CHARACTERIZATION OF ANTIIDIOTYPIC ANTIBODIES TO DONOR HLA THAT DEVELOP AFTER LIVER-TRANSPLANTATION

Several studies have reported the development of antiidiotypic antibod ies to anti-HLA alloantibodies in renal allograft transplant recipient s, postulating their potential beneficial role in allograft survival. In order to evaluate the role of anti-HLA antiidiotypic antibodies in human liver transplant recipients and to differentiate them from circu lating soluble donor HLA antigens, sera obtained from liver recipients , both pre- and post-transplantation, were analyzed for cytotoxicity i nhibitory activity against alloantisera to mismatched donor HLA antige ns. Prior to cytotoxicity inhibition assays, sera were absorbed with W 6/32 coupled sepharose in order to remove circulating HLA antigens. An tiidiotypic antibodies to anti-HLA class I antibodies were detected in the sera of 7 out of 9 recipients, and antibodies to anti-HLA class I I were found in the sera of 4 out of 7 recipients. Antiidiotypic antib odies were detected only during the immediated posttransplantation per iod. The specific inhibitory activity noted against both HLA class I a nd II mismatches showed no detectable preference for either HLA class or locus. Furthermore, the antiidiotypic antibodies to HLA developed i n liver recipients also inhibited alloantisera to HLA-specific public epitopes or crossreactive groups (CREGS). Cytotoxicity inhibition by p osttransplant sera was not mediated by circulating HLA antigens since absorption of the sera with monoclonal anti-HLA framework reagents did not change the specific inhibition of the alloantisera. In addition, the immunoglobulin fraction of the posttransplant sera retained its ab ility to inhibit cytotoxicity by donor-specific alloantisera. Thus the se studies indicate that the development of antiidiotypic antibodies t o anti-HLA is common during the immediate period following liver trans plantation, even though circulating donor HLA antigens are present. Th e presence of circulating donor HLA antigens and the development of an tiidiotypic antibodies to donor-specific anti-HLA during this period m ay be important for the successful adaptation of mismatched liver allo grafts.