AB0046 THE EXPRESSION AND CLINICAL SIGNIFICANCE OF TAM RECEPTOR TYROSINE KINASE ON MONOCYTE SUBSETS IN RHEUMATOID ARTHRITIS
Authors: J. Xue, L. Xu, F. Hu, Y. Su
Journal: Annals of the Rheumatic Diseases (2021)

Background: The TAM receptor tyrosine kinases (Tyro3/Axl/Mer TK) 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 [1]. Objectives: The study aimed to investigate the expression and clinical significance of Tyro3, Axl and MerTK on monocyte subsets in rheumatoid arthritis (RA). Methods: The expression of Tyro3, Axl and MerTK on CD14+ monocytes, nonclassical monocytes (NCM, CD14 + CD16 ++ ), intermediate monocytes (IM, CD14 ++ CD16 + ), and classical monocytes (CM, CD14 ++ CD16 - ) were evaluated in peripheral blood of RA by flow cytometry and qPCR. And the correlation between the expression of Tyro3TK and MerTK on NCM, IM, and CM with RA patient clinical feature were further analyzed. Results: The results revealed that the expression of Tyro3TK on CD14+ monocytes was significantly upregulated in RA patients (F = 9.18, P &lt; 0.0001), while there was no significant difference of the expression MerTK on HC, OA, and RA, and the expression of AxlTK was minimal (Fig 1). The expression of Tyro3TK on CM was significantly upregulated in RA patients as compared with HC and osteoarthritis (OA) patients (P &lt; 0.05, Fig 2-3), and positively correlated with the disease manifestations, such as swollen joint count (SJC), tender joint count (TJC) and the disease activity score (Fig 4). Figure 1. The expression of Tyro3, Axl and MerTK on CD14+ monocytes is increased in RA. (a ) Gating strategy for flow cytometry of Tyro3, Axl and MerTK on CD14+ monocytes. (b ) The expression of Tyro3, Axl and MerTK on CD14+ monocytes were compared between HC (n = 40), OA (n = 27), and RA patients (n = 40). * P &lt; 0.05, ** P &lt; 0.01, ns, not significant. Figure 2. The expression of Tyro3TK on IM and CM were increased in RA. (a ) Gating strategy for flow cytometry of TAMTK on monocyte subsets. The expression of (b ) Tyro3TK and (c ) MerTK on NCM, IM, and CM were compared between HC (n = 40), OA (n = 27), and RA patients (n = 40). *P &lt; 0.05, ** P &lt; 0.01, *** P &lt; 0.001, ns, not significant. Figure 3. The mRNA expression of Tyro3TK on CM is increased in RA. (a ) The mRNA expression of Tyro3TK on NCM, IM, and CM in HC (n = 3) and RA (n = 3) patients. (b ) The mRNA expression of MerTK on NCM, IM, and CM in HC (n = 3) and RA (n = 3) patients. ** P &lt; 0.01. Conclusion: These findings indicate that Tyro3TK on CM was elevated in RA patients and correlated positively with disease activity, which may serves as an important participant in RA pathogenesis. References: [1]Rothlin CV, Lemke G, TAM receptor signaling and autoimmune disease. Curr Opin Immunol, 2010. 22(6): p. 740-6. Footnotes: The study was supported by grants from the National Natural Science Foundation of China (81671609 and 81871290 to Dr. Y. Su, 82001718 to Dr. L. Xu), the Beijing Science and Technology Planning Project (Z191100006619111 to Dr. Y. Su), the Beijing Municipal Natural Science Foundation (7194329 to Dr. L. Xu). Figure 4. Correlation analysis of Tyro3TK on IM and CM with RA patient clinical manifestations. The associations of Tyro3TK on IM (r = 0.492, * P = 0.001) (a ) and CM (r = 0.577, * P = 0.0001) (b ) with RA patient swollen joint counts (SJC) were analyzed, respectively. The expression of Tyro3TK on IM and CM were also compared between different RA patient groups: (c ) RA with high disease activity (DAS28-ESR &gt; 3.2) and non-high disease activity (DAS28-ESR ≤ 3.2), (d ) RA with and without swollen joints, (e) tender joints. * P &lt; 0.05, ** P &lt; 0.01. Disclosure of Interests: None declared