double knockout mice grafted with a beta(2)m(+/+) MHC class I-deficient skin showed that sensitized CD4 T cells directed at beta(2)m peptides-MHC class II complexes are sufficient to trigger rapid rejection. Rejection of beta(2)m(+/+) grafts was associated with the production of IL-5 in vitro, the expression of IL-4 and IL-5 mRNAs in the grafted tissue, and the presence within rejected grafts of a considerable eosinophil infiltrate. Blocking IL-4 and IL-5 in vivo and depleting eosinophils with an anti-CCR3 mAb prevented graft eosinophil infiltration and prolonged beta(2)m(+/+) skin graft survival. Lymphocytes from rejecting beta(2)m(-/-) mice also displayed an increased production of IFN-gamma after culture with beta(2)m(+/+) minor alloantigens. In vivo neutralization of IFN-gamma inhibited skin graft rejection. Finally, beta(2)m(+/+) skin grafts harvested from B6(lpr/lpr) donor mice, which lack a functional Fas molecule, survived longer than wild-type beta(2)m(+/+) skin grafts, showing that Fas-Fas ligand interactions are involved in the rejection process. We conclude that IL-4- and IL-5-dependent eosinophilic rejection, IFN-gamma-dependent mechanisms, and Fas-Fas ligand interactions are effector pathways in the acute rejection of minor transplantation Ags.
- Published
- 2002
47. Multiple pathways to allograft rejection
- Author
-
Michel Goldman, Alain Le Moine, and Daniel Abramowicz
- Subjects
Graft Rejection ,Isoantigens ,Granulocyte activation ,Chemokine ,Leukocyte migration ,T-Lymphocytes ,chemical and pharmacologic phenomena ,Immune system ,Transplantation Immunology ,Animals ,Humans ,Transplantation, Homologous ,Medicine ,Cell adhesion ,Antigen-presenting cell ,Transplantation ,Innate immune system ,biology ,business.industry ,Complement system ,surgical procedures, operative ,Immune System ,Immunology ,biology.protein ,Chemokines ,business - Abstract
Allograft rejection results from a complex process involving both the innate and acquired immune systems. The innate immune system predominates in the early phase of the allogeneic response, during which chemokines and cell adhesion play essential roles, not only for leukocyte migration into the graft but also for facilitating dendritic and T-cell trafficking between lymph nodes and the transplant. This results in a specific and acquired alloimmune response mediated by T cells. Subsequently, T cells and cells from innate immune system function synergistically to reject the allograft through nonexclusive pathways, including contact-dependent T cell cytotoxicity, granulocyte activation by either Th1 or Th2 derived cytokines, NK cell activation, alloantibody production, and complement activation. Blockade of individual pathways generally does not prevent allograft rejection, and long-term allograft survival is achieved only after simultaneous blockade of several of them. In this review, we explore each of these pathways and discuss the experimental evidence highlighting their roles in allograft rejection.
- Published
- 2002
48. TO020SHOULD WE DISCONTINUE CYCLOSPORIN OR STEROIDS IN RENAL TRANSPLANTATION? FIVE YEAR OUTCOME RESULTS OF THE CISTCERT TRIAL
- Author
-
Alain Le Moine, M Wissing, Nilufer Broeders, Jean-Louis Bosmans, Laurent Weekers, Steven Van Laecke, Daniel Abramowicz, Jacques Sennesael, and Patrick Peeters
- Subjects
Transplantation ,Pediatrics ,medicine.medical_specialty ,Nephrology ,business.industry ,medicine ,business ,Outcome (game theory) - Published
- 2017
49. A role for eosinophils in transplant rejection
- Author
-
Michel Y Braun, Alain Le Moine, Daniel Abramowicz, Michel Goldman, and Véronique Flamand
- Subjects
Graft Rejection ,T cell ,Immunology ,Inflammation ,CD8-Positive T-Lymphocytes ,Pathogenesis ,Mice ,Th2 Cells ,Eosinophilia ,medicine ,Animals ,Immunology and Allergy ,Interleukin 9 ,Interleukin 5 ,Interleukin 4 ,business.industry ,Interleukin-9 ,respiratory system ,Eosinophil ,medicine.disease ,Transplant rejection ,Eosinophils ,medicine.anatomical_structure ,Interleukin-4 ,Interleukin-5 ,medicine.symptom ,business - Abstract
Eosinophils release inflammatory mediators and cationic proteins that are instrumental in the pathogenesis of allergic diseases such as bronchial asthma. Here, we review experimental observations indicating that eosinophils are also involved in the rejection of allografts. We propose that their role as effectors of transplant damage becomes crucial when classical pathways of rejection are inhibited and T helper 2 (Th2) cells dominate the alloimmune response.
- Published
- 2001
50. Ticlopidine and clopidogrel, sometimes combined with aspirin, only minimally increase the surgical risk in renal transplantation: a case-control study
- Author
-
Claude Sadis, Judith Racapé, Lidia Ghisdal, Alain Le Moine, M Wissing, Annick Massart, Dimitri Mikhalski, Daniel Abramowicz, Nilufer Broeders, Ahmed Benahmed, Vincent Donckier, Mireille N Kianda, Anh Dung Hoang, Philippe Madhoun, Anne Lemy, and Basic (bio-) Medical Sciences
- Subjects
Male ,Risk ,medicine.medical_specialty ,Ticlopidine ,Time Factors ,Blood Loss, Surgical ,Postoperative Complications ,Risk Factors ,medicine ,Journal Article ,Humans ,cardiovascular diseases ,Survival rate ,Kidney transplantation ,Retrospective Studies ,Transplantation ,Aspirin ,Dose-Response Relationship, Drug ,business.industry ,Research Support, Non-U.S. Gov't ,Incidence ,Graft Survival ,Retrospective cohort study ,Middle Aged ,Clopidogrel ,medicine.disease ,Prognosis ,Kidney Transplantation ,Surgery ,Survival Rate ,surgical procedures, operative ,Nephrology ,Anesthesia ,Case-Control Studies ,Platelet aggregation inhibitor ,Kidney Failure, Chronic ,Drug Therapy, Combination ,Female ,business ,Platelet Aggregation Inhibitors ,circulatory and respiratory physiology ,medicine.drug ,Follow-Up Studies - Abstract
BACKGROUND: Patients undergoing kidney transplantation are sometimes being treated with antiplatelet agents such as ticlopidine or clopidogrel. Some teams refuse to wait-list these patients for fear of bleeding during transplant surgery. METHODS: We retrospectively reviewed the records of 702 adult patients with a kidney transplant alone between 2000 and 2010. Nineteen (2.7%) patients were taking clopidogrel or ticlopidine when called in for transplantation. Furthermore, 10 of these 19 patients were also taking low-dose aspirin (ASA). We compared the risk of bleeding peri- and postoperatively, and the occurrence of cardiovascular complications within 30 days after renal transplantation between 19 cases and 39 controls randomly selected within the cohort. RESULTS: Platelets were administered to 7 cases (37%) versus 0 controls (P
- Published
- 2013
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