Alloantibody and Autoantibody Monitoring Predicts Islet Transplantation Outcome in Human Type 1 Diabetes

TLDR

Islet transplantation outcomes are limited by rejection and recurrent autoimmunity. The study seeks to evaluate whether precise monitoring of allo‑ and autoantibody changes can enable early detection and treatment of immune events that compromise graft survival. The authors measured baseline and post‑transplant titers of GAD, IA‑2, ZnT8, and donor‑specific alloantibodies in 59 consecutive islet transplant recipients. Post‑transplant increases in allo‑ or autoantibodies occurred in 66 % of patients, were associated with lower graft survival, HLA‑DR mismatches, ATG induction, high PRA, and rapamycin protection, and thus serve as prognostic markers for poorer outcomes.

Abstract

Long-term clinical outcome of islet transplantation is hampered by the rejection and recurrence of autoimmunity. Accurate monitoring may allow for early detection and treatment of these potentially compromising immune events. Islet transplant outcome was analyzed in 59 consecutive pancreatic islet recipients in whom baseline and de novo posttransplant autoantibodies (GAD antibody, insulinoma-associated protein 2 antigen, zinc transporter type 8 antigen) and donor-specific alloantibodies (DSA) were quantified. Thirty-nine recipients (66%) showed DSA or autoantibody increases (de novo expression or titer increase) after islet transplantation. Recipients who had a posttransplant antibody increase showed similar initial performance but significantly lower graft survival than patients without an increase (islet autoantibodies P < 0.001, DSA P < 0.001). Posttransplant DSA or autoantibody increases were associated with HLA-DR mismatches (P = 0.008), induction with antithymocyte globulin (P = 0.0001), and pretransplant panel reactive alloantibody >15% in either class I or class II (P = 0.024) as independent risk factors and with rapamycin as protective (P = 0.006) against antibody increases. DSA or autoantibody increases after islet transplantation are important prognostic markers, and their identification could potentially lead to improved islet cell transplant outcomes.