Studies on levamisole--induced agranulocytosis.
Widespread clinical trials of leavo-tetramisole (levamisole) as an immunopotentiating agent in rheumatoid arthritis, metastatic carcinoma, and immunodeficiency states have been complicated by agranulocytosis (AGC) in 2.5%-13% of patients. Other than a relationship with prolonged high dosage, very little is known regarding the pathogenesis of levamisole-induced AGC. Whereas leukoagglutination was negative, fluorochromatic microgranulocytotoxicity (GCY) tests were positive with serum from 10 of 10 acutely neutropenic patients. The antibody was IgM, reacted with 100% of unrelated granulocytes, but not with T or B lymphocytes. Some sera also reacted with monocytes and the myeloid cell line, K-562. Tests for antigen-antibody complexes or cold autoantibodies were negative. Although clinical evidence strongly suggests a haptene (drug) mechanism, in vitro mixing experiments were also negative. An alternative choice parallels the model of aldomet-induced Coombs'-positive hemolytic anemia. Finally, GCY first became positive 2-3 mo prior to the onset of AGC on two patients, suggesting the possibility of identifying those at risk well before the onset of neutropenia.
D000380:Agranulocytosis / Q000139:chemically induced / Q000276:immunology*; D000906:Antibodies / Q000276:immunology*; D000936:Antigen-Antibody Complex; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D001323:Autoantibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001943:Breast Neoplasms / Q000188:drug therapy; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D006801:Humans; D007518:Isoantibodies / Q000276:immunology; D007978:Levamisole / Q000009:adverse effects* / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology
D000906:Antibodies; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D007518:Isoantibodies; D007978:Levamisole