Risk Factors for Type 1 Diabetes Recurrence in Immunosuppressed Recipients of Simultaneous Pancreas–Kidney Transplants

Autor: L. Chen, J. C. Hutton, Alberto Pugliese, Isaac Snowhite, George W. Burke, Gaetano Ciancio, Shari Messinger, Stavros Diamantopoulos, Philip Ruiz, Y. Y. Hopfner, Gloria Allende, Francesco Vendrame, S. K. Virdi, Helena Reijonen
Rok vydání: 2016
Předmět:
Graft Rejection
Male
Oncology
endocrine system diseases
medicine.medical_treatment
030230 surgery
Kidney Function Tests
Postoperative Complications
0302 clinical medicine
Recurrence
Risk Factors
immune system diseases
Immunology and Allergy
Pharmacology (medical)
Child
Kidney transplantation
Graft Survival
Immunosuppression
Clinical Science
Prognosis
3. Good health
Child
Preschool
Cohort
Original Article
Female
Pancreas Transplantation
Immunosuppressive Agents
Glomerular Filtration Rate
Adult
medicine.medical_specialty
Adolescent
030209 endocrinology & metabolism
Pancreas transplantation
Young Adult
03 medical and health sciences
Internal medicine
medicine
Humans
Autoantibodies
Immunosuppression Therapy
Transplantation
Type 1 diabetes
business.industry
Autoantibody
Infant
Original Articles
medicine.disease
Kidney Transplantation
Transplant Recipients
Regimen
Diabetes Mellitus
Type 1
Immunology
business
Follow-Up Studies
Zdroj: American Journal of Transplantation
ISSN: 1600-6135
DOI: 10.1111/ajt.13426
Popis: 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.
This study demonstrates that recurrence of islet autoimmunity and type 1 diabetes is a significant cause of immune‐mediated endocrine pancreas graft function in immunosuppressed recipients of simultaneous pancreas‐kidney transplants, and defines risk factors for this condition.
Databáze: OpenAIRE
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