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1. History of bariatric surgery and COVID-19 outcomes in patients with type 2 diabetes: Results from the CORONADO study

Author

Natacha Germain, Matthieu Wargny, François Pattou, Claire Blanchard, Sophie Borot, Lyse Bordier, Dominique Seret-Bégué, Edith Bigot-Corbel, Bruno Vergès, Bertrand Cariou, Christine Coffin-Boutreux, Céline Gonfroy-Leymarie, Olivier Bourron, Laurent Meyer, Ronan Roussel, Pierre Gourdy, Gaëtan Prévost, Béatrice Guyomarch, Anne Dutour, Charles Thivolet, Matthieu Pichelin, Tanguy Perennec, Blandine Tramunt, Sarra Smati, Samy Hadjadj, Cyrielle Caussy, CarMeN, laboratoire, Institut des maladies de l'appareil digestif [Nantes] (IMAD), Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Hôpital d'Instruction des Armées Begin, Service de Santé des Armées, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hospices Civils de Lyon (HCL), CENTRE HOSPITALIER PÉRIGUEUX (CHP), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Saint-Etienne, Université Jean Monnet - Saint-Étienne (UJM), Centre Hospitalier René Dubos [Pontoise], Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, Département d'Endocrinologie, Diabète et Maladies Métaboliques [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier de Gonesse (CHU Gonesse), Service d'Endocrinologie, Diabétologie et Maladies Métaboliques (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Recherche translationnelle sur le diabète - U 1190 (RTD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), FCRIN/FORCE Network, Centre d'investigation clinique (CIC) de Nantes -CIC Plurithématique (CIC 0004 - Nantes), Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), École Pratique des Hautes Études (EPHE), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)

Subjects
Diabetes duration, medicine.medical_specialty, animal structures, Coronavirus disease 2019 (COVID-19), Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Bariatric Surgery, Type 2 diabetes, Endocrinology, COVID‐19, Diabetes mellitus, medicine, Humans, In patient, Viral, Brief Cutting Edge Report, Retrospective Studies, Mechanical ventilation, Diabetes Mellitus, Nutrition and Dietetics, business.industry, SARS-CoV-2, COVID-19, medicine.disease, Surgery, Type 2 Diabetes, [SDV] Life Sciences [q-bio], Metabolic and Bariatric Surgery, Diabetes Mellitus, Type 2, covid-19, RNA, Viral, RNA, Observational study, business, Body mass index, Type 2
Abstract

International audience; OBJECTIVE: This study assessed the impact of a history of metabolic and bariatric surgery (MBS) on the clinical outcomes in patients with type 2 diabetes (T2D) and severe obesity hospitalized for COVID-19. METHODS: In this post hoc analysis from the nationwide observational CORONADO (Coronavirus SARS-CoV2 and Diabetes Outcomes) study, patients with T2D and a history of MBS were matched with patients without MBS for age, sex, and BMI either at the time of MBS or on admission for COVID-19. The composite primary outcome (CPO) combined invasive mechanical ventilation and/or death within 7 and 28 days following admission. RESULTS: Out of 2,398 CORONADO participants, 20 had a history of MBS. When matching for BMI at the time of MBS and after adjustment for diabetes duration, the CPO occurred less frequently within 7 days (3 vs. 17 events, OR: 0.15 [0.01 to 0.94], p = 0.03) and 28 days (3 vs. 19 events, OR: 0.11 [0.01 to 0.71], p = 0.02) in patients with MBS (n = 16) vs. controls (n = 44). There was no difference in CPO rate between patients with MBS and controls when matching for BMI on admission. CONCLUSIONS: These data are reassuring regarding COVID-19 prognosis in patients with diabetes and a history of MBS compared with those without MBS.

Published
2022
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2. Early recognition of cardiac surgery-associated acute kidney injury: lack of added value of TIMP2 IGFBP7 over short-term changes in creatinine (an observational pilot study)

Author

Edith Bigot-Corbel, Arnaud Legrand, Lucile Figueres, Floris Chabrun, Thomas Senage, Karim Lakhal, Émilie Sacchetto, Bertrand Rozec, Maxime Leroy, Hôpital Guillaume-et-René-Laennec [Saint-Herblain], MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Hôtel-Dieu de Nantes, Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Malbec, Odile

Subjects
Male, Tissue inhibitor of Metalloproteinase-2/urine* [MeSH], [SDV]Life Sciences [q-bio], Pilot Projects, law.invention, chemistry.chemical_compound, 0302 clinical medicine, Aortic valve replacement, 030202 anesthesiology, law, Anesthesiology, RD78.3-87.3, Prospective Studies, Aged, 80 and over, Heart Valve Prosthesis Implantation, Cardiopulmonary Bypass, biology, Acute kidney injury, Insulin-like growth factor binding proteins/urine* [MeSH], Acute Kidney Injury, Cardiac surgery, [SDV] Life Sciences [q-bio], Insulin-Like Growth Factor Binding Proteins, Creatinine/blood [MeSH], Lipocalins/metabolism* [MeSH], 030220 oncology & carcinogenesis, Aortic Valve, Cardiac surgical procedures [MeSH], Female, medicine.medical_specialty, Urology, Context (language use), Sensitivity and Specificity, 03 medical and health sciences, medicine, Cardiopulmonary bypass, Humans, Acute kidney injury [MeSH], Cystatin C, Aged, Creatinine, Tissue Inhibitor of Metalloproteinase-2, business.industry, Research, Perioperative, medicine.disease, Anesthesiology and Pain Medicine, Early Diagnosis, chemistry, biology.protein, business, Tissue inhibitor of Metalloproteinase-2 [MeSH], Biomarkers
Abstract

Background For the detection of cardiac surgery-associated acute kidney injury (CS-AKI), the performance of urine tissue inhibitor of metalloproteinase 2 insulin-like growth factor-binding protein 7 (TIMP2 IGFBP7) has never been compared with that of very early changes in plasma creatinine (∆pCr). We hypothesized that, in the context of perioperative haemodilution, lack of postoperative decrease in pCr would be of honourable performance for the detection of CS-AKI. We therefore aimed at comparing these biomarkers and their kinetics (primary objective). As secondary objectives, we assessed plasma neutrophil gelatinase-associated lipocalin (pNGAL), cystatin C (pCysC) and urea (pUrea). We also determined the ability of these biomarkers to early discriminate persistent from transient CS-AKI. Methods Patients over 75 years-old undergoing aortic valve replacement with cardiopulmonary bypass (CPB) were included in this prospective observational study. Biomarkers were measured before/after CPB and at the sixth postoperative hour (H6). Results In 65 patients, CS-AKI occurred in 27 (42%). ∆pCr from post-CPB to H6 (∆pCrpostCPB-H6): outperformed TIMP2 IGFBP7 at H6 and its intra- or postoperative changes: area under the receiver operating characteristic curve (AUCROC) of 0.84 [95%CI:0.73–0.92] vs. ≤0.67 [95%CI:0.54–0.78], p ≤ 0.03. The AUCROC of pNGAL, pCysC and pUrea did not exceed 0.72 [95%CI:0.59–0.83]. Indexing biomarkers levels for blood or urine dilution did not improve their performance. Combining TIMP2 IGFBP7 and ∆pCrpostCPB-H6 was of no evident added value over considering ∆pCrpostCPB-H6 alone. For the early recognition of persistent CS-AKI, no biomarker outperformed ∆pCrpostCPB-H6 (AUCROC = 0.69 [95%CI:0.48–0.85]). Conclusions In this hypothesis-generating study mostly testing early detection of mild CS-AKI, there was no evident added value of the tested modern biomarkers over early minimal postoperative changes in pCr: despite the common perioperative hemodilution in the setting of cardiac surgery, if pCr failed to decline within the 6 h after CPB, the development of CS-AKI was likely. Confirmatory studies with more severe forms of CS-AKI are required.

Published
2021
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3. Comparison of Monoclonal Gammopathies Linked to Poliovirus or Coxsackievirus vs. Other Infectious Pathogens

Author

Adrien Bosseboeuf, Philippe Moreau, Caroline Moreau, Olivier Decaux, Valéry Salle, Anne Tallet, Margaux Louvois, Cassandra Lepetit, Sylvie Hermouet, Maeva Fourny, Nicolas Mennesson, Edith Bigot-Corbel, Jean Harb, Sophie Allain-Maillet, Eric Piver, Molecular Mechanisms of Chronic Inflammation in Hematological Diseases (CRCINA-ÉQUIPE 16), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Université de Nantes (UN)-Université de Nantes (UN), Laboratoire de Biochimie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], CHU Pontchaillou [Rennes], Laboratoire de Biochimie [Rennes], Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Laboratoire de Biochimie [CHRU Tours], Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, Service d'Hématologie [Nantes], CHU Amiens-Picardie, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Bernardo, Elizabeth

Subjects
0301 basic medicine, Adult, Microarray, Paraproteinemias, Coxsackievirus Infections, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Coxsackievirus, medicine.disease_cause, Epitope, Article, 03 medical and health sciences, 0302 clinical medicine, Antigen, [SDV.CAN] Life Sciences [q-bio]/Cancer, hemic and lymphatic diseases, medicine, Humans, Multiplex, lcsh:QH301-705.5, Aged, Retrospective Studies, Aged, 80 and over, coxsackievirus, poliovirus, monoclonal immunoglobulin, Poliovirus, monoclonal gammopathy, General Medicine, MGUS, multiple myeloma, infection, pathogen, antigen specificity, Middle Aged, medicine.disease, biology.organism_classification, Virology, 3. Good health, 030104 developmental biology, lcsh:Biology (General), 030220 oncology & carcinogenesis, Monoclonal, Monoclonal gammopathy of undetermined significance
Abstract

International audience; Chronic stimulation by infectious pathogens or self-antigen glucosylsphingosine (GlcSph) can lead to monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). Novel assays such as the multiplex infectious antigen microarray (MIAA) and GlcSph assays, permit identification of targets for >60% purified monoclonal immunoglobulins (Igs). Searching for additional targets, we selected 28 purified monoclonal Igs whose antigen was not represented on the MIAA and GlcSph assays; their specificity of recognition was then analyzed using microarrays consisting of 3760 B-cell epitopes from 196 pathogens. The peptide sequences PALTAVETG and PALTAAETG of the VP1 coat proteins of human poliovirus 1/3 and coxsackievirus B1/B3, respectively, were specifically recognized by 6/28 monoclonal Igs. Re-analysis of patient cohorts showed that purified monoclonal Igs from 10/155 MGUS/SM (6.5%) and 3/147 MM (2.0%) bound to the PALTAVETG or PALTAAETG epitopes. Altogether, PALTAV/AETG-initiated MGUS are not rare and few seem to evolve toward myeloma.

Published
2021
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4. Phenotypic Differences Between Polygenic and Monogenic Hypobetalipoproteinemia

Author

Sybil Charrière, Bertrand Cariou, Matthieu Pichelin, Alain Carrié, Noël Peretti, Richard Redon, Pierre Antoine Rollat-Farnier, Mathilde Di Filippo, René Valéro, Marie Marrec, Matthieu Wargny, Eléonore Divry, O. Marmontel, Edith Bigot-Corbel, X. Vanhoye, Pierre Lindenbaum, Philippe Moulin, Emmanuelle Génin, Antoine Rimbert, Dramane Coulibaly, Jean-François Deleuze, Gilles Degraef, Didier Goxe, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Hospices Civils de Lyon (HCL), Hôpital Louis Pradel [CHU - HCL], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Génomique d'Evry (IG), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Caisse primaire d'assurance maladie (CPAM), Centre hospitalier universitaire de Nantes (CHU Nantes), ANR-16-RHUS-0007,CHOPIN,CHOPIN(2016), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Biochimie Endocrinienne et Oncologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Adult, Male, Multifactorial Inheritance, hypobetalipoproteinemias, liver diseases, [SDV]Life Sciences [q-bio], Down-Regulation, 030204 cardiovascular system & hematology, Biology, Risk Assessment, Fifth percentile, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Risk Factors, medicine, Humans, Genetic Predisposition to Disease, Retrospective Studies, 030304 developmental biology, Lipoprotein cholesterol, Genetics, 0303 health sciences, Cholesterol, cholesterol, Cholesterol, LDL, medicine.disease, Phenotype, 3. Good health, chemistry, Apolipoprotein B-100, Mutation (genetic algorithm), polygenic risk score, Female, Polygenic risk score, Hypobetalipoproteinemia, Proprotein Convertase 9, mutation, Cardiology and Cardiovascular Medicine, apolipoproteins, Biomarkers
Abstract

Objective: Primary hypobetalipoproteinemia is characterized by LDL-C (low-density lipoprotein cholesterol) concentrations below the fifth percentile. Primary hypobetalipoproteinemia mostly results from heterozygous mutations in the APOB and PCSK9 genes, and a polygenic origin is hypothesized in the remaining cases. Hypobetalipoproteinemia patients present an increased risk of nonalcoholic fatty liver disease and steatohepatitis. Here, we compared hepatic alterations between monogenic, polygenic, and primary hypobetalipoproteinemia of unknown cause. Approach and Results: Targeted next-generation sequencing was performed in a cohort of 111 patients with hypobetalipoproteinemia to assess monogenic and polygenic origins using an LDL-C-dedicated polygenic risk score. Forty patients (36%) had monogenic hypobetalipoproteinemia, 38 (34%) had polygenic hypobetalipoproteinemia, and 33 subjects (30%) had hypobetalipoproteinemia from an unknown cause. Patients with monogenic hypobetalipoproteinemia had lower LDL-C and apolipoprotein B plasma levels compared with those with polygenic hypobetalipoproteinemia. Liver function was assessed by hepatic ultrasonography and liver enzymes levels. Fifty-nine percent of patients with primary hypobetalipoproteinemia presented with liver steatosis, whereas 21% had increased alanine aminotransferase suggestive of liver injury. Monogenic hypobetalipoproteinemia was also associated with an increased prevalence of liver steatosis (81% versus 29%, P Conclusions: This study highlights the importance of genetic diagnosis in the clinical care of primary hypobetalipoproteinemia patients. It shows for the first time that a polygenic origin of hypobetalipoproteinemia is associated with a lower risk of liver steatosis and liver injury versus monogenic hypobetalipoproteinemia. Thus, polygenic risk score is a useful tool to establish a more personalized follow-up of primary hypobetalipoproteinemia patients.

Published
2021
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5. An O-GlcNAcylomic Approach Reveals ACLY as a Potential Target in Sepsis in the Young Rat

Author

Didier Vertommen, Justine Dontaine, Charlotte Betus, Anaïs Maillard, Matthieu Rivière, Angélique Erraud, Thomas Pelé, Laurent Bultot, Jacques Lebreton, Benjamin Lauzier, Aurélia A. Leroux, Jérôme Montnach, A. Persello, M. Denis, Bertrand Rozec, Michel De Waard, Edith Bigot-Corbel, J. Dhot, Luc Bertrand, T. Dupas, Arnaud Tessier, Tessier, Arnaud, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Université Catholique de Louvain = Catholic University of Louvain (UCL), Sanofi Aventis R&D [Chilly-Mazarin], Centre hospitalier universitaire de Nantes (CHU Nantes), Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation (CEISAM), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Walloon Excellence in Life sciences and BIOtechnology [Liège] (WELBIO), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)

Subjects
Lipopolysaccharides, Lipopolysaccharide, ATP citrate lyase, [SDV]Life Sciences [q-bio], Stimulation, chemistry.chemical_compound, 0302 clinical medicine, O-GlcNAcylation, Biology (General), Spectroscopy, mass spectrometry, 0303 health sciences, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Acetylation, General Medicine, Shock, Septic, 3. Good health, Computer Science Applications, [SDV] Life Sciences [q-bio], Chemistry, Shock (circulatory), medicine.symptom, medicine.medical_specialty, Mean arterial pressure, QH301-705.5, Catalysis, Article, Acetylglucosamine, Inorganic Chemistry, Sepsis, 03 medical and health sciences, O-GlcNAcylomics, children, Internal medicine, medicine, Animals, Physical and Theoretical Chemistry, QD1-999, Molecular Biology, 030304 developmental biology, Septic shock, business.industry, Organic Chemistry, medicine.disease, [CHIM.ORGA] Chemical Sciences/Organic chemistry, Rats, Endocrinology, Blood pressure, chemistry, ATP Citrate (pro-S)-Lyase, Fluid Therapy, septic shock, business, Protein Processing, Post-Translational, 030217 neurology & neurosurgery
Abstract

Sepsis in the young population, which is particularly at risk, is rarely studied. O-GlcNAcylation is a post-translational modification involved in cell survival, stress response and metabolic regulation. O-GlcNAc stimulation is beneficial in adult septic rats. This modification is physiologically higher in the young rat, potentially limiting the therapeutic potential of O-GlcNAc stimulation in young septic rats. The aim is to evaluate whether O-GlcNAc stimulation can improve sepsis outcome in young rats. Endotoxemic challenge was induced in 28-day-old rats by lipopolysaccharide injection (E. Coli O111:B4, 20 mg·kg−1) and compared to control rats (NaCl 0.9%). One hour after lipopolysaccharide injection, rats were randomly assigned to no therapy, fluidotherapy (NaCl 0.9%, 10 mL·kg−1) ± NButGT (10 mg·kg−1) to increase O-GlcNAcylation levels. Physiological parameters and plasmatic markers were evaluated 2h later. Finally, untargeted mass spectrometry was performed to map cardiac O-GlcNAcylated proteins. Lipopolysaccharide injection induced shock with a decrease in mean arterial pressure and alteration of biological parameters (p &lt, 0.05). NButGT, contrary to fluidotherapy, was associated with an improvement of arterial pressure (p &lt, 0.05). ATP citrate lyase was identified among the O-GlcNAcylated proteins. In conclusion, O-GlcNAc stimulation improves outcomes in young septic rats. Interestingly, identified O-GlcNAcylated proteins are mainly involved in cellular metabolism.

Published
2021
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6. Bile acids associate with glucose metabolism, but do not predict conversion from impaired fasting glucose to diabetes

Author

Matthieu Pichelin, Marielle Joliveau, Edith Bigot-Corbel, Amandine Descat, Bart Staels, Oscar Chávez-Talavera, Rémy Hanf, Cédric Le May, Jean-François Goossens, Emmanuelle Vallez, Samy Hadjadj, Mostafa Kouach, Matthieu Wargny, Bertrand Cariou, Anne Tailleux, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Derudas, Marie-Hélène, EGID Diabetes Pole - - EGID2010 - ANR-10-LABX-0046 - LABX - VALID, Infrastructure Française de Protéomique - - ProFI2010 - ANR-10-INBS-0008 - INBS - VALID, Bile acid, immune-metabolism, lipid and glucose homeostasis - ImmunoBile - - H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) 2016-09-01 - 2021-08-31 - 694717 - VALID, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Unité de recherche de l'institut du thorax (ITX-lab), Université de Lille, Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Molecular Mechanisms of Chronic Inflammation in Hematological Diseases (CRCINA-ÉQUIPE 16), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Genfit SA [Loos, France], Entreprise biopharmaceutique GENFIT Loos, ANR-10-LABX-0046,EGID,EGID Diabetes Pole(2010), ANR-10-INBS-0008,ProFI,Infrastructure Française de Protéomique(2010), European Project: 694717,H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) ,ImmunoBile(2016), Le May, Cedric, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)

Subjects
Male, liquid chromatography tandem mass spectrometry, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Endocrinology, Diabetes and Metabolism, ECLIA, Takeda G protein coupled Receptor 5, UDCA, electrochemiluminescent enzyme immunoassay, hazard ratio, 0302 clinical medicine, Endocrinology, SFSTP, Chenodeoxycholic acid, CYP, HR, 6α-OH, Glucose homeostasis, fasting plasma glucose, HCA, Relationship between Insulin Sensitivity and Cardiovascular disease cohort, T2D, Prospective Studies, cholesterol associated with low density lipoproteins, 6α-hydroxylated, DCA, triglycerides, ComputingMilieux_MISCELLANEOUS, NOD, LCA, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, cholic acid, [SDV] Life Sciences [q-bio], FPG, cholesterol associated with high density lipoproteins, FXR, deoxycholic acid, Disease Progression, CYP27A1, ANR, 7α-hydroxy-4-cholesten-3-one, standard deviation, non-diabetic group, CYP cholesterol 27α-hydroxylase, medicine.medical_specialty, high molecular weight, interquartile range, IFG, Carbohydrate metabolism, HDCA, 03 medical and health sciences, Agence Nationale pour la Recherche, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Glucose Intolerance, tandem mass spectrometry, MS/MS, Humans, LC-MS/MS, 12α-hydroxylated, Aged, C4, methanol, SD, CYP cholesterol 7α-hydroxylase, medicine.disease, MeOH, HMW, hyocholic acid, Bile acids, 030104 developmental biology, Glucose, chemistry, Diabetes Mellitus, Type 2, glucagon-like peptide-1, homeostasis model assessment of insulin resistance, IR, CDCA, LDL-c, GLP-1, Prediabetes, Biomarkers, farnesoid X receptor, 0301 basic medicine, CYP7A1, [SDV]Life Sciences [q-bio], Société Française des Sciences et Techniques Pharmaceutiques, Type 2 diabetes, HOMA-IR, Bile acids Impaired fasting glucose Prediabetes New onset diabetes Hyocholic acid C4 HOMA-IR 12α-OH, BAs, Cohort Studies, chemistry.chemical_compound, impaired fasting glucose, insulin resistance, new onset diabetes, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, CA, IQR, TGR5, total cholesterol, RISC, Middle Aged, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, ursodeoxycholic acid, lithocholic acid, Female, chenodeoxycholic acid, HDL-c, TG, type 2 diabetes, TC, Adult, cytochrome P450, 030209 endocrinology & metabolism, body mass index, Bile Acids and Salts, Prediabetic State, BMI, Insulin resistance, Predictive Value of Tests, Internal medicine, Diabetes mellitus, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], HbA 1C, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Impaired fasting glucose, hyodeoxycholic acid, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, ND, business, Follow-Up Studies, glycated hemoglobin
Abstract

International audience; Objective: Bile acids (BAs) are signaling molecules controlling lipid and glucose metabolism. Since BA alterations are associated with obesity and insulin resistance, plasma BAs have been considered candidates to predict type 2 diabetes (T2D) risk. We aimed to determine (1) the association of BAs with glucose homeostasis parameters and (2) their predictive association with the risk of conversion from prediabetes to new-onset diabetes (NOD) in a prospective cohort study. Design: 205 patients with impaired fasting glucose (IFG) were followed each year during 5 years in the IT-DIAB cohort study. Twenty-one BA species and 7α-hydroxy-4-cholesten-3-one (C4), a marker of BA synthesis, were quantified by LC/MS-MS in plasma from fasted patients at baseline. Correlations between plasma BA species and metabolic parameters at baseline were assessed by Spearman's coefficients and the association between BAs and NOD was determined using Cox proportional-hazards models. Results: Among the analyzed BA species, total hyocholic acid (HCA) and the total HCA/total chenodeoxycholic acid (CDCA) ratio, reflecting hepatic BA 6α-hydroxylation activity, negatively correlated with BMI and HOMA-IR. The total HCA/total CDCA ratio also correlated negatively with HbA 1C. Conversion from IFG to NOD occurred in 33.7% of the participants during the follow-up. Plasma BA species were not independently associated with the conversion to NOD after adjustment with classical T2D risk factors. Conclusions: Fasting plasma BAs are not useful clinical biomarkers for predicting NOD in patients with IFG. However, an unexpected association between 6α-hydroxylated BAs and glucose parameters was found, suggesting a role for this specific BA pathway in metabolic homeostasis. IT-DIAB study registry number: NCT01218061.

Published
2020
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7. Anti-Infectious Pathogen Specificity of Purified Monoclonal Immunoglobulins from Patients with MGUS and Multiple Myeloma

Author

Eric Piver, François Girodon, Jean-Christophe Pages, Edith Bigot-Corbel, Cathy Charlier, Delphine Feron, Sylvie Hermouet, Jean Harb, Adrien Bosseboeuf, Pierre Weigel, Laurent Garderet, Philippe Moreau, Cédric Rossi, Anne Tallet, Valéry Salle, Denis Caillot, Molecular Mechanisms of Chronic Inflammation in Hematological Diseases (CRCINA-ÉQUIPE 16), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Laboratoire de Biochimie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Unité de fonctionnalité et ingénierie de protéines (UFIP), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service d'hématologie biologique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre de ressources biologiques Ferdinand Cabanne [Dijon] (CRB Ferdinand Cabanne), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie Clinique (CHU de Dijon), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Unité de Biotechnologie, Biocatalyse et Biorégulation (U3B), Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Etablissement Français du Sang, Haut Conseil des Biotechnologies (HCB), Université de Tours (UT), Laboratoire de Biochimie [CHRU Tours], Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Service d'Hématologie [Nantes], Service d'hématologie biologique [CHU de Dijon], Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École Pratique des Hautes Études (EPHE), and UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)

Subjects
Hepatitis C virus, [SDV]Life Sciences [q-bio], Immunology, Varicella zoster virus, Cell Biology, Hematology, Biology, medicine.disease, medicine.disease_cause, Biochemistry, Virology, Herpesviridae, Virus, Lymphoma, Antigen, hemic and lymphatic diseases, medicine, biology.protein, Antibody, Multiple myeloma
Abstract

Background: Multiple myeloma (MM) is characterized by the accumulation of malignant plasma cells, which secrete >30g/L of monoclonal immunoglobulin (mc Ig). MM is always preceded by the usually asymptomatic stage called "monoclonal gammapathy of undetermined significance" (MGUS). Presently the detection of a mc Ig does not lead to analysis of its specificity of antigen (Ag) recognition. Yet certain infectious pathogens are associated with the development of B-cell malignancy: for instance, Epstein-Barr virus (EBV) and Burkitt lymphoma, Helicobacter pylori (H. pylori) and MALT lymphoma. Objective: Our aim was to determine the frequency of recognition by purified mc Ig from MGUS and MM patients, of infectious pathogens associated with chronic infection and B-cell malignancy. Methods: We used the "Multiplex Infectious Antigen Array" (MIAA)test set up by the team to study the specificity of purified mc IgG against 8 infectious pathogens: hepatitis C virus (HCV), EBV, H. pylori, varicella zoster virus (VZV), cytomegalovirus (CMV), herpesvirus simplex 1 (HSV-1), HSV-2, and Toxoplasma gondii. Second or third methods were used to verify the specificity of mc IgG (western blotting, ELISA, or another multiplex array). Sialylation of mc Ig, which reflects chronic inflammation, was also studied, via ELISAs and Western blotting, for 98 MGUS and MM patients and 43 controls. Results: The specificity of purified mc IgG was analyzed for 291 patients (60 MGUS, including 4 associated with a B-cell lymphoma; 108 MM; for the 123 other patients the diagnosis of MGUS or MM was not available). Purified mc IgG were found to be specific for one of the 8 infectious pathogens of the MIAA test for 17.5% of patients (51/291: 25 MGUS, 1 SMM, and 25 MM). Purified mc Ig specifically recognized EBV (n=27, including 8 MGUS, 1 SMM and 18 MM ; the Ag recognized were EBNA-1, 25 cases; and VCA, 2 cases); HCV (10 cases: 9 MGUS and 1 MM) ; HSV-1 (7 cases: 5 MGUS including 3 associated with a B-cell malignancy, and 2 MM) ; H. pylori (5 cases: 2 MGUS including 1 associated with a B-cell malignancy, and 3 MM); VZV (1 MM); and CMV (1 MGUS). The Ag most frequently recognized by purified mc IgG was EBV EBNA-1; MM patients with EBNA-1-specific mc IgG represented 10% of the MM in this series. Consistent with a pro-inflammatory effect, for 81.6% of MGUS and MM patients (80/98), the purified mc IgG was found to be hyposialylated. Moreover, purified polyclonal Ig were also hyposialylated for 37% of MM (compared to Conclusion: At least 6 infectious pathogens (EBV, HCV, H. pylori, HSV, VZV, CMV) may be involved in the pathogenesis of MGUS and MM with mc IgG. Importantly, EBV, HCV, H. pylori and HSV are known as oncogenic pathogens associated with solid cancer and/or B-cell malignancy. Finally, for 37% of the MM patients examined, both the polyclonal and mc Ig were found to be hyposialylated, which suggests that inflammation existed prior to clonality and MM. Disclosures Garderet: Takeda: Consultancy; Amgen: Consultancy; BMS: Consultancy, Honoraria; Novartis: Consultancy.

Published
2016
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8. Multiplexed infectious protein microarray immunoassay suitable for the study of the specificity of monoclonal immunoglobulins

Author

Edith Bigot-Corbel, Victor Gourain, Yannick Jacques, Cathy Charlier, Pierre Weigel, Delphine Feron, Patrice Le Pape, Sylvie Hermouet, Marianne Coste-Burel, Laurent Garderet, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Plateforme IMPACT, (FRE CNRS n°3478), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de virologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Parasitologie, Laboratoire de Biochimie Générale [Nantes], The study was supported by Grant 2010-088 from the Institut National du Cancer (INCa). INCa also financed the salary of D.F. (2011–2012)., and Bernardo, Elizabeth

Subjects
Adult, Male, Antibody microarray, Biophysics, Protein Array Analysis, Antibodies, Protozoan, Protein microarray, Enzyme-Linked Immunosorbent Assay, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antibodies, Viral, Biochemistry, Sensitivity and Specificity, Immunoglobulin G, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Antigen, medicine, Humans, Immune response, Fluorescent Antibody Technique, Indirect, Molecular Biology, 030304 developmental biology, 0303 health sciences, biology, medicine.diagnostic_test, Cell Biology, Middle Aged, Primary and secondary antibodies, Virology, Molecular biology, 3. Good health, Polyclonal antibodies, Virus Diseases, 030220 oncology & carcinogenesis, Immunoassay, Viruses, biology.protein, Infectious diseases, Female, Monoclonal immunoglobulin, Antibody, Toxoplasma, Toxoplasmosis
Abstract

International audience; Enzyme-linked immunosorbent assays (ELISAs) used to detect antibodies specific for common infectious agents such as Epstein–Barr virus (EBV), cytomegalovirus (CMV), Toxoplasma gondii (T. gondii), and hepatitis C virus (HCV) are time-consuming and require large volumes of samples, which restrict their use. We propose a new assay based on a multiplexed infectious protein (MIP) microarray combining different epitopes representative of the four germs. Antigens and lysates were printed on nitrocellulose slides to constitute the microarray. First, the microarray was incubated with human serum samples. Then, the suitability of the microarray for analysis of the specificity of purified monoclonal immunoglobulin (mc Ig) was assessed using serum and mc Ig of HCV-positive patients. Bound human immunoglobulin G (IgG) was detected using fluorescently labeled secondary antibodies, and the signals were quantified. Results obtained in serum samples with the new MIP microarray immunoassay were compared with ELI-SAs; we observed concordances of 95% for EBV, 93% for CMV, 91% for T. gondii, and 100% for HCV. Regarding purified mc Ig of HCV-positive patients, 3 of 3 recognized antigens printed on the microarray. Hence, the novel EBV/CMV/T. gondii/HCV MIP microarray allows simultaneous diagnosis of polyclonal and monoclonal immune response to infectious diseases using very small volume samples.

Published
2013
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9. Myocardial injury in coronavirus disease 19 (Covid-19): main pathophysiological mechanisms and clinical utility of cardiac biomarkers

Author

Kamel, Saïd, Raynor, Alexandre, Zozor, Samuel, Lacape, Geneviève, Brunel, Valéry, Nivet-Antoine, Valérie, Collin-Chavagnac, Delphine, Peoc’h, Katell, Cohen, Ariel, Lassoued, Amin Ben, Chévrier, Marc, Alemann, Mathieu, Lessinger, Jean-Marc, Bérard, Annie, Sapin, Vincent, Beauvieux, Marie-Christine, Levy, Pacifique, Lehmann, Sylvain, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Bordeaux [Bordeaux], CHU Rouen, Normandie Université (NU), Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Tenon [AP-HP], Thrombose, atherothrombose et pharmacologie appliquée, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Clermont-Ferrand, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Centre de résonance magnétique des systèmes biologiques (CRMSB), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Pour le Groupe de Travail de la SFBC « Marqueurs Biochimiques de la pathologie Covid-19 »: Isabelle Aimone-Gastin, Stéphanie Alcaraz, Stéphane Allouche, Malika Balduyck, Françoise Barbé, Yann Barguil, Jean-Philippe Bastard, Jean-Louis Beaudeux, Marie-Christine Beauvieux, Amin Ben Lassoued, Isabelle Benz de Bretagne, Annie Bérard, Laurent Bermont, Edith Bigot-Corbel, Muriel Bost, Valery Bourbonneux, Valery Brunel, Jean-Luc Carré, Camille Chenevier-Gobeaux, Marc Chevrier, Giulia Chinetti, Delphine Collin-Chavagnac, Hervé Delacour, Delphine Delevallée, François Desroys du Roure, Patrice Faure, Jean-Philippe Galhaud, Anne Galinier, Thierry Hauet, Carine Helj, Emilie Jolly, Said Kamel, Sylvain Lehmann, Aline Leroy, Jean-Marc Lessenger, Pacifique Levy, Anne-Marie Lorec-Penet, Samir Mesli, Dagui Monnet, Caroline Moreau, Laurence Mouly, Valérie Nivet-Antoine, Nathalie Oueidat, Mathieu Pecquet, Katell Peoc’h, Laurence Piéroni, Carole Poupon, Martine Roubille, Benoit Rucheton, Medhi Sakka, Vincent Sapin, Vincent Saunier, Florian Scherrer, François Schmitt, Sabine Zaepfel, Samuel Zozor

Subjects
myocardite, peptides natriurétiques, SARS-CoV-2, myocarde, [SDV]Life Sciences [q-bio], troponine, Covid-19
Abstract

International audience; Pour citer cet article : Atteintes myocardiques au cours de la maladie à coronavirus 19 (Covid-19) : principaux mécanismes physiopathologiques et utilité clinique des biomarqueurs cardiaques.

Published
2021
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10. Atteintes myocardiques au cours de la maladie à coronavirus 19 (Covid-19) : principaux mécanismes physiopathologiques et utilité clinique des biomarqueurs cardiaques

Author

Kamel, Saïd, Raynor, Alexandre, Zozor, Samuel, Lacape, Geneviève, Brunel, Valéry, Nivet-Antoine, Valérie, Collin-Chavagnac, Delphine, Peoc’h, Katell, Cohen, Ariel, Lassoued, Amin Ben, Chévrier, Marc, Alemann, Mathieu, Lessinger, Jean-Marc, Bérard, Annie, Sapin, Vincent, Beauvieux, Marie-Christine, Levy, Pacifique, Lehmann, Sylvain, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Bordeaux [Bordeaux], Université de Bordeaux (UB), Laboratoire de biochimie générale [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Innovations thérapeutiques en hémostase (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), CHU Necker - Enfants Malades [AP-HP], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Saint-Antoine [AP-HP], Thrombose, atherothrombose et pharmacologie appliquée, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Hôpital de la Timone [CHU - APHM] (TIMONE), Hospices Civils de Lyon (HCL), Nouvel Hôpital Civil de Strasbourg, Les Hôpitaux Universitaires de Strasbourg (HUS), Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Centre de résonance magnétique des systèmes biologiques (CRMSB), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Pour le Groupe de Travail de la SFBC « Marqueurs Biochimiques de la pathologie Covid-19 »: Isabelle Aimone-Gastin, Stéphanie Alcaraz, Stéphane Allouche, Malika Balduyck, Françoise Barbé, Yann Barguil, Jean-Philippe Bastard, Jean-Louis Beaudeux, Marie-Christine Beauvieux, Amin Ben Lassoued, Isabelle Benz de Bretagne, Annie Bérard, Laurent Bermont, Edith Bigot-Corbel, Muriel Bost, Valery Bourbonneux, Valery Brunel, Jean-Luc Carré, Camille Chenevier-Gobeaux, Marc Chevrier, Giulia Chinetti, Delphine Collin-Chavagnac, Hervé Delacour, Delphine Delevallée, François Desroys du Roure, Patrice Faure, Jean-Philippe Galhaud, Anne Galinier, Thierry Hauet, Carine Helj, Emilie Jolly, Said Kamel, Sylvain Lehmann, Aline Leroy, Jean-Marc Lessenger, Pacifique Levy, Anne-Marie Lorec-Penet, Samir Mesli, Dagui Monnet, Caroline Moreau, Laurence Mouly, Valérie Nivet-Antoine, Nathalie Oueidat, Mathieu Pecquet, Katell Peoc’h, Laurence Piéroni, Carole Poupon, Martine Roubille, Benoit Rucheton, Medhi Sakka, Vincent Sapin, Vincent Saunier, Florian Scherrer, François Schmitt, Sabine Zaepfel, Samuel Zozor, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Clermont-Ferrand, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), VIAUD, Karine, Normandie Université (NU)-Centre hospitalier universitaire de Rouen, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)

Subjects
Adult, Male, medicine.medical_specialty, Myocarditis, [SDV]Life Sciences [q-bio], Myocardial Infarction, troponine, Disease, Systemic inflammation, Predictive Value of Tests, Internal medicine, myocarde, Coagulopathy, medicine, myocardium, Humans, Hospital Mortality, Myocardial infarction, Pandemics, Aged, Aged, 80 and over, Endocarditis, biology, business.industry, SARS-CoV-2, troponin, Heart, General Medicine, Middle Aged, Prognosis, medicine.disease, Troponin, Pathophysiology, 3. Good health, myocardite, [SDV] Life Sciences [q-bio], peptides natriurétiques, biology.protein, Cardiology, Female, France, Myocardial infarction diagnosis, medicine.symptom, myocarditis, business, Covid-19, natriuretic peptides, Biomarkers
Abstract

International audience; Covid-19 is responsible for myocardial injury in many infected patients, which is associated with severe disease and critical illness. The mechanisms by which SARS-CoV-2 may cause myocardial damage involve direct effect of the virus in cardiac cells and indirect effect due to the clinical consequences of Covid-19. Cardiomyocytes are well known to express Angiotensin-Converting Enzyme-2 receptors (ACE-2) to facilitate the virus cell entry, which could explain the occurrence of myocarditis, functional alterations in the myocardium, and more rarely, myocardial infarction. Myocardial injury may also be secondary to systemic inflammation or coagulopathy due to complicated Covid-19. The existence of a cardio-intestinal axis with alteration of tryptophan metabolism in the small bowel leading first to colitis and then to systemic inflammation has also been evoked to explain the myocardial injury. Morphological and metabolic disturbances of the heart during the Covid-19 are associated with elevated concentrations of cardiac blood biomarkers, mainly troponins and natriuretic peptides. The determination of these biomarkers has proven to be very useful for diagnosis, prognosis, and risk stratification. Indeed, recent data demonstrated that about 20% of infected patients admitted to the hospital have elevated troponin or BNP levels, and Covid-19 patients with elevated troponin concentrations beyond the diagnostic threshold (99th percentile) were associated with a higher risk of in-hospital mortality. In conclusion, after more than a year of a unique global pandemic, it is now clearly established that myocardial injury during Covid-19 is frequent and strongly contributes to the severity of the disease. Cardiac alterations secondary to direct infection of cardiac cells by SARS-CoV-2 or to the clinical consequences of Covid-19 are associated with elevated levels of cardiac biomarkers in blood, whose measurement is crucial in clinical decision making.

Published
2021
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