Objective. To investigate the role of TAM receptors in rheumatoid arthritis (RA) by determining synovial tissue TAM receptor expression, synovial fluid levels of soluble TAM receptors, and the relationship between soluble TAM receptors, joint inflammation and disease activity. Methods. TAM receptor expression was determined by immunohistochemistry on the synovium from RA and osteoarthritis (OA) patients. Soluble (s) Tyro3, sAxl, sMer, and their ligand Gas6 were measured by ELISA in the synovial fluid of RA () and OA () patients and cytokine levels by multiplex immunoassay in RA samples. Correlation analyses were performed among sTAM receptors with local cytokine levels; systemic disease parameters like erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and anticyclic citrullinated peptide antibodies (ACPA); and disease activity scores (DAS28-ESR) in RA patients. Results. TAM receptors were expressed on different locations in the synovial tissue (lining, sublining, and blood vessels), and a similar expression pattern was observed in RA and OA patients. Synovial fluid sTyro3 and sMer were significantly enhanced in RA compared to OA patients, whereas no significant differences in sAxl and Gas6 levels were found. In RA samples, sTyro3 levels, but not sMer, correlated positively with proinflammatory local cytokines and the systemic factor erythrocyte sedimentation rate. Moreover, stratification analysis showed high sTyro3 levels positively correlated with higher DAS28-ESR and in RF and ACPA double positive RA patients. Conclusion. sTyro3 in the synovial fluid of RA patients correlates with local inflammatory molecules and systemic disease activity. These findings suggest that the reduced negative control of cell activation by TAM receptors due to their shedding in the synovial fluid, mainly sTyro3, favoring joint inflammation in RA patients.

中文翻译：

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滑膜可溶性 TYRO3 的选择性增加与类风湿性关节炎患者的疾病严重程度和关节炎症相关。

客观。通过确定滑膜组织 TAM 受体的表达、可溶性 TAM 受体的滑液水平以及可溶性 TAM 受体、关节炎症和疾病活动之间的关系，研究 TAM 受体在类风湿性关节炎 (RA) 中的作用。方法。TAM 受体表达通过免疫组织化学对 RA 和骨关节炎 (OA) 患者的滑膜进行测定。可溶性 (s) Tyro3、sAxl、sMer 及其配体 Gas6 通过 ELISA 测定在 RA 的滑液中（)和 OA () RA 样本中通过多重免疫测定法测定的患者和细胞因子水平。在 sTAM 受体与局部细胞因子水平之间进行相关性分析；全身性疾病参数，如红细胞沉降率 (ESR)、类风湿因子 (RF) 和抗环瓜氨酸肽抗体 (ACPA)；RA患者的疾病活动评分（DAS28-ESR）。结果. TAM 受体在滑膜组织（衬里、下衬里和血管）的不同位置表达，在 RA 和 OA 患者中观察到类似的表达模式。与 OA 患者相比，RA 患者的滑液 sTyro3 和 sMer 显着增强，而 sAxl 和 Gas6 水平没有发现显着差异。在 RA 样本中，sTyro3 水平（而非 sMer）与促炎局部细胞因子和全身因子红细胞沉降率呈正相关。此外，分层分析显示高 sTyro3 水平与较高的 DAS28-ESR 以及在 RF 和 ACPA 双阳性 RA 患者中呈正相关。结论. RA 患者滑液中的 sTyro3 与局部炎症分子和全身疾病活动相关。这些发现表明，TAM 受体对细胞活化的负控制减少，因为它们在滑液中脱落，主要是 sTyro3，有利于 RA 患者的关节炎症。