Williams C L, Lennon V A, Momoi M Y, Howard F M
Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905.
Ann N Y Acad Sci. 1987;505:168-79. doi: 10.1111/j.1749-6632.1987.tb51290.x.
The biochemical identities of several antigens to which striational antibodies bind were determined by using serum antibodies and monoclonal antibodies from two patients with myasthenia gravis. The monoclonal antibodies were secreted by EBV-transformed B-lymphocyte clones obtained from thymus and thymoma. Serum and monoclonal antibodies reacted with discrete components of the skeletal muscle sarcomere, giving rise to several different patterns of immunofluorescence staining. Immunoblot analyses and enzyme-linked immunosorbent assays revealed three different antibody specificities: myosin, alpha-actinin, and/or actin. Individual monoclonal StrAb reacted with both muscle and nonmuscle isotypes of actin or myosin. It is noteworthy that contractile proteins (1) are associated with acetylcholine receptors (AChR) in plasma membranes, and (2) are biochemically altered in transformed cells. It is therefore conceivable that the release of neoantigenic AChR-associated contractile proteins from thymic epithelial cells undergoing neoplastic transformation may provide the immunogenic stimulus for production of StrAb. More precise definition of StrAb specificities in individual patients with MG and/or thymoma might provide a basis for diagnostic and/or prognostic classification of these diseases. Furthermore, the monoclonal antibodies will be useful in experimentally testing the potential pathogenicity of StrAb.
利用来自两名重症肌无力患者的血清抗体和单克隆抗体，确定了横纹肌抗体所结合的几种抗原的生化特性。这些单克隆抗体由从胸腺和胸腺瘤获得的EB病毒转化的B淋巴细胞克隆分泌。血清抗体和单克隆抗体与骨骼肌肌节的离散成分发生反应，产生几种不同的免疫荧光染色模式。免疫印迹分析和酶联免疫吸附测定揭示了三种不同的抗体特异性：肌球蛋白、α-辅肌动蛋白和/或肌动蛋白。单个单克隆横纹肌抗体与肌动蛋白或肌球蛋白的肌肉和非肌肉同种型都发生反应。值得注意的是，收缩蛋白（1）与质膜中的乙酰胆碱受体（AChR）相关，并且（2）在转化细胞中发生生化改变。因此，可以想象，经历肿瘤转化的胸腺上皮细胞释放新抗原性的AChR相关收缩蛋白可能为横纹肌抗体的产生提供免疫原性刺激。更精确地定义个别重症肌无力和/或胸腺瘤患者的横纹肌抗体特异性可能为这些疾病的诊断和/或预后分类提供基础。此外，这些单克隆抗体将有助于通过实验测试横纹肌抗体的潜在致病性。
