Tyro3 upregulation is associated with muscle involvement in patients with idiopathic inflammatory myopathies

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.

Idiopathic inflammatory myopathies; Muscle injury; Necrosis; Tyro3.