Type 1 Diabetes Recurrence After Simultaneous Pancreas-Kidney Transplantation

Simultaneous pancreas-kidney transplantation (SPKT) is an important option for patients with type 1 diabetes (T1D) and end-stage renal disease. While most SPKT recipients experience long-term euglycemia, about 5% return to insulin therapy, 5–20 years after transplantation due to T1D recurrence (T1DR). Over the last two decades, we have assessed autoimmunity in our patients, evaluating autoantibodies (GAD65, IA2, and ZnT8), autoreactive T cells, and pancreas transplant biopsies. Most patients demonstrate seroconversion for multiple autoantibodies. Autoreactive memory T cells have been identified in the peripheral blood, pancreas transplant, and peri-pancreas transplant tissues. Biopsies generally exhibit insulitis, the typical lesion of T1D, affecting pancreatic islets in the pancreas transplant, and lack of rejection in the pancreas and kidney transplants. In addition to membrane expression of memory markers, we have identified other biomarkers, including CXCR3, on circulating and infiltrating autoreactive memory T cells. We hope that this work will lead to therapeutic intervention in our patients with T1DR, and that this will translate to effective treatment for T1D.