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Drug-Induced Autoimmunity
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Robert L. Rubin, Anke Kretz-Rommel
Long-term therapy with some drugs is associated with development of hemolytic anemia due to antibodies bound to red blood cells (RBC) in vivo (direct Coombs test positivity). In the penicillin-type, antibody to the drug binds to RBC as a result of adsorption of the drug or its metabolite to the RBC membrane. In the methyldopa-type, the drug is not required for (and does not effect) antibody binding, and anti-RBC antibodies typically have specificity for rhesus locus or other intrinsic RBC antigens. These antibodies rarely produce frank hemolytic anemia, possibly because their isotype or low avidity does not support complement fixation. Hemolytic anemia is commonly associated with the stibophen-type of drug-induced antibodies (as is quinidine and quinine) in which immune complexes consisting of the drug or drug metabolite bind to RBC presumably via Fc or complement receptors.
Lupus erythematosus syndrome induced by drugs
Published in Philippe Camus, Edward C Rosenow, Drug-induced and Iatrogenic Respiratory Disease, 2010
Even more diagnostically confounding is the development of only haemolytic anaemia after long-term therapy with certain drugs. Some drugs associated with DIA or DIL (methyldopa, L-dopa, procainamide, chlorpromazine and streptomycin) can induce autoantibodies specific for rhesus locus or other intrinsic red blood cell (RBC) antigens (Coombs’ test positive) and occasionally haemolytic anaemia.10 These autoantibodies, unlike the penicillin-type or the stibophen-type of anti-RBC antibodies, behave like the ANA associated with DIA and DIL in that the likelihood for autoantibody appearance is time-and drug-dose-dependent, but the drug is not required for antibody binding to its target antigen. While there is generally no correlation between positive Coombs’ test and ANA, these autoantibodies coexist in some patients.11,12 Drug-induced anti-RBC antibodies of the methyldopa type are also of historical relevance to DIL because, despite the drug-independence of anti-RBC binding, a drug-altered RBC model is commonly invoked10 as the underlying mechanism and also incorrectly used as a paradigm for the origin of autoantibodies associated with DIA and DIL (see the later section, ‘Investigations into mechanisms’).
Hemolysis during short-term mechanical circulatory support: from pathophysiology to diagnosis and treatment
Published in Expert Review of Medical Devices, 2022
Tim Balthazar, Johan Bennett, Tom Adriaenssens
The direct antiglobulin test (DAT) or direct Coombs test is used to detect antibodies or complement factors in RBCs of patients. It is used for diagnosing autoimmune hemolytic anemia (AIHA), where the test shows positivity with anti-IgG and anti-C3d. In case of hemolysis, AIHA should always be excluded with a DAT. In cases of mechanical hemolysis, the DAT is negative (11).