Thompson J S, Herbick J M, Klassen L W, Severson C D, Overlin V L, Blaschke J W, Silverman M A, Vogel C L
Blood. 1980 Sep;56(3):388-96.
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.
左旋四咪唑作为免疫增强剂在类风湿性关节炎、转移性癌和免疫缺陷状态中的广泛临床试验因2.5%-13%的患者出现粒细胞缺乏症（AGC）而变得复杂。除了与长期高剂量有关外，关于左旋四咪唑诱导AGC的发病机制知之甚少。虽然白细胞凝集试验为阴性，但10例急性中性粒细胞减少患者的血清荧光微粒细胞毒性（GCY）试验均为阳性。抗体为IgM，与100%的无关粒细胞反应，但不与T或B淋巴细胞反应。一些血清也与单核细胞和髓系细胞系K-562反应。抗原-抗体复合物或冷自身抗体检测均为阴性。尽管临床证据强烈提示半抗原（药物）机制，但体外混合实验也为阴性。另一种选择类似于阿糖腺苷诱导的库姆斯阳性溶血性贫血模型。最后，两名患者在AGC发作前2-3个月GCY首次呈阳性，提示在中性粒细胞减少症发作前很久就有可能识别出有风险的患者。
