Love L A, Leff R L, Fraser D D, Targoff I N, Dalakas M, Plotz P H, Miller F W
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Medicine (Baltimore). 1991 Nov;70(6):360-74. doi: 10.1097/00005792-199111000-00002.
The IIM are a heterogeneous group of systemic rheumatic diseases which share the common features of chronic muscle weakness and mononuclear cell infiltrates in muscle. A number of classification schemes have been proposed for them, but none takes into consideration the marked immunologic, clinical, and genetic heterogeneity of the various clinical groups. We compared the usefulness of myositis-specific autoantibodies (anti-aminoacyl-tRNA synthetases, anti-SRP, anti-Mi-2 and anti-MAS) to the standard clinical categories (polymyositis, dermatomyositis, overlap myositis, cancer-associated myositis, and inclusion body myositis) in predicting clinical signs and symptoms, HLA types, and prognosis in 212 adult IIM patients. Although patients with inclusion body myositis (n = 26) differed in having significantly more asymmetric and distal weakness, falling, and atrophy than other patients, there were few other significant differences among the other clinical groups. In contrast, autoantibody status defined distinct sets of patients and each patient had only 1 myositis-specific autoantibody. Patients with anti-amino-acyl-tRNA synthetase autoantibodies (n = 47), compared to those without these antibodies, had significantly more frequent arthritis, fever, interstitial lung disease, and "mechanic's hands"; HLA-DRw52; higher mean prednisone dose at survey, higher proportion of patients receiving cytotoxic drugs, and higher death rates. Those with anti-signal recognition particle antibodies (n = 7) had increased palpitations; myalgias; DR5, DRw52; severe, refractory disease; and higher death rates. Patients with anti-Mi-2 antibodies (n = 10) had increased "V-sign" and "shawl-sign" rashes, and cuticular overgrowth; DR7 and DRw53; and a good response to therapy. The 2 patients with anti-MAS antibodies were the only ones with alcoholic rhabdomyolysis preceding myositis; both had insulin-dependent diabetes mellitus, and both had HLA-B60, -C3, -DR4, and -DRw53. These findings suggest that myositis-specific autoantibody status is a more useful guide than clinical group in assessing patients with myositis, and that specific associations of immunogenetics, immune responses, and clinical manifestations occur in IIM. Thus the myositis-specific autoantibodies aid in interpreting the diverse symptoms and signs of myositis patients and in predicting their clinical course and prognosis. We propose, therefore, that an adjunct classification of the IIM, based on the myositis-specific autoantibody status, be incorporated into future studies of their epidemiology, etiology, and therapy.
炎性肌病是一组异质性的系统性风湿性疾病，具有慢性肌无力和肌肉单核细胞浸润的共同特征。已经提出了多种针对它们的分类方案，但没有一种方案考虑到不同临床组显著的免疫、临床和遗传异质性。我们比较了肌炎特异性自身抗体（抗氨酰tRNA合成酶、抗信号识别颗粒、抗Mi-2和抗MAS）与标准临床分类（多发性肌炎、皮肌炎、重叠性肌炎、癌症相关性肌炎和包涵体肌炎）在预测212例成年炎性肌病患者的临床体征和症状、HLA类型及预后方面的作用。虽然包涵体肌炎患者（n = 26）与其他患者相比，有明显更多的不对称性和远端肌无力、跌倒及萎缩，但其他临床组之间几乎没有其他显著差异。相比之下，自身抗体状态界定了不同的患者组，且每个患者仅有1种肌炎特异性自身抗体。与无抗氨酰tRNA合成酶自身抗体的患者相比，有该抗体的患者（n = 47）关节炎、发热、间质性肺病及“技工手”更为常见；有HLA-DRw52；在调查时平均泼尼松剂量更高，接受细胞毒性药物治疗的患者比例更高，死亡率也更高。有抗信号识别颗粒抗体的患者（n = 7）有心悸增加；肌痛；有DR5、DRw52；有严重的难治性疾病；死亡率也更高。有抗Mi-2抗体的患者（n = 10）“V征”和“披肩征”皮疹及表皮过度生长增加；有DR7和DRw53；对治疗反应良好。2例有抗MAS抗体的患者是仅有的在肌炎之前发生酒精性横纹肌溶解的患者；二者均为胰岛素依赖型糖尿病，且均有HLA-B60、-C3、-DR4和-DRw53。这些发现提示，在评估肌炎患者时，肌炎特异性自身抗体状态比临床分组是更有用的指导，且在炎性肌病中存在免疫遗传学、免疫反应及临床表现的特定关联。因此，肌炎特异性自身抗体有助于解释肌炎患者的各种症状和体征，并预测其临床病程及预后。因此，我们建议，基于肌炎特异性自身抗体状态的炎性肌病辅助分类应纳入其未来的流行病学、病因学及治疗研究中。
