Chapter 24 - Recurrence of type 1 diabetes following simultaneous pancreas-kidney transplantation

Abstract

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, 5–20years after transplantation due to T1D recurrence (T1DR). Over the last two decades, we have assessed autoimmunity in our patients, evaluating T1D-associated autoantibodies (GAD65, IA2, and ZnT8), autoreactive T cells against islet antigens, and pancreas transplant biopsies. Most patients with T1DR demonstrate seroconversion for multiple autoantibodies. Autoreactive memory T cells have been identified in their peripheral blood, pancreas transplant, and peripancreas transplant tissues. Biopsies generally exhibit insulitis, the typical lesion of T1D, affecting pancreatic islets in the pancreas transplant. In addition to membrane surface 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.