Pretransplant Immune Parameters Associate With Islet Allograft Outcome

Implications for Transplant Strategy?

Extensive and informative immunological assessments of islet transplant recipients have been limited due, in part, to the smaller numbers of patients transplanted compared with solid organ trials. Limitations related to blood volume and the logistical challenges of collecting multiple posttransplant samples for drug levels as well as clinical and metabolic parameters also pose challenges. Several variables affect islet allograft outcome, including allo- and autoimmune responses to transplanted islets, β-cell mass and islet quality, efficacy of the immunosuppressive regimen and its effect on islet function, as well as glycemic control. In fact, much debate has centered on whether or not islet attrition is due to immune-mediated loss, death of overworked cells caused by insufficient mass, and/or diabetogenic effect of various immune intervention agents. In addition, many of these parameters may have differing effects based on the transplanted mass, with marginal mass transplants being more susceptible to immune-mediated or stress-induced loss.

Recently, several studies have demonstrated immunological alterations in islet allograft patients. Posttransplant changes in lymphocytes and lymphocyte subsets were reported to be variable depending on the immune suppression used but have not yet been associated with graft status or specific clinical outcomes (1–4). Higher posttransplant cytotoxic T-cell precursor frequency against donor antigens was associated with poorer outcome at 6 months in recipients treated with sirolimus-based maintenance therapy but not tacrolimus–mycophenolate mofetil (5). In one study, cytokine production in allogeneic mixed lymphocyte reactions (MLRs) was skewed toward …