IN VITRO DIAGNOSIS/PROGNOSIS METHOD AND KIT FOR ASSESSMENT OF TOLERANCE IN LIVER TRANSPLANTATION

摘要

In vitro diagnosis/prognosis method and kit, for assessment of tolerance in liver transplantation. The present invention refers to the study of peripheral blood transcriptional patterns from 80 liver transplant recipients and 16 - non-transplanted healthy individuals employing either oligonucleotide microarrays and/or quantitative real-time PCR to design a clinically applicable molecular test. This has resulted in the discovery and validation of several gene signatures comprising a modest number of genes capable of. identifying tolerant and non-tolerant recipients with high accuracy. The marker genes are KLRFl, SLAMF7, NKG7, IL2RB, KLRBl, FANCG, GNPTAB, CLIC3, PSMD14, ALG8, CX3CR1, RGS3, CD9, CD244 and CD160. Multiple peripheral blood lymphocyte subsets contribute to the tolerance-associated transcriptional patterns with NK and ? delta T cells exerting a predominant influence. The invention concludes that transcriptional profiling of peripheral blood can be employed to identify liver transplant recipients who can discontinue immunosuppressive therapy and that innate immune cells are likely to play a major role in the maintenance of operationally tolerance in liver transplantation.