Sharing cross-reactive groups of MHC class I improves long-term graft survival

Background. Renal transplant loss from chronic rejection remains substantia l. To increase our understanding of this syndrome, we identified risk facto rs predicting late graft loss, with a special emphasis on the impact of hum an lymphocyte antigen (HLA) matching. Methods. We studied all 654 cadaveric kidney transplants performed in our c enter between 1983 and 1996 that had survived for more than sir months. Eig hty-two transplants, lost because of chronic rejection, were used as the ou tcome variable. The influence of HLA mismatches and shares an longterm graf t survival was evaluated at the level of private antigens and cross-reactiv e groups (CREG) of multiple histocompatibility complex (MHC) class I. HLA a nd other recipient, donors and transplant parameters were studied using uni variate and multivariate Cox regression analysis. Results. The cohort had a mean number of 1.9 HLA mismatches. Because of the homozygosity of HLA antigens, HLA mismatches were not reciprocal to shares . CREG and HLA-A-B mismatches had a relative risk for graft loss of 1.19 (9 5% CI, 0.97 to 1.45) and 1.05 (0.84 to 1.32) per mismatch. In contrast, the relative risk per shared CREG and broad HLA-A-B antigen was 0.76 (0.63 to 0.92) and 0.79 (0.61 to 1.03). Multivariate analysis revealed that individu als sharing less than four CREGs had a relative risk of 2.13 (1.29 to 3.75) for late graft loss. Other independent predictors were a recipient age of less than 50 years, relative risk 1.95 (1.02 to 3.71); a donor age of more than 50 years, relative risk 1.68 (1.01 to 2.80); acute rejection (vascular vs. no rejection), relative risk 3.52 (1.72 to 7.18); proteinuria (dipstic k > 1+ vs. negative), relative risk 2.86 (1.29 to 6.35); and a serum creati nine concentration of more than 150 mu mol/liter at six months, relative ri sk 3.41 (1.96 to 5.94). Conclusion. We identified several coexisting recipient-, donor-, and transp lant-related risk factors for graft loss from chronic rejection. In this we ll-matched group of renal transplants, HLA mismatches and shares had a nonr eciprocal relationship. Sharing of HLA antigens, especially CREG of MHC cla ss I? was associated with improved long-term survival.