P068 Transplant tolerance in heart transplant recipients: It is all in the genes

Abstract

Aim The “holy grail” of transplantation is donor specific tolerance in the absence of immunosuppression. There are no cases reported of survival without immunosuppression in heart transplant recipients. This prospective study identifies a group of heart transplant recipients who have developed tolerance to the transplanted organ. We hypothesize that these recipients were pre-disposed to survival without immunosuppression. Identification of a gene signature in these recipients could help understand the mechanism of development of transplant tolerance in heart transplant recipients. Methods We identified 8 cardiac transplant patients with a history of at least 7 days without immunosuppression (TOL group). Comparator groups included (i) 120 days post-transplant patients without rejection (11 pts), (ii) 5 years post-transplant patients with normal graft function (15 pts) (iii) patients with acute cellular rejection ISHLT 2R or greater (5 pts). Blood samples were obtained and total RNA extracted from PBMCs was reverse transcribed to cDNA. The cDNA was overlaid onto 96-well PCR plates containing customized gene-specific PCR primer pairs for Treg regulation genes and analyzed using quantitative Real Time PCR. Results We observed 15 genes which were differentially expressed between the TOL and rejector (REJX) groups. As shown in Table 1, genes that play an important role in the regulation of Tregs that is central to the development of a potentially tolerant state showed a significant higher expression in the TOL group as compared to REJX group. Conclusions This is the first report of a group of heart transplant patients surviving more than transiently without immunosuppression. The existence of these patients and the documented gene expression differences supports further research into mechanisms and potential ways to identify the development of tolerance in heart transplant patients. Download : Download high-res image (89KB) Download : Download full-size image