A new bioinformatics analysis can reveal intestinal infection as a cause of graft rejection in islet xenotransplantation in non-human primate. (TRAN1P.940)

Abstract

Abstract Pancreatic islet transplantation is one of the most attractive treatment modality for select type 1 diabetes patients suffering from frequent hypoglycemia unawareness. However, because of the shortage of human donor organs, xenotransplantation is becoming more highlighted. Under this circumstance, we have recently achieved reproducible and consistent survivals of adult porcine islet for more than 180 days in the liver of five diabetic monkeys under immunosuppression regimen base on anti-CD154. Interestingly, among five monkeys, one has exhibited graft failure after having experienced severe intestinal infections. Because the porcine islets were exposed to direct blood flow from the intestine, intestinal infection would exert detrimental effect on porcine islets. To test this hypothesis, we performed RNA-seq with peripheral blood from graft maintaining monkey or rejecting monkey after intestinal infections. By using novel bioinformatics tool called Time-series RNA-seq analysis package, we demonstrated highly relevant activated immunologic pathway in graft rejecting monkey, but not in well maintaining monkey. Consistent with this notion, we further confirmed that porcine islets were indeed rejected by CD8+ T cells by immunohistochemistry. Taken together, we for the first time showed that a new bioinformatics analysis using peripheral blood RNA-seq data can pinpoint intestinal infection as a cause of graft rejection in intraportal islet xenotransplantation.