ArticleDiabetes2010
Recurrence of type 1 diabetes after simultaneous pancreas-kidney transplantation, despite immunosuppression, is associated with autoantibodies and pathogenic autoreactive CD4 T-cells.
Article in Diabetes, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.
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Who cites it
108 citing papers in PubMed, 209 citations in OpenAlex.
- Alloantibody and autoantibody monitoring predicts islet transplantation outcome in human type 1 diabetes.Diabetes · 2013Trial
- Advantage of rapamycin over mycophenolate mofetil when used with tacrolimus for simultaneous pancreas kidney transplants: randomized, single-center trial at 10 years.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2012Trial
- Increased frequencies of myelin oligodendrocyte glycoprotein/MHC class II-binding CD4 cells in patients with multiple sclerosis.Journal of immunology (Baltimore, Md. : 1950) · 2011Trial
- Pancreatic tissue engineering: towards a vascularized bioengineered cure for diabetes.Frontiers in transplantation · 2026Review
- CXCL10 (IP-10) and anti-ZnT8 autoantibodies: Exploratory indicators of risk in pancreatic transplant rejection.Biomarker insights · 2025Article
- Cutting edge of immune response and immunosuppressants in allogeneic and xenogeneic islet transplantation.Frontiers in immunology · 2024Review
- Transplantation: platform to study recurrence of disease.Frontiers in immunology · 2024Article
- [Anesthesia for organ transplant patients].Die Anaesthesiologie · 2023Review
- Sterile Pancreas Inflammation during Preservation and after Transplantation.International journal of molecular sciences · 2023Review
- Impact of GAD65 and IA2 autoantibodies on islet allograft survival.Frontiers in clinical diabetes and healthcare · 2023Article
- Immune surveillance and humoral immune responses in kidney transplantation - A look back at T follicular helper cells.Frontiers in immunology · 2023Review
- The need and benefit of immune monitoring to define patient and disease heterogeneity, mechanisms of therapeutic action and efficacy of intervention therapy for precision medicine in type 1 diabetes.Frontiers in immunology · 2023Article
- Tolerogenic Delivery of a Hybrid Insulin Peptide Markedly Prolongs Islet Graft Survival in the NOD Mouse.Diabetes · 2022Article
- Designing biomaterials for the modulation of allogeneic and autoimmune responses to cellular implants in Type 1 Diabetes.Acta biomaterialia · 2021Review
- Hybrid computational modeling demonstrates the utility of simulating complex cellular networks in type 1 diabetes.PLoS computational biology · 2021Article
- First World Consensus Conference on pancreas transplantation: Part II - recommendations.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2021Article
- Local Immunomodulatory Strategies to Prevent Allo-Rejection in Transplantation of Insulin-Producing Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- Identification and characterisation of tertiary lymphoid organs in human type 1 diabetes.Diabetologia · 2021Article
- Evaluating the Prognostic Value of Islet Autoantibody Monitoring in Islet Transplant Recipients with Long-Standing Type 1 Diabetes Mellitus.Journal of clinical medicine · 2021Article
- Immunological Monitoring in Beta Cell Replacement: Towards a Pathophysiology-Guided Implementation of Biomarkers.Current diabetes reports · 2021Review
48 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveTo investigate if recurrent autoimmunity explained hyperglycemia and C-peptide loss in three immunosuppressed simultaneous pancreas-kidney (SPK) transplant recipients. RESEARCH DESIGN AND
methodsWe monitored autoantibodies and autoreactive T-cells (using tetramers) and performed biopsy. The function of autoreactive T-cells was studied with in vitro and in vivo assays.
resultsAutoantibodies were present pretransplant and persisted on follow-up in one patient. They appeared years after transplantation but before the development of hyperglycemia in the remaining patients. Pancreas transplant biopsies were taken within approximately 1 year from hyperglycemia recurrence and revealed beta-cell loss and insulitis. We studied autoreactive T-cells from the time of biopsy and repeatedly demonstrated their presence on further follow-up, together with autoantibodies. Treatment with T-cell-directed therapies (thymoglobulin and daclizumab, all patients), alone or with the addition of B-cell-directed therapy (rituximab, two patients), nonspecifically depleted T-cells and was associated with C-peptide secretion for >1 year. Autoreactive T-cells with the same autoantigen specificity and conserved T-cell receptor later reappeared with further C-peptide loss over the next 2 years. Purified autoreactive CD4 T-cells from two patients were cotransplanted with HLA-mismatched human islets into immunodeficient mice. Grafts showed beta-cell loss in mice receiving autoreactive T-cells but not control T-cells.
conclusionsWe demonstrate the cardinal features of recurrent autoimmunity in three such patients, including the reappearance of CD4 T-cells capable of mediating beta-cell destruction. Markers of autoimmunity can help diagnose this underappreciated cause of graft loss. Immune monitoring during therapy showed that autoimmunity was not resolved by the immunosuppressive agents used.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.