IMPROVED ALLOGRAFT SURVIVAL OF STRONG IMMUNE RESPONDER-HIGH RISK RECIPIENTS WITH ADJUVANT ANTITHYMOCYTE GLOBULIN THERAPY

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Abstract
The pretransplant cellular immune responsiveness of 90 renal failure patients was correlated with subsequent allograft survival. Patients were subdivided on two bases: whether the pretransplant immune parameter values were above (strong responder) or below (weak responder) the group median, and whether they were responsive or anergic to recall skin test antigens. In a group of 72 cadaveric renal allograft recipients, treated with only Imuran and prednisone, the overall 1-year graft survival was 48%. Pretransplant immunocompetence correlated with graft survival: factors predicting longer allograft survival (P < 0.01) included: percentage of active T rosette-forming cells (A-T RFCs) < 36.5%, anergy to microbial skin test (ST) antigens, in vitro spontaneous blastogenesis (SB) < 14,600 cpm, and response to a panel of five donors in mixed lymphocyte culture (PMLC) < 28,000 cpm. In the two groups, weak and strong responders, the 1-year graft survival rates differed: 63% versus 32% when segregated by the A-T RFC parameter, 63% versus 33% for ST, 57% versus 36% for SB, and 63% versus 35% for PMLC. There were no significant differences in the number of HLA mismatches between the two groups. An additional group of 18 patients was treated with adjuvant immunosuppressive therapy by prophylactic administration of antithymocyte globulin (ATG; Upjohn Co.). Strong, but not weak, responders treated with ATG displayed a significantly improved (P < 0.01) 1-year graft survival over that of the untreated group. Thus, pretransplant immunological assessment may guide the selection of adjuvant immunosuppressive therapy to improve renal allograft survival in strong immune responders at high risk of rejection.