SLAM receptors regulate immune checkpoints via SAP and EAT- 2 in rheumatoid arthritis: association with disease activity.

IF 2.9 3区 医学 Q2 RHEUMATOLOGY
Mohammad Malekan, Armin Dozandeh-Jouybari, Najmeh Sadeghian, Mohsen Soltanshahi, Hossein Azadeh, Abolghasem Ajami, Hossein Asgarian-Omran, Saeid Taghiloo
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引用次数: 0

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

类风湿关节炎中SLAM受体通过SAP和EAT- 2调节免疫检查点:与疾病活动性的关系
目的: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SLAM家族受体(SLAMF1和SLAMF7)、免疫检查点分子(PD- 1和TIGIT)和含sh2的接头蛋白(SAP和EAT- 2)在类风湿关节炎(RA)中的作用及其与疾病活动性的关系。方法:共纳入50例RA患者(30例不活动,20例活动)和20例健康对照。采用实时聚合酶链反应(Real-time polymerase chain reaction, PCR)技术检测外周血单个核细胞(PBMCs)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)。评估基因表达与疾病活动评分28关节计数(DAS28)的相关性。结果: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 = 0.319, p = 0.02;R = 0.460, p = 0.0008)。RA患者PD- 1表达较高,但与DAS28无相关性,而TIGIT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。结论:SLAMF1和SLAMF7可能通过调节免疫细胞活性和细胞因子的产生参与RA的发病。PD- 1水平升高提示在免疫失调中起作用。SLAM受体、免疫检查点和接头蛋白之间的相互作用可能加剧T细胞过度活跃和慢性炎症,提供了潜在的治疗靶点。•RA患者与健康对照组相比,SLAMF1、SLAMF7、PD- 1、SAP和EAT- 2的表达明显升高。•SLAMF1和SAP的表达与疾病活动相关,在活动期RA病例中SLAMF1水平较高。•PD- 1过表达提示免疫失调,而TIGIT在RA患者中无显著差异。•SLAM受体、免疫检查点和适配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。
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来源期刊
Clinical Rheumatology
Clinical Rheumatology 医学-风湿病学
CiteScore
6.90
自引率
2.90%
发文量
441
审稿时长
3 months
期刊介绍: Clinical Rheumatology is an international English-language journal devoted to publishing original clinical investigation and research in the general field of rheumatology with accent on clinical aspects at postgraduate level. The journal succeeds Acta Rheumatologica Belgica, originally founded in 1945 as the official journal of the Belgian Rheumatology Society. Clinical Rheumatology aims to cover all modern trends in clinical and experimental research as well as the management and evaluation of diagnostic and treatment procedures connected with the inflammatory, immunologic, metabolic, genetic and degenerative soft and hard connective tissue diseases.
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