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Immune phenotype predicts new onset diabetes after kidney transplantation
Authors:Didier Ducloux  Cécile Courivaud  Jamal Bamoulid  Thomas Crepin  Emilie Gaiffe  Caroline Laheurte  Charline Vauchy  Jean-Michel Rebibou  Philippe Saas  Sophie Borot
Affiliation:1. INSERM, UMR1098, Federation Hospitalo-universitaire INCREASE, Besançon F-25000, France;2. Univ. Bourgogne Franche-Comté, Faculté de Médecine et de Pharmacie, Besançon, LabEx LipSTIC, F-25000, France;3. Structure Fédérative de Recherche, SFR FED4234, Besançon F-25000, France;4. CHU Besançon, Department of Nephrology, Dialysis, and Renal Transplantation, F-25000 Besançon, France;5. CHU Besançon, CIC Biothérapie, INSERM CIC1431, F-25000 Besançon, France,;6. EFS Bourgogne Franche-Comté, Plateforme de Biomonitoring, CIC 1431/UMR1098, Besançon F-25000, France;7. CHU Dijon, Department of Nephrology, Dialysis, and Renal Transplantation, 21000 Dijon, France;8. CHU Besançon, Department of Diabetology and Endocrinology, F-25000 Besançon, France
Abstract:
Few data are available concerning immune factors involved in the occurrence of new onset diabetes after transplantation (NODAT). Our objective was to determine an immune profile associated with the subsequent development of NODAT. The secondary objective was to build a predictive model of NODAT. We studied a prospective cohort of incident kidney transplant patients to determine whether pre-transplant immune characteristics could be associated with the occurrence of NODAT. 818 patients were included. We observed a significant inverse correlation between BMI and recent thymic emigrants (RTE) % at transplant time (p < 0.001). 177 (17.3%) of 677 non-diabetic patients experienced NODAT in the first year post-transplant. In multivariate analysis, age, body mass index (BMI), use of Tacrolimus, use of anti-thymocyte globulins (ATG), higher B cell count, and lower recent thymic emigrants (RTE) % were associated with NODAT. A differential effect of immune profile was observed in ATG-treated patients and non-ATG-treated patients. B cell count predicts NODAT only in non-ATG-treated patients whereas lower RTE% was associated with NODAT only in ATG-treated patients. Tacrolimus sparing and B cell depletion may efficiently prevent NODAT in selected patients. We identified an immune profile associated with the occurrence of post-transplant diabetes. Further studies should better precise the exact mechanisms involved in this association. Trial registration NCT02843867, registered July 8, 2016 – retrospectively registered https://clinicaltrials.gov/ct2/show/record/NCT02843867.
Keywords:Corresponding author at: Department of Nephrology, Dialysis, and Renal Transplantation, F-25030 Besançon, France.  Immunosuppressive therapy  Kidney transplantation  New onset diabetes  Prediction model  Immune responses  ATG  anti-thymocytes globulins  BMI  body mass index  CMV  Cytomegalovirus  PRA  panel reactive antibody  NODAT  new onset diabetes after transplantation  RTE  recent thymic emigrants
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