An increase in the level of anti-Gal IgM is associated with an early graft failure in intraportal porcine islet xenotransplantation (TRAN1P.935)

Abstract

Abstract In order to develop laboratory tests to predict graft outcome in porcine islet transplantation (ITx), we investigated the association between anti-Gal antibody responses and the graft failure in NHP recipients after porcine ITx. Total 35 naïve diabetic NHP recipients were intraportally administered with adult porcine islets and then graft function was monitored. Early graft failure (EGF) was defined as returning to diabetic state within a month after ITx. Among the recipients, 7 and 28 received induction immunosuppression (IS) without and with CD40 pathway blockade, respectively: 19, anti-CD154 and 9, anti-CD40. The levels of anti-Gal IgG and IgM in the recipients on the day 0 (0 d) and on the day 7 (7 d) of ITx were quantitatively measured by in-house ELISA. Whereas an increase in the level of anti-Gal IgG after ITx was suppressed by the use of either anti-CD154 or anti-CD40, a response of anti-Gal IgM was suppressed by anti-CD154, not by anti-CD40. The anti-Gal antibody ratio of 7 d/0 d was significantly higher in the recipients with EGF than in those without EGF (IgG ratio, 1.54 vs 0.75, P=0.0025; and IgM ratio, 1.48 vs 0.87 P=0.0035). An increase in the level of anti-Gal IgM on the day 7 of ITx is significantly associated with EGF in the recipients with porcine ITx regardless of use of CD40 pathway blockade, suggesting that an early response of anti-Gal IgM may reflect the innate immune responses which account for killing of porcine islets in early period of porcine ITx.