DETERMINATION OF ANTIIDIOTYPIC ANTIBODIES TO ANTI-HLA IgG FOLLOWING BLOOD TRANSFUSIONS

Abstract

Blood transfusions (BT) administered prior to renal allograft transplantation are known to enhance allograft survival. One proposed mechanism for this effect is through the induction of antiidiotypic antibodies that modify the immune response to subsequently presented graft antigens. In an attempt to determine if antiidiotypic antibodies are generated post-BT, we studied sera from post-BT patients for the presence of antiidiotypic antibodies to anti-HLA class I IgG (i.e., anti-anti-HLA). Anti-HLA antiidiotypes were demonstrated by idiotypespecific inhibition of an enzyme immunoassay (EIA) for anti-HLA antibodies. Using this inhibition technique, test sera from 8 of 16 post-BT patients showed significant inhibition of the anti-HLA target sera (P < 0.05). Sera from normal individuals showed no inhibition of the target sera, and test sera did not inhibit other antigen-antibody systems. Protein A absorption of test sera eliminated the inhibitory effect, suggesting that the antiidiotypic activity was limited to the IgG fraction of the sera. The EIA binding activity of F(ab'')2 fragments of anti-HLA IgG was suppressed by sera from patients post-BT but not by sera from normal volunteers. Studies of serially obtained sera from a post-BT patient showed that anti-HLA antiidiotypic levels fluctuate with time and transfusion status. These studies demonstrate that anti-HLA antiidiotypic antibodies are generated post-BT. Their importance in mediating the known allograft-enhancing effect of pretransplant BT remains to be clarified.