title: Risk Factors for Type 1 Diabetes Recurrence in Immunosuppressed Recipients of Simultaneous Pancreas-Kidney Transplants.
abstract: Patients with type 1 diabetes (T1D) who are recipients of pancreas transplants are believed to rarely develop T1D recurrence in the allograft if effectively immunosuppressed. We evaluated a cohort of 223 recipients of simultaneous pancreas-kidney allografts for T1D recurrence and its risk factors. With long-term follow-up, recurrence was observed in approximately 7% of patients. Comparing the therapeutic regimens employed in this cohort over time, lack of induction therapy was associated with recurrence, but this occurs even with the current regimen, which includes induction; there was no influence of maintenance regimens. Longitudinal testing for T1D-associated autoantibodies identified autoantibody positivity, number of autoantibodies, and autoantibody conversion after transplantation as critical risk factors. Autoantibodies to the zinc transporter 8 had the strongest and closest temporal association with recurrence, which was not explained by genetically encoded amino acid sequence donor-recipient mismatches for this autoantigen. Genetic risk factors included the presence of the T1D-predisposing HLA-DR3/DR4 genotype in the recipient and donor-recipient sharing of HLA-DR alleles, especially HLA-DR3. Thus, T1D recurrence is not uncommon and is developing in patients treated with current immunosuppression. The risk factors identified in this study can be assessed in the transplant clinic to identify recurrent T1D and may lead to therapeutic advances.
authors: Diabetes Research Institute, Leonard Miller School of Medicine, University of Miami, Miami, FL.
authors: F
authors: F
authors: Vendrame
authors: Diabetes Research Institute, Leonard Miller School of Medicine, University of Miami, Miami, FL.
authors: Y-Y
authors: YY
authors: Hopfner
authors: Diabetes Research Institute, Leonard Miller School of Medicine, University of Miami, Miami, FL.|Department of Pediatrics, Leonard Miller School of Medicine, University of Miami, Miami, FL.
authors: S
authors: S
authors: Diamantopoulos
authors: Diabetes Research Institute, Leonard Miller School of Medicine, University of Miami, Miami, FL.
authors: S K
authors: SK
authors: Virdi
authors: Diabetes Research Institute, Leonard Miller School of Medicine, University of Miami, Miami, FL.
authors: G
authors: G
authors: Allende
authors: Diabetes Research Institute, Leonard Miller School of Medicine, University of Miami, Miami, FL.
authors: I V
authors: IV
authors: Snowhite
authors: Benaroya Research Institute, Seattle, WA.
authors: H K
authors: HK
authors: Reijonen
authors: Department of Surgery, Division of Transplantation, Leonard Miller School of Medicine, University of Miami, Miami, FL.
authors: L
authors: L
authors: Chen
authors: Department of Surgery, Division of Transplantation, Leonard Miller School of Medicine, University of Miami, Miami, FL.
authors: P
authors: P
authors: Ruiz
authors: Department of Surgery, Division of Transplantation, Leonard Miller School of Medicine, University of Miami, Miami, FL.
authors: G
authors: G
authors: Ciancio
authors: Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO.
authors: J C
authors: JC
authors: Hutton
authors: Department of Epidemiology and Public Health Sciences, Division of Biostatistics, Leonard Miller School of Medicine, University of Miami, Miami, FL.
authors: S
authors: S
authors: Messinger
authors: Diabetes Research Institute, Leonard Miller School of Medicine, University of Miami, Miami, FL.|Department of Surgery, Division of Transplantation, Leonard Miller School of Medicine, University of Miami, Miami, FL.
authors: G W
authors: GW
authors: Burke
authors: Diabetes Research Institute, Leonard Miller School of Medicine, University of Miami, Miami, FL.|Department of Medicine, Division of Endocrinology and Metabolism, Leonard Miller School of Medicine, University of Miami, Miami, FL.|Department of Microbiology and Immunology, Leonard Miller School of Medicine, University of Miami, Miami, FL.
authors: A
authors: A
authors: Pugliese
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000097:blood / Q000188:drug therapy / Q000209:etiology*; D006085:Graft Survival; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D016035:Pancreas Transplantation / Q000009:adverse effects*; D011183:Postoperative Complications; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors; D066027:Transplant Recipients; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D007166:Immunosuppressive Agents