HLA sensitization in islet transplantation

Abstract

Islet transplantation is an emerging therapy for poorly controlled type 1 diabetes. Currently, islets isolated from multiple donors not HLA-matched to recipients are usually required to achieve insulin-independence. Subsequent HLA sensitization is common following a reduction or discontinuation of immunosuppressive drugs and may be responsible for deterioration in islet graft function. Based on the evidence available to date concerning HLA sensitization in islet transplant recipients, we recommend that future islet transplantation protocols consider the following: (1) minimizing the number of islet donors by, for example, infusing high quality islet preparations of sufficient yield from a single donor rather than pooling islet preparations from multiple donors since a greater number of HLA class I mismatches appears to be associated with increased risk for sensitization; (2) ensuring negative cross-matching of donor lymphocytes and recipient sera by testing prior to islet infusions; (3) avoiding donor-recipient antigen mismatches when an identifiable alloantibody is present pre-transplant (i.e., in the case of a positive PRA pretransplant) but excluding potential recipients who are highly sensitized (e.g., have a PRA > or = 20%); and (4) performing an assessment for HLA sensitization using a sensitive flow cytometric method for alloantibody detection any time there is a reduction in immunosuppressant drug levels or worsening of metabolic control.