On the mechanisms of sensitization and attachment of antibodies to RBC in drug-induced immune hemolytic anemia.
The mechanisms of sensitization and attachment of drug-dependent antibodies to RBC in drug-induced immune hemolytic anemias are largely speculative. Nomifensine has been incriminated in causing immune hemolysis in a large number of patients. The hemolysis was usually of the so-called immune complex type, less commonly of the autoimmune type, and more surprisingly, few patients had developed both types of hemolysis. To determine whether nomifensine (metabolite)-dependent antibodies (ndab) exhibit specificity for antigenic structures of RBC membranes, 30 ndab were tested against large panels of RBC with common and rare antigens. We found that only 14 out of 30 ndab were invariably reactive with all cells tested. Nine antibodies were, similar to the majority of idiopathic or drug-induced autoantibodies, not or only weakly reactive with Rhnull RBC. Three antibodies did not react with cord RBC and could be inhibited by soluble I antigen. The remaining four antibodies gave inhomogeneous reaction patterns or were even negative with selected RBC; their specificity could not be identified. On a Scatchard plot analysis of one ndab, a maximum of 173,000 drug-dependent antibodies of the IgG class can specifically bind per RBC in the presence of the drug. Although nomifensine and its metabolites do not attach tightly onto RBC, our results clearly indicate that RBC do not act as "innocent bystanders," but rather serve as a surface for a loose attachment of drugs that possibly cause a subtle structural change in the cell antigens and, by this means, allow in vivo sensitization; and a specific binding of the resultant antibodies. This concept would explain why these antibodies can be directed against drug-cell complexes, against cell antigens alone (autoantibodies), or against both in the same patient.
D000744:Anemia, Hemolytic, Autoimmune / Q000139:chemically induced / Q000276:immunology*; D000918:Antibody Specificity; D000954:Antigens, Surface / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D002392:Catechin / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology*; D006801:Humans; D007048:I Blood-Group System; D008750:Methyldopa / Q000276:immunology; D009627:Nomifensine / Q000276:immunology; D012204:Rh-Hr Blood-Group System / Q000276:immunology
D000954:Antigens, Surface; D001323:Autoantibodies; D007048:I Blood-Group System; D012204:Rh-Hr Blood-Group System; D009627:Nomifensine; D008750:Methyldopa; D002392:Catechin