ASSOCIATION OF Fc RECEPTOR-BLOCKING ANTIBODIES AND HUMAN RENAL TRANSPLANT SURVIVAL

Abstract

Antibodies to B lymphocytes were monitored in previously transfused recipients of cadaver donor renal allografts. Of 43 patients investigated before transplantation, in 20 of these the development of antibodies post-transplant was also studied. B lymphocyte antibodies were detected by lymphocytotoxicity and EA [erythrocyte-antibody] inhibition (EAI) against donor, normal panel and leukemic B lymphocytes (CLL). The latter assay detects Fc receptor-blocking antibodies. Of those with pretransplant EAi against donor lymphocytes 85% (11 of 13) had grafts which survived for 1 yr compared with only 30% (6 of 20) of those without such antibodies (P < 0.01). Similarly 74% (14 of 19) of those with, but only 38% (9 of 24) of those without, antinormal panel EAI had grafts which survived for 1 yr (P < 0.05). Seventy-seven percent (17 of 22) of those with EAI against the CLL panel, but only 29% (6 of 21) of those without, had grafts surviving for 1 yr (P < 0.01). When EAI developed only post-transplant against any type of target lymohocyte, the graft had invariably failed by 1 yr. If EAI had also occurred pretransplant, the favorable graft outcome associated with that persisted. EAI against both sets of panel lymphocytes was not directed against lymphocytes bearing any particular HLA-DR specificity, suggesting that these EA-inhibiting antibodies were not directed against classically defined HLR-DR antigens. The sera which demonstrated EAI were not necessarily the same sera which showed lymphocytotoxic activity, indicating the heterogeneous nature of B lymphocyte antibodies. Lymphocytotoxic antibodies were detected relatively infrequently pre- and post-transplant and no statistically significant correlation could be made without allograft survival. The development of EAI post-transplant correlates with poor renal allograft survival and shows that pretransplant Fc receptor-blocking antibodies are associated with improved graft survival.