Kirou Raphael A, Pinal-Fernandez Iago, Casal-Dominguez Maria, Pak Katherine, Preusse Corinna, Dari Dilbe, Del Orso Stefania, Naz Faiza, Islam Shamima, Gutierrez-Cruz Gustavo, Naddaf Elie, Liewluck Teerin, Stenzel Werner, Selva-O'Callaghan Albert, Milisenda Jose C, Mammen Andrew L
Muscle Disease Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
College of Medicine, State University of New York Downstate Health Sciences University, Brooklyn, NY, USA.
medRxiv. 2025 Feb 21:2025.02.17.25321047. doi: 10.1101/2025.02.17.25321047.
Myositis is a heterogeneous family of inflammatory myopathies. We sought to define the differential expression of cytokines, cytokine receptors, and immune checkpoint genes in muscle biopsies from patients with different forms of myositis in order to characterize patterns of inflammation in each.
Bulk RNA sequencing was performed on muscle biopsy samples from 669 patients, including 105 with dermatomyositis, 80 with immune-mediated necrotizing myopathy (IMNM), 65 with anti-synthetase syndrome, 53 with inclusion body myositis (IBM), 19 with anti-PM/Scl myositis, 310 with other inflammatory or genetic myopathies, and 37 controls with normal tissue (NT). Myositis clinical groups and autoantibody subgroups were analyzed separately. Expression data was analyzed for 338 genes encoding cytokines, cytokine receptors, and immune checkpoints. Myositis group-specific genes were identified from this list by finding genes that were specifically differentially expressed in one group compared to all samples and compared to NT (α<0.001).
IBM patients had the most differentially overexpressed genes (71) among all clinical groups, including 37 that were IBM-specific. Among the top genes were several involved in type 1 inflammation, including , and . Anti-Jo1 and anti-PM/Scl patients exhibited differential overexpression of a similar set of genes, while dermatomyositis patients exhibited differential overexpression of a different set of genes involved in type 1 inflammation. IMNM patients had the least number of differentially overexpressed genes with no predominant inflammatory pattern.
Each myositis clinical group and autoantibody subgroup had differentially overexpressed inflammatory mediators, including a strong type 1 inflammatory gene signature in IBM.
肌炎是一组异质性的炎性肌病。我们试图确定不同形式肌炎患者肌肉活检中细胞因子、细胞因子受体和免疫检查点基因的差异表达，以描绘每种肌炎的炎症模式。
对669例患者的肌肉活检样本进行批量RNA测序，其中包括105例皮肌炎患者、80例免疫介导坏死性肌病（IMNM）患者、65例抗合成酶综合征患者、53例包涵体肌炎（IBM）患者、19例抗PM/Scl肌炎患者、310例其他炎性或遗传性肌病患者以及37例正常组织（NT）对照。分别分析肌炎临床组和自身抗体亚组。对338个编码细胞因子、细胞因子受体和免疫检查点的基因的表达数据进行分析。通过找出与所有样本及NT相比在一组中特异性差异表达的基因（α<0.001），从该列表中鉴定出肌炎组特异性基因。
在所有临床组中，IBM患者差异过表达的基因最多（71个），其中37个是IBM特异性的。排名靠前的基因中有几个参与1型炎症，包括……。抗Jo1和抗PM/Scl患者表现出一组相似基因的差异过表达，而皮肌炎患者表现出另一组参与1型炎症的基因的差异过表达。IMNM患者差异过表达的基因数量最少，且无主要的炎症模式。
每个肌炎临床组和自身抗体亚组都有差异过表达的炎症介质，包括IBM中强烈的1型炎症基因特征。
