Characterization of antiidiotypic antibodies to donor HLA that develop after liver transplantation

Several studies have reported the development of antiidiotypic antibodies to anti-HLA alloantibodies in renal allograft transplant recipients, 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 circulating soluble donor HLA antigens, sera obtained from liver recipients, both pre- and posttransplantation, were analyzed for cytotoxicity inhibitory activity against alloantisera to mismatched donor HLA antigens. Prior to cytotoxicity inhibition assays, sera were absorbed with W6/32 coupled sepharose in order to remove circulating HLA antigens. Antiidiotypic antibodies to anti-HLA class I antibodies were detected in the sera of 7 out of 9 recipients, and antibodies to anti-HLA class II were found in the sera of 4 out of 7 recipients. Antiidiotypic antibodies were detected only during the immediate posttransplantation period. The specific inhibitory activity noted against both HLA class I and II mismatches showed no detectable preference for either HLA class or locus. Furthermore, the antiidiotypic antibodies to HLA developed in liver recipients also inhibited alloantisera to HLA-specific public epitopes or crossreactive groups (CREGS). Cytotoxicity inhibition by posttransplant 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 ability to inhibit cytotoxicity by donor-specific alloantisera. Thus these studies indicate that the development of antiidiotypic antibodies to anti-HLA is common during the immediate period following liver transplantation, even though circulating donor HLA antigens are present. The presence of circulating donor HLA antigens and the development of antiidiotypic antibodies to donor-specific anti-HLA during this period may be important for the successful adaptation of mismatched liver allografts.