RT期刊文章SR电子T1形态学和分子模式线粒体多肌炎的病理和包涵体肌炎摩根富林明神经病学神经学乔FD Lippincott Williams &威尔金斯SP e2212 OP e2222 10.1212 / WNL。半岛投注体育官网99签证官0000000000201103是20 A1 Felix Kleefeld A1 Akinori Uruha保持A1安妮Schanzer A1安娜西村A1 Andreas鲁斯A1 Udo施耐德A1汉斯·h·Goebel A1马库斯Schuelke A1凯特琳哈恩A1科琳娜Preusse A1 Werner Stenzel年2022 UL //www.ebmtp.com/content/99/20/e2212.abstract AB背景和客观描述与线粒体多半岛投注体育官网肌炎病理形态学和分子基础(PM-Mito)相比,零星的包涵体肌炎(IBM)和定义不同的病理学特点与公共关注干扰素(IFN)相关的炎症和t细胞反应。横断面研究方法,骨骼肌活检样本从PM-Mito患者和临床和实验室数据,并分析了IBM查利特大学医院在柏林,德国。所有可用PM-Mito活检样本,同等数量的随机选择IBM活检样本,并随机选择nondiseased控制(ndc)包括在这项研究。活检样本研究组织病理学、免疫组织化学和定量PCR (qPCR)并与活检来自国防委员会。主要包括细胞计数结果免疫组织化学和基因表达(叠化值与ndc) qPCR。结果25骨骼肌活检的患者样本PM-Mito和IBM被包括在研究并与5 ndc活检样本。PM-Mito和IBM定性存在惊人的相似的分子签名和共享的重要病理特征。表达IFN-induced guanylate-binding蛋白(英镑)6和t细胞function-related KLRG1杰出IBM从PM-Mito活检患者显示明显高于6和KLRG1英镑的表情。神秘的外显子表达式中检测出两个病人组与IBM患者表现出较高的表达水平。来自IBM的骨骼肌活检患者还表现出了明显的6英镑+细胞和KLRG1 +淋巴细胞相比,从PM-Mito患者活检。 CD45+, CD68+, CD57+, PD1+, and CD8+ cytotoxic T cells were also significantly more abundant in patients with IBM. Clinically, patients with PM-Mito presented with a spectrum of muscle-related symptoms including myalgia, proximal paraparesis, proximal tetraparesis, and incomplete IBM-like patterns. Thirteen of 14 (93%) patients with PM-Mito for whom clinical follow-up was available later developed clinically defined IBM. Notably, 2 follow-up biopsies obtained 5 and 7 years after the first ones were available in this cohort, both showing histopathologic progress to net IBM including GBP6 and KLRG1 upregulation.Discussion Our combined data suggest that specific IFN-mediated inflammation plays a key role in both IBM and PM-Mito. GBP6 was identified as a new molecule of type II IFN-induced inflammation distinguishing IBM from PM-Mito. Skeletal muscles from both groups harbor dysfunctional T cells of similar type, albeit in different quantity. T-cell senescence exemplified by KLRG1 positivity does not play a significant role in PM-Mito. Based on these findings, we propose to include PM-Mito in the spectrum of IBM (IBM-spectrum disease [IBM-SD]) as a possible early form of this disease. The establishment of IBM-SD as a larger entity could potentially have a significant effect on the design of trials and therapeutic interventions.CK=creatine kinase; GBP6=guanylate-binding protein 6; IBM=inclusion body myositis; IBM-SD=IBM-spectrum disease; MHC=major histocompatibility complex; NDC=nondiseased control; PM-Mito=polymyositis with mitochondrial pathology; qPCR=quantitative PCR; TDP-43=transactivation response element DNA binding protein 43