We investigated the mechanism of @entity5714 detected in a repeated-dose @entity137 study using @entity5434 that were treated with a humanized antibody drug. This drug was an IgG1 monoclonal antibody (MoAb) that binds to the @entity1 @entity17406 .24 antigen named anti- @entity17406 .24 MoAb. The presence of the @entity17406 .24 antigen on the erythrocyte membranes and the erythrocyte agglutination following the addition of anti- @entity17406 .24 MoAb was examined. In addition, an indirect Coombs' test, a hemolysis assay and the measurement of anti-single stranded-DNA antibodies were performed using test animal serum or plasma. The specific binding of @entity2823 - and 125I-labeled anti- @entity17406 .24 MoAb to the erythrocyte membrane was not observed. @entity17406 .24 antigen was not identified on the erythrocyte membranes. However, a high concentration (more than 713 microg/mL) of anti- @entity17406 .24 MoAb hemagglutinated the erythrocyte suspensions. The cause of this agglutination was unclear, but it is assumed that the non-specific binding and/or adhesion caused the direct agglutination. In the examination using test serum from the anemic monkeys, a positive reaction in the indirect Coombs' test was noted. Moreover, in these Coombs' test-positive animals, the production of anti-single stranded-DNA antibodies was sequentially increased. In the female monkey sacrificed in extremis due to severe @entity417 , an in vitro hemolytic reaction was detected attributable to complement activation. From these results, the @entity5714 detected in the repeated-dose @entity137 study was diagnosed as a drug-induced @entity5506 ( @entity5506 ) and the primary cause was assumed to be production of IgG class anti-erythrocyte autoantibodies.

Investigation of the mechanism of drug-induced @entity5506 in XXXX elicited by a repeated-dose of a humanized monoclonal antibody drug.

@entity1 :: ('9606', 'Species') :: ['human'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity417 :: ('MESH:D000740', 'Disease') :: ['anemia'] @entity5434 :: ('9541', 'Species') :: ['cynomolgus monkeys'] @entity2823 :: ('MESH:D016650', 'Chemical') :: ['FITC'] @entity5506 :: ('MESH:D000744', 'Disease') :: ['autoimmune hemolytic anemia', 'AIHA'] @entity17406 :: ('11066', 'Gene') :: ['HM1'] @entity5714 :: ('MESH:D000743', 'Disease') :: ['hemolytic anemia']
@entity5434 :: (9541,Species) :: ['cynomolgus monkeys']
