Immune Regulation and Graft Survival in Kidney Transplant Recipients Are Both Enhanced by Human Leukocyte Antigen Matching

Abstract

We hypothesized that donor/recipient sharing of the human leukocyte antigen (HLA) involved in allopeptide presentation to the T regulatory cell increases the incidence of immune regulation, thus contributing to long-term graft survival. Peripheral blood mononuclear cells (PBMC) were obtained from 40 living related donor (LRD) and 31 cadaver renal transplant recipients. The trans vivo delayed type hypersensitivity (DTH) assay was used to assign patients to regulator, non-regulator, and sensitized categories. In a large cohort (n = 1934 patients), primary graft survival and rejection episodes were analyzed using a log rank test for comparison with the DTH results. The highest incidence of regulated anti-donor DTH was observed in the LRD HLA-identical group (6/6; 100%) followed by the LRD HLA 1 haplotype matched group (18/27; 67%). Within the cadaver population, two DR-matched recipients had a higher frequency of regulated anti-donor DTH (6/11; 55%) than 1 & 0 DR-matched recipients (3/18; 17%). In a multivariate model, matching for HLA-DR alone, or for DR plus DQ was significantly (p = 0.045, p = 0.041) correlated with DTH regulation. The better HLA-matched groups showed the highest incidence of DTH regulation and, in a larger retrospective analysis, displayed better graft survival and freedom from acute rejection (p < 0.0001). HLA matching, and HLA-DR matching in particular, correlates with the incidence of immune regulation after kidney transplantation.