IDENTIFICATION OF PATIENTS AT HIGH-RISK OF GRAFT LOSS BY PRETRANSPLANT AND POSTTRANSPLANT MONITORING OF ANTI-HLA CLASS-I IGG ANTIBODIES BY ENZYME-LINKED-IMMUNOSORBENT-ASSAY

Identification of risk factors influencing graft survival may lead to the development of models to predict graft outcome, Such models may pr ovide guidance for immunosuppressive therapy, measure posttransplantat ion outcome, and eventually improve graft survival in high-risk patien ts. A major risk factor influencing graft survival is allosensitizatio n. However, due to the lack of standardization of lymphocytotoxicity a ssays, the detection of alloantibodies utilizing this current methodol ogy may not correlate with posttransplant events. Recently, a novel st andardized enzyme-linked immunosorbent assay (ELISA) for the detection of anti-HLA class I IgG antibodies was developed. To evaluate the pre dictive value of this diagnostic test, a retrospective analysis of 124 renal allograft recipients with an Is-month follow-up time was perfor med, A highly significant (P=0.01) correlation between pretransplant E LISA panel reactive antibody (PRA) results and graft loss was observed . Patients with pretransplant ELISA PRA of >10% had a three times high er risk of graft loss compared with patients who tested negative, No s uch correlation was observed with complement-dependent cytotoxicity re sults independent of the reduction of IgM antibodies with dithiothreit ol. Similarly, a highly significant correlation of ELISA results with the occurrence of early graft dysfunction was observed, Almost all pat ients (88%) with a pretransplant ELISA PRA of >50% required posttransp lant dialysis, compared with 45% of patients with a pretransplant ELIS A PRA of 10-50% and 27% of patients with a pretransplant ELISA PRA of <10%. No such difference was observed with complement-dependent cytoto xicity %PRA values. Analysis of posttransplant specimens by ELISA demo nstrated a strong correlation of assay results with graft rejection an d graft dysfunction. In summary, these results suggest that detection of anti-HLA class I antibodies by ELISA identifies patients at high ri sk for graft loss, No other single risk factor of such magnitude has b een identified so far.