Soluble TAM receptor tyrosine kinases in rheumatoid arthritis: Correlation with disease activity and bone destruction

Summary

The TAM receptor tyrosine kinases (TAM RTK) are a subfamily of receptor tyrosine kinases, the role of which in autoimmune diseases such as systemic lupus erythematosus has been well-explored, while their functions in rheumatoid arthritis (RA) remain largely unknown. In this study, we investigated the role of soluble TAM receptor tyrosine kinases (sAxl/sMer/sTyro3) in the patients with RA. 306 RA patients, 100 osteoarthritis (OA) patients and 120 healthy controls (HCs) were enrolled in this study. The serum concentrations of sAxl/sMer/sTyro3 were measured by ELISA, then the associations between sAxl/sMer/sTyro3 levels and clinical features of RA patients were analyzed. And we also investigated whether sTyro3 could promote osteoclast differentiation in vitro in RA patients. The results showed that comparing with HCs, sTyro3 levels in the serum of RA patients were remarkably elevated and sMer levels were significantly decreased. Whereas there was no difference between HCs and RA patients on sAxl levels. The sTyro3 levels were weakly but positively correlated with WBC, IgM, RF, swollen joint counts, tender joint counts, total sharp scores and joint erosion scores. Conversely, there were no significant correlations between sMer levels and the above indices. Moreover, RA patients with high disease activity also showed higher sTyro3 levels. In vitro osteoclast differentiation assay further showed that TRAP⁺ osteoclasts were significantly increased in the presence of sTyro3. Collectively, our study indicated that sTyro3 levels were elevated in RA patients and positively correlated with disease activity and bone destruction, which may serve as an important participant in RA pathogenesis. This article is protected by copyright. All rights reserved.