Felix Kleefeld % 0期刊文章% %一个安妮Schanzer Akinori Uruha保持% %一个安娜西村% Andreas鲁斯%一个汉斯·h·Goebel Udo施耐德% % Markus Schuelke % %凯特琳哈恩一科琳娜Preusse % Werner Stenzel % T与线粒体多肌炎病理形态学和分子模式和包涵体肌炎% D R 10.1212 / WNL 2022%。0000000000201103 % J半岛投注体育官网神经病学% P e2212-e2222 % V 99% N 20% X背景和客观描述与线粒体多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 %U //www.ebmtp.com/content/neurology/99/20/e2212.full.pdf