@文章{Kleefelde2212，作者= {Felix Kleefeld和Akinori Uruha和Anne Sch{\"a}nzer和Anna Nishimura和Andreas Roos和Udo Schneider和Hans H. Goebel和Markus Schuelke和Katrin Hahn和Corinna Preusse和Werner Stenzel}，标题={线粒体病理和包涵体肌炎的形态学和分子模式}，卷={99}，编号={20}，页= {e2212—e2222}，年= {2022}，doi = {10.1212/WNL。0000000000201103}，出版商= {Wolters Kluwer Health, Inc.代表美国神经病学学会}，摘要={背景和目的:与散发的包涵体肌炎(IBM)相比，描述线粒体病理半岛投注体育官网学多发性肌炎(PM-Mito)的形态学和分子基础，并定义共同和不同的病理生理特征，重点关注干扰素(IFN)相关的炎症和t细胞反应。方法在这项横断面研究中，分析了德国柏林Charit大学医院PM-Mito和IBM患者的骨骼肌活检样本和临床和实验室数据。所有可用的PM-Mito活检样本、等量随机选择的IBM活检样本和随机选择的非患病对照(NDCs)均纳入研究。活检样本通过组织病理学、免疫组织化学和定量PCR (qPCR)进行研究，并与NDCs活检进行比较。主要结果包括免疫组化的细胞计数和qPCR的基因表达(与NDCs相比的折叠变化值)。结果25例PM-Mito和IBM患者骨骼肌活检样本被纳入研究，并与5例ndc患者的活检样本进行了比较。PM-Mito和IBM在定性上具有惊人相似的分子特征和共同的重要组织病理学特征。ifn诱导的鸟苷后期结合蛋白(GBP)6的表达和t细胞功能相关的KLRG1将IBM与PM-Mito活检区别开，IBM患者的GBP6和KLRG1表达明显更高。两组患者均检测到隐性外显子表达，IBM患者表达水平较高。与PM-Mito患者的骨骼肌活检相比，IBM患者的骨骼肌活检显示更多的GBP6+细胞和KLRG1+淋巴细胞。 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}, issn = {0028-3878}, URL = {//www.ebmtp.com/content/99/20/e2212}, eprint = {//www.ebmtp.com/content/99/20/e2212.full.pdf}, journal = {Neurology} }