Implication of IFNγ Production in Clinical Allogeneic Islet Transplantation in Contrast to Autologous Transplantation.

Abstract

Introduction: We have shown that the autoimmune response to GAD65 peptide is a crucial cause of graft dysfunction in clinical islet transplantation for type 1 diabetes and a significant IFNγ release from CD4+ or CD8+ T cells which corresponded with the autoimmune response. In this study, the serum IFNγ levels in allogeneic islet recipients were assessed, in comparison with autologous recipients. Methods: Six allogeneic and 6 autologous islet recipients were included. Patients in both groups matched in basic characteristics. There was no difference in transplanted islet dose between both groups: 9,393±707 and 7,949±672 IEQ/kg of body weight, respectively (p=0.17). All recipients were administered with both etanercept and anakinra from Day 0 to 10. Autoimmune response was investigated with EpiMax assay after stimulation of peripheral blood mononuclear cells by GAD65 peptide clusters. Cytokine levels were measured using Luminex assay. Results: Significant IFNγ production from both CD4+ and CD8+ T cells was observed at peri-transplant in allogeneic islet recipients (Fig. A). Significant elevation of serum IFNγ levels were also seen immediately after islet infusion in allo-recipients and the elevation were sustained for 7 days (Fig. B). Autologous recipients, however, did not show significant increase in IFNγ levels. Conclusions: Significant difference in serum IFNγ levels was observed between allogeneic and autologous islet recipients even when similar dose of islets were transplanted. Further characterization of IFNγ production may help to determine the role of autoimmune response in clinical islet transplantation.Figure: No Caption available.Figure.: An example of IFNγ production in EpiMax assay in an allogeneic recipient (A) and serum IFNγ levels in islet transplantation (B) are shown.