Liu Huan, Ren Ying, Li Qianwei, Si Yanjun, Chen Yuehong, Dong Min, Yin Geng, Xie Qibing
Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Number 37 Guoxue Alley in the Wuhou District, Chengdu, 610041, China.
Department of Outpatient, West China Hospital, Sichuan University, Chengdu, 610041, China.
Immunol Res. 2025 Sep 16;73(1):131. doi: 10.1007/s12026-025-09688-5.
Tyro3, Axl, and Mer (TAM) receptors are involved in immunity and affect the progression of several autoimmune diseases. This study investigated the potential role of TAM receptors in individuals diagnosed with idiopathic inflammatory myopathies (IIM). Clinical data and serum samples were obtained from 176 patients with IIM and 50 healthy controls (HCs). The levels of soluble TAM (sTAM) receptors were measured through enzyme-linked immunosorbent assay. Additionally, Tyro3 protein expression in the muscle tissue of both patients and HCs was examined using western blot and immunohistochemistry (IHC) analyses. The levels of sTAM receptors were notably higher in IIM patients than in HCs. Specifically, serum concentrations of soluble Tyro3 (sTyro3) were markedly elevated among patients with dermatomyositis (DM) and immune-mediated necrotizing myopathy (IMNM). No significant differences were found in sTyro3 levels among IMNM patients with anti-signal recognition particle positive, anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase positive, and seronegative subtypes. Further, levels of sTyro3 showed an inverse relationship with the manual muscle testing-8 score, while exhibiting a positive correlation with serum creatine kinase. Following treatment, patients with IMNM and DM exhibited reduced sTyro3 levels. Results from western blotting and IHC revealed a significant expression of Tyro3 in the necrotic muscles of patients with IMNM and DM. This study demonstrated that Tyro3 causes muscle injury in patients with IIM; therefore, it is considered a potential biomarker and therapeutic target for patients with IIM.
酪氨酸激酶3(Tyro3)、AXL受体酪氨酸激酶(Axl)和Mer酪氨酸激酶(Mer)(TAM)受体参与免疫过程,并影响多种自身免疫性疾病的进展。本研究调查了TAM受体在诊断为特发性炎性肌病(IIM)的个体中的潜在作用。收集了176例IIM患者和50例健康对照(HC)的临床数据和血清样本。通过酶联免疫吸附测定法测量可溶性TAM(sTAM)受体的水平。此外,使用蛋白质免疫印迹法和免疫组织化学(IHC)分析检测患者和HC肌肉组织中Tyro3蛋白的表达。IIM患者的sTAM受体水平显著高于HC。具体而言,皮肌炎(DM)和免疫介导的坏死性肌病(IMNM)患者的可溶性Tyro3(sTyro3)血清浓度明显升高。抗信号识别颗粒阳性、抗3-羟基-3-甲基戊二酰辅酶A还原酶阳性和血清阴性亚型的IMNM患者的sTyro3水平未发现显著差异。此外,sTyro3水平与徒手肌力测试-8评分呈负相关,而与血清肌酸激酶呈正相关。治疗后,IMNM和DM患者的sTyro3水平降低。蛋白质免疫印迹法和IHC结果显示,IMNM和DM患者的坏死肌肉中Tyro3有显著表达。本研究表明,Tyro3会导致IIM患者的肌肉损伤;因此,它被认为是IIM患者的潜在生物标志物和治疗靶点。