Human Rh D Monoclonal Antibodies (BRAD-3 and BRAD-5) Cause Accelerated Clearance of Rh D+ Red Blood Cells and Suppression of Rh D Immunization in Rh D- Volunteers

摘要: The use of prophylactic anti-D to prevent Rh D immunization in D- women and subsequent hemolytic disease D+ infants is widespread, but has led shortages the Ig. With aim substituting monoclonal for prophylaxis, we have compared abilities polyclonal clear red blood cells (RBCs) infused into male volunteers suppress immunization. Two human antibodies (MoAbs), BRAD-3 (IgG3) BRAD-5 (IgG1), produced from stable Epstein-Barr virus-transformed B-lymphoblastoid cell lines, were selected because their proven vitro activity promoting RBC lysis antibody-dependent cell-mediated cytotoxicity assays. clearance was assessed by intravenous injection 3 mL 51chromium-labeled RBCs 27 48 hours after intramuscular or anti-D. Further 3-mL injections unlabeled administered at 6 9 months induce Blood samples taken throughout 12-month period study serologic detection mean half-life (t50%) 7 recipients 300 micrograms (5.9 hours) similar that 8 500 IU (5.0 hours), whereas cleared more slowly some subjects injected with (mean t50% 12.7 1 individual 100 (t50% 41.0 hours). rate both groups correlated amount antibody bound per cell, determined flow cytometry. There no evidence primary having occurred any subject follow-up. Five 24 one two further RBCs, confirming they responders who had been protected initially. Four these (3 BRAD-3, BRAD-5). One received accelerated third unprotected challenge did not seroconvert. This shows MoAbs can immunization, indicates may be suitable replacements presently used prophylaxis newborn.(ABSTRACT TRUNCATED AT 400 WORDS)