A novel autoantibody recognizing 200-kd and 100-kd proteins is associated with an immune-mediated necrotizing myopathy.
A novel autoantibody recognizing 200-kd and 100-kd proteins is associated with an immune-mediated necrotizing myopathy.
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DOI：
10.1002/art.27572
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发表时间：
2010-09
影响因子：
--
通讯作者：
Mammen, Andrew L.
中科院分区：
文献类型：
--
作者：
Christopher-Stine, Lisa;Casciola-Rosen, Livia A.;Hong, Grace;Chung, Tae;Corse, Andrea M.;Mammen, Andrew L.
无明显炎症的肌纤维坏死是在营养不良和毒性或免疫介导的肌病患者中观察到的非特异性发现。然而，坏死性肌病的病因往往是模糊的，哪些患者将受益于免疫抑制仍然不确定。我们试图在坏死性肌病患者中鉴定新的自身抗体。对225例肌病患者进行了肌肉活检和血清学检查。通过从35 S-甲硫氨酸标记的HeLa细胞裂解物进行免疫沉淀来确定抗体特异性。对选定的活检组织进行膜攻击复合物（MAC）、主要组织相容性复合物I（MHC I）和内皮细胞标志物CD 31染色。225例患者中38例在肌肉活检中以肌纤维坏死为主。其中12例具有已知的自身抗体关联或其肌病的其他病因。其余26份血清中的16份免疫沉淀200和100 kDa蛋白;仅在1/187例无坏死性肌病患者中发现这种特异性。抗200/100特异性的患者有近端无力（100%）、高肌酸激酶（CK）水平（平均10，333 IU/L）和肌电图（EMG）上的易激性肌病（88%）。63%在虚弱发作前暴露于他汀类药物。所有患者均对免疫抑制治疗有反应，许多患者随着药物逐渐减少而复发。免疫组织化学研究显示MAC在6/8的小血管和4/8的非坏死肌纤维表面上。5/8例毛细血管形态异常，4/8例非坏死肌纤维表面表达MHC I。抗200/100 kDa特异性定义了坏死性肌病患者的一个亚组，以前被认为是“自身抗体阴性”。“我们认为这些患者患有免疫介导的肌病，通常与既往使用他汀类药物有关，应接受免疫抑制治疗。
Myofiber necrosis without prominent inflammation is a non-specific finding seen in patients with dystrophies and toxic or immune-mediated myopathies. However, the etiology of a necrotizing myopathy is often obscure and which patients would benefit from immunosuppression remains uncertain. We sought to identify novel autoantibodies in necrotizing myopathy patients. Muscle biopsy and serum were available for 225 myopathy patients. Antibody specificities were determined by performing immunoprecipitations from 35S-methionine-labeled HeLa cell lysates. Selected biopsies were stained for membrane attack complex (MAC), major histocompatability complex I (MHC I), and endothelial cell marker CD31. 38 of 225 patients had predominant myofiber necrosis on muscle biopsy. 12 of these had a known autoantibody association or other etiology for their myopathy. 16 of the remaining 26 sera immunoprecipitated 200 and 100 kDa proteins; this specificity was found in only 1/187 patients without necrotizing myopathy. Patients with anti-200/100 specificity had proximal weakness (100%), high creatine kinase (CK) levels (mean 10,333 IU/L), and an irritable myopathy on electromyography (EMG) (88%). 63% had exposure to statins prior to the onset of weakness. All patients responded to immunosuppressive therapy and many relapsed with medication tapering. Immunohistochemical studies showed MAC on small blood vessels in 6/8 and on the surface of non-necrotic myofibers in 4/8. 5/8 had abnormal capillary morphology and 4/8 expressed MHC I on the surface of non-necrotic myofibers. An anti-200/100 kDa specificity defines a subgroup of necrotizing myopathy patients previously considered to be "autoantibody negative." We propose that these patients have an immune-mediated myopathy which is frequently associated with prior statin use and should be treated with immunosuppressive therapy.
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影响因子：
11.2
作者：
EMSLIESMITH, AM;ENGEL, AG
通讯作者：
ENGEL, AG
影响因子：
27.4
作者：
Hengstman, G. J. D.;ter Laak, H. J.;van Engelen, B. G. M.
通讯作者：
van Engelen, B. G. M.
影响因子：
2.8
作者：
Needham, Merrilee;Fabian, Victoria;Mastaglia, Frank L.
通讯作者：
Mastaglia, Frank L.
影响因子：
3.3
作者：
OXENHANDLER, R;HART, MN;IRVIN, W
通讯作者：
IRVIN, W
影响因子：
--
作者：
Kao, AH;Lacomis, D;Oddis, CV
通讯作者：
Oddis, CV