IMMUNOGLOBULIN-G LYMPHOCYTOTOXIC ANTIBODIES IN CLINICAL LIVER-TRANSPLANTATION - STUDIES TOWARD FURTHER DEFINING THEIR SIGNIFICANCE

Twenty-two consecutive liver allograft recipients, who tested positive for immunoglobulin G (IgG) lymphocytotoxicity were subjected to pretr ansplantion and posttransplantation immunologic monitoring of antidono r IgG lymphocytotoxic antibody titers, total hemolytic complement acti vity (CH100), circulating immune complexes (CIC), and platelet counts in an effort to improve our understanding of the preformed antibody st ate in clinical hepatic transplantation. Ten contemporaneous liver tra nsplant recipients whose crossmatch results were negative and who expe rienced severe hepatocellular damage early after transplantation were included as controls. Crossmatch test results were negative 1 day afte r transplantation and during the 1 month follow-up remained negative i n 14 of 22 (64%) sensitized recipients, most of whom had relatively lo w (less than or equal to 1:16) antidonor IgG antibody titers before tr ansplantation. After transplantation, this group and the control group experienced no thrombocytopenia, no increase of CIC and a gradual inc rease in CH100 activity that reached normal, levels within 1 week. A s trong negative correlation between prothrombin time (PT) and CH100 act ivity in these groups of patients suggested that changes in CH100 acti vity (P <.0005) were tightly linked to Liver synthetic function. In co ntrast, the crossmatch test results remained positive after transplant ation in 8 of 22 (36%) sensitized recipients, all of whom had relative ly high (>1:32 to 1024) pretransplantation titers of anti-donor IgG an tibodies. After transplantation these patients developed a syndrome th at was characterized by decreased CH100 activity and increased CIC com pared with pretransplantation levels and refractory thrombocytopenia t hat was associated with a 50% allograft failure rate because of biopsy -proven humoral and acute (cellular) rejection. Moreover, the lack of a strong negative correlation between PT and CH100 activity (P =.1) in this group of patients suggested that the hypocomplementemia was not tightly Linked to liver synthetic function. Before transplantation, de termination of anti-donor antibody class (IgG) and titer alone showed a strong negative predictive value (100%) but less than optimal positi ve predictive value (67%) for identifying patients who experienced the posttransplantation syndrome described above. Therefore, evaluation o f platelet counts, CH100 activity, CIC, persistence of anti-donor anti bodies and results of a Liver biopsy performed after transplantation a ssisted in identifying sensitized liver allograft recipients who suffe red the adverse consequences of the preformed antibody state.