Immune Antibody Monitoring Predicts Outcome in Islet Transplantation

Abstract

With over 40 years of intense collaborative research in the making, has clinical islet transplantation finally come of age? This cellular replacement tool has been tried and tested in over 1,000 patients undergoing various forms of islet transplantation since 2000, and it is becoming increasingly safe, effective, and durable in stabilizing glycemic control, HbA1c, and lowering the risk of secondary complications in refractory type 1 diabetes (1–4). Evanescent rates of insulin independence observed by 3 years in previous protocols were multifactorial in origin, but driven predominantly by an innate and adaptive immunologic response to transplanted cells (5). The good news is that more effective control of inflammation, auto- and alloimmunity with rationally targeted induction, and maintenance therapeutics have recently led to marked improvement in 5-year insulin independence rates exceeding 50% in six independent transplant centers (1,6–8). This milestone places islet transplantation, albeit in highly selected centers, on a par with whole pancreas–alone transplantation, while avoiding surgery and attendant risk (6). While this pace of progress is indeed impressive, major challenges remain, and include 1 ) the current need for intense induction and maintenance immunosuppression; 2 ) limited access and funding for islet processing and transplant facilities; and 3 ) low single-donor engraftment rates in the …