Malekan Mohammad, Dozandeh-Jouybari Armin, Sadeghian Najmeh, Soltanshahi Mohsen, Azadeh Hossein, Ajami Abolghasem, Asgarian-Omran Hossein, Taghiloo Saeid
Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Clin Rheumatol. 2025 Apr 26. doi: 10.1007/s10067-025-07461-5.
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and immune dysregulation. This study aimed to investigate the role of SLAM family receptors (SLAMF1 and SLAMF7), immune checkpoint molecules (PD- 1 and TIGIT), and SH2-containing adaptor proteins (SAP and EAT- 2) in rheumatoid arthritis (RA) and their association with disease activity.
A total of 50 RA patients (30 inactive, 20 active) and 20 healthy controls were enrolled. Real-time polymerase chain reaction (PCR) was used to assess the expression of target genes in peripheral blood mononuclear cells (PBMCs). Gene expression profiling datasets (GSE77298, GSE206848, GSE236924, GSE15573) were analyzed to identify differentially expressed genes (DEGs). Correlation of gene expression with Disease Activity Score 28-joint count (DAS28) was evaluated.
SLAMF1, SLAMF7, SAP, and EAT- 2 expression levels were significantly elevated in RA patients compared to controls. SLAMF1 and SAP expression correlated positively with DAS28 (r = 0.319, p = 0.02; r = 0.460, p = 0.0008, respectively). PD- 1 expression was higher in RA patients but showed no correlation with DAS28, while TIGIT expression was not significantly different. Bioinformatics analysis revealed significant upregulation of SLAMF7 and TIGIT in synovial tissues from RA patients.
SLAMF1 and SLAMF7 appear to contribute to RA pathogenesis by modulating immune cell activity and cytokine production. Elevated PD- 1 levels suggest a role in immune dysregulation. The interplay between SLAM receptors, immune checkpoints, and adaptor proteins may exacerbate T cell overactivity and chronic inflammation, offering potential therapeutic targets. Key Points •RA patients showed significantly higher expression of SLAMF1, SLAMF7, PD- 1, SAP, and EAT- 2 compared to healthy controls. •SLAMF1 and SAP expression correlated with disease activity, with SLAMF1 levels higher in active RA cases. •PD- 1 overexpression suggested immune dysregulation, while TIGIT showed no significant difference in RA patients. •The interplay between SLAM receptors, immune checkpoints, and adaptor proteins may contribute to RA pathogenesis and serve as potential therapeutic targets.
类风湿关节炎（RA）是一种以慢性炎症和免疫失调为特征的自身免疫性疾病。本研究旨在探讨信号淋巴细胞激活分子家族受体（SLAMF1和SLAMF7）、免疫检查点分子（PD-1和TIGIT）以及含SH2结构域的衔接蛋白（SAP和EAT-2）在类风湿关节炎（RA）中的作用及其与疾病活动度的关联。
共纳入50例RA患者（30例病情缓解，20例病情活动）和20例健康对照。采用实时聚合酶链反应（PCR）评估外周血单个核细胞（PBMCs）中靶基因的表达。分析基因表达谱数据集（GSE77298、GSE206848、GSE236924、GSE15573）以鉴定差异表达基因（DEGs）。评估基因表达与28个关节疾病活动评分（DAS28）的相关性。
与对照组相比，RA患者中SLAMF1、SLAMF7、SAP和EAT-2的表达水平显著升高。SLAMF1和SAP的表达与DAS28呈正相关（r分别为0.319，p = 0.02；r为0.460，p = 0.0008）。RA患者中PD-1的表达较高，但与DAS28无相关性，而TIGIT的表达无显著差异。生物信息学分析显示RA患者滑膜组织中SLAMF7和TIGIT显著上调。
SLAMF1和SLAMF7似乎通过调节免疫细胞活性和细胞因子产生而参与RA的发病机制。PD-1水平升高提示其在免疫失调中起作用。SLAM受体、免疫检查点和衔接蛋白之间的相互作用可能会加剧T细胞过度活化和慢性炎症，提供了潜在的治疗靶点。要点：•与健康对照相比，RA患者中SLAMF1、SLAMF7、PD-1、SAP和EAT-2的表达显著更高。•SLAMF1和SAP的表达与疾病活动度相关，活动期RA病例中SLAMF1水平更高。•PD-1过表达提示免疫失调，而RA患者中TIGIT无显著差异。•SLAM受体、免疫检查点和衔接蛋白之间的相互作用可能有助于RA的发病机制，并作为潜在的治疗靶点。
