Chronic graft dysfunction in allogeneic islet cell transplantation

Currently, >70% of recipients of islet cell transplantation achieve insulin independence. However, maintaining insulin independence is difficult due to chronic rejection. In 2005, it was shown that the insulin-free rate 5 years after islet cell transplantation was <10%. This very low long-term insulin-free rate is considered chronic graft dysfunction, which is caused by allosensitization, autoimmune recurrence, and other factors. Recently, several groups demonstrated improved long-term results for islet cell transplantation after introducing a potent induction immunosuppression therapy, supplemental islet cell transplantation, and transplantation of a high quality and quantity of islets. Thus, these interventions might be key factors in overcoming chronic graft dysfunction. In this chapter, we describe the current status of allogeneic islet transplantation for the treatment of type 1 diabetes; the possible causes of chronic graft dysfunction, including late acute rejection, allosensitization, autoimmune recurrence, and nonimmunological factors; and recent strategies to overcome chronic dysfunction, including new immunosuppression protocols, supplemental islet transplantation, the monitoring of islet graft function, immune monitoring, and an anti-inflammatory strategy.