Natural antibodies against the immunoglobulin F(ab′)2fragment cause elimination of antigens recognized by the F(ab′)2from the circulation

摘要

AbstractA humanized monoclonal IgG1 antibody, designated hC4G1, recognizes the fibrinogen receptor glycoprotein (GP)IIb/IIIa on platelets and inhibits platelet aggregation. When the F(ab′)2fragment of hC4G1 (F(ab′)2hC4G1) was administered to cynomolgus monkeys, all the monkeys showed inhibition of platelet aggregationex vivo. Unexpectedly, a significant decrease in platelet count was observed in 5 of 18 monkeys. Antibodies against F(ab′)2hC4G1 were detected in the plasma of these monkeys by ELISA. Antibody activity in the plasma of these monkeys was significantly correlated with the intensity of platelet decrease (r= 0.84). The natural monkey antibodies to F(ab′)2hC4G1 were directed against the C‐terminal region of F(ab′)2fragment common to all human and humanized IgG antibodies. Natural homo‐reactive antibodies were also detected in human plasma from 15 of 40 healthy volunteers. Specificity was closely similar to that of the monkey antibodies. Affinity‐purified human homo‐reactive antibodies enhanced phagocytosis of platelets treated with the F(ab′)2hC4G1. Monkey plasma with high homo‐reactive antibody activity was confirmed to decrease platelet count when administered together with F(ab′)2hC4G1 to a monkey with low antibody activity. These results suggest that F(ab′)2of humanized and human antibodies causes elimination of the corresponding antigens from the circulation by