Zhou Yueyuan, Zhao Yangfan, Yin Geng, Kang Limei, Zhu Xiaoyan, Xie Qibing
Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
School of Physics & Electronics, Hunan University, Changsha, Hunan, China.
Clin Exp Rheumatol. 2025 Feb;43(2):241-250. doi: 10.55563/clinexprheumatol/hlk85n. Epub 2024 Sep 13.
Idiopathic inflammatory myopathy (IIM) is a group of systemic autoimmune diseases characterised by muscle involvement. This study aims to reveal the characteristics of IIM subtypes and explore the molecular mechanisms underlying IIM.
The STRING database was utilised to construct a protein-protein interaction network of differentially expressed genes obtained from the GSE128470, GSE3112, and GSE39454 datasets. The immune cell infiltration level was assessed by CIBERSORT in polymyositis (PM). Experimental autoimmune myositis (EAM) model mice were constructed for experimental verification. Serum levels of soluble CD44 (sCD44) were measured using enzyme-linked immunosorbent assay.
The upregulated hub gene CD44 was highly expressed in inflammatory cells infiltrating the skeletal muscle of patients with PM and in EAM mice. CD44 was correlated with both M1 macrophages (r=0.57, p<0.0001) and M2 macrophages (r=0.57, p<0.0001) in PM. Additionally, CD44+F4/80+ macrophages in skeletal muscle were increased (p<0.0001) and CD44 showed a stronger association with markers of M1 macrophage in EAM mice. Moreover, serum sCD44 levels were elevated in patients with IIM (p=0.0024), PM (p=0.0332) and dermatomyositis (p=0.0001) notably in the anti-melanoma differentiation-associated gene 5 antibody positive subtype (p=0.0007). sCD44 levels also positively correlated with visual analogue score (r=0.4424, p=0.0013), myositis intention to treat activity index (r=0.3938, p=0.0047), skin damage score (r=0.3796, p=0.0101) and skin activity score (r=0.4625, p=0.0014) in patients with IIM.
This study suggests that macrophages expressing CD44 may be involved in the pathogenesis of PM, and sCD44 could serve as a potential marker for skin damage and activity in IIM.
特发性炎性肌病（IIM）是一组以肌肉受累为特征的系统性自身免疫性疾病。本研究旨在揭示IIM亚型的特征，并探索IIM潜在的分子机制。
利用STRING数据库构建从GSE128470、GSE3112和GSE39454数据集中获得的差异表达基因的蛋白质-蛋白质相互作用网络。通过CIBERSORT评估多发性肌炎（PM）中的免疫细胞浸润水平。构建实验性自身免疫性肌炎（EAM）模型小鼠用于实验验证。采用酶联免疫吸附测定法检测血清可溶性CD44（sCD44）水平。
上调的枢纽基因CD44在PM患者骨骼肌浸润的炎性细胞以及EAM小鼠中高表达。在PM中，CD44与M1巨噬细胞（r = 0.57，p < 0.0001）和M2巨噬细胞（r = 0.57，p < 0.0001）均相关。此外，骨骼肌中CD44 + F4/80 +巨噬细胞增加（p < 0.0001），且在EAM小鼠中CD44与M1巨噬细胞标志物的关联更强。此外，IIM患者（p = 0.0024）、PM患者（p = 0.0332）和皮肌炎患者（p = 0.0001）血清sCD44水平升高，在抗黑色素瘤分化相关基因5抗体阳性亚型中尤为明显（p = 0.0007）。在IIM患者中，sCD44水平还与视觉模拟评分（r = 0.4424，p = 0.0013）、肌炎意向性治疗活动指数（r = 0.3938，p = 0.0047）、皮肤损伤评分（r = 0.3796，p = 0.0101）和皮肤活动评分（r = 0.4625，p = 0.0014）呈正相关。
本研究表明，表达CD44的巨噬细胞可能参与PM的发病机制，且sCD44可作为IIM皮肤损伤和活动的潜在标志物。
