"Anti-idiotypic" antibodies to HLA in transiently sensitized DST patients.

To test the hypothesis whether "anti-idiotypic" antibodies (Ab2) were involved in the loss of sensitization following donor-specific blood transfusions (DST), we investigated nine potential kidney graft recipients who became transiently sensitized after DST. Inhibiting "anti-idiotypic" activity of post-DST sera was determined using a complement-dependent cytotoxicity inhibition assay. The follow-up after DST ranged from 9 to 66 months. The nine patients developed 12 different anti-HLA antibodies (Ab1). Inhibiting post-DST serum activity was found in relation to four of them, while enhancement of cell killing caused by post-DST sera was observed in relation to six anti-HLA antibodies. In two patients presenting with more than one anti-HLA antibody inhibition was found with only one of the antibodies, indicating that the blocking of Ab1 was specific for the respective antibody. Enhancement was associated with a significantly prolonged sensitization of the patients. On the average, 5.7 +/- 5.0 months were necessary before "anti-idiotypic" activity was developed after the loss of sensitization, whereas enhancement was found immediately thereafter. Testing by flow cytometry indicated that enhancing sera still contained subthreshold levels of Ab1. Our results indicate that DST can induce the development of "anti-idiotypic" antibodies following a short period of sensitization. This finding provides further evidence that anti-idiotypic antibodies might be relevant factors in the eventual disappearance of sensitization to HLA antigens.