通过循环细胞外囊泡 (EV) 的表征和 EV 衍生的小非编码 RNA (sncRNA) 的表达来研究特发性炎症性肌病 (IIM) 的表观遗传足迹。在这项横断面研究中，EV 通过大小分离IIM 患者以及年龄和性别匹配的健康供体 (HD) 血浆的排阻色谱。使用下一代测序 (NGS) 对 EV 衍生的 sncRNA 进行测序和定量。质量控制和标准化后，过滤计数读数用于差异 microRNA (miRNA) 和 piwi 相互作用 RNA (piRNA) 表达分析。对 IIM 涉及的途径富集的假定基因靶点进行了分析。记录采样时患者的临床和实验室特征。纳入了 47 名 IIM 患者和 45 名 HD 患者。 miR-486-5p (p < 0.01)、miR-122-5p、miR-192-5p 和 miR-32-5p 显着上调（全部 p < 0.05），而 miR-142-3p (p < 0.001) )、miR-141-3p (p < 0.01)、let-7a-5p (p < 0.05) 和 miR-3613-5p (p < 0.05) 与 HD 患者相比，IIM 患者的 EV 中表达下调。 MiR-486-5p 与肌酶水平升高相关。 IIM 中上调/下调 miRNA 的多个靶基因参与炎症、坏死性凋亡、干扰素和免疫信号传导。与 HD 相比，IIM EV 中的 6 个 piRNA 显着失调（p < 0.05）。在 IIM 中，皮肌炎中 miR-335-5p 选择性上调，miR-27a-5p 下调（n = 21，p < 0.01）。最后，与非 CAM IIM（n = 35，p = 0.02）和 HD（p < 0.01）相比，癌症相关肌炎（CAM，n = 12）的血浆 EV 水平显着升高。 CAM 中的 EV 货物显着富集了 let-7f-5p，并耗尽了 miR-143-3p。通过对 EV 衍生的 sncRNA 进行公正的筛选，我们将 EV 货物中的 miRNA 和 piRNA 表征为潜在的生物标志物和不同 IIM 表型的修饰剂.版权所有 © 2024。由 Elsevier Ltd 出版。

To investigate the epigenetic footprint of idiopathic inflammatory myopathies (IIM) through characterization of circulating extracellular vesicles (EVs) and the expression of EV-derived small non-coding RNAs (sncRNAs).In this cross-sectional study, EVs were isolated by size-exclusion chromatography from plasma of patients with IIM and age- and sex-matched healthy donors (HD). EV-derived sncRNAs were sequenced and quantified using Next-Generation Sequencing (NGS). Following quality control and normalization, filtered count reads were used for differential microRNA (miRNA) and piwi-interacting RNA (piRNA) expression analyses. Putative gene targets enriched for pathways implicated in IIM were analyzed. Patients' clinical and laboratory characteristics at the time of sampling were recorded.Forty-seven IIM patients and 45 HD were enrolled. MiR-486-5p (p < 0.01), miR-122-5p, miR-192-5p, and miR-32-5p were significantly upregulated (p < 0.05 for all), while miR-142-3p (p < 0.001), miR-141-3p (p < 0.01), let-7a-5p (p < 0.05) and miR-3613-5p (p < 0.05) downregulated in EVs from IIM patients versus HD. MiR-486-5p was associated with raised muscle enzymes levels. Several target genes of up/downregulated miRNAs in IIM participate in inflammation, necroptosis, interferon and immune signaling. Six piRNAs were significantly dysregulated in IIM EVs versus HD (p < 0.05). Within IIM, miR-335-5p was selectively upregulated and miR-27a-5p downregulated in dermatomyositis (n = 21, p < 0.01). Finally, plasma EV levels were significantly increased in cancer-associated myositis (CAM, n = 12) versus non-CAM IIM (n = 35, p = 0.02) and HD (p < 0.01). EVs cargo in CAM was significantly enriched of let-7f-5p and depleted of miR-143-3p.Through an unbiased screening of EV-derived sncRNAs, we characterize miRNAs and piRNAs in the EVs cargo as potential biomarkers and modifiers of diverse IIM phenotypes.Copyright © 2024. Published by Elsevier Ltd.