PT - JOURNAL ARTICLE AU - Felix Kleefeld AU - Akinori Uruha AU - Anne Schänzer AU - Anna Nishimura AU - Andreas Roos AU - Udo Schneider AU - Hans H. Goebel AU - Markus Schuelke AU - Katrin Hahn AU - Corinna Preusse AU - Werner Stenzel TI -线粒体病理和包涵体肌炎的形态学和分子模式[j] . 201103 /WNL.0000000000201103DP - 2022 11月15日TA - N半岛投注体育官网eurology PG - e2212—e2222 VI - 99 IP - 204099 - //www.ebmtp.com/content/99/20/e2212.short 4100 - //www.ebmtp.com/content/99/20/e2212.full SO - Neurology2022 11月15日;背景和目的:通过与散发性包涵体肌炎(IBM)的比较，研究线粒体病理(PM-Mito)多肌炎的形态学和分子基础，并通过干扰素(IFN)相关炎症和t细胞反应来定义常见和独特的病理生理特征。方法在这项横断面研究中，分析了德国柏林慈善大学医院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、相同数量的随机选择的IBM活检样本和随机选择的非患病对照(ndc)被纳入研究。通过组织病理学、免疫组织化学和定量PCR (qPCR)对活检标本进行研究，并与ndc活检标本进行比较。主要结果包括qPCR的免疫组化细胞计数和基因表达(与ndc相比的折叠变化值)。结果25例PM-Mito和IBM患者的骨骼肌活检样本被纳入研究，并与5例NDCs的活检样本进行了比较。PM-Mito和IBM在定性上有着惊人的相似的分子特征，并共享重要的组织病理学特征。ifn诱导的鸟苷酸结合蛋白(GBP)6和t细胞功能相关的KLRG1的表达将IBM与PM-Mito活检区分出来，IBM患者的GBP6和KLRG1的表达明显更高。在两组患者中均检测到隐外显子表达，其中IBM患者的表达水平较高。 Skeletal muscle biopsies from IBM patients showed significantly more GBP6+ cells and KLRG1+ lymphocytes in comparison with biopsies from patients with PM-Mito. 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