{"title":"SLAM receptors regulate immune checkpoints via SAP and EAT- 2 in rheumatoid arthritis: association with disease activity.","authors":"Mohammad Malekan, Armin Dozandeh-Jouybari, Najmeh Sadeghian, Mohsen Soltanshahi, Hossein Azadeh, Abolghasem Ajami, Hossein Asgarian-Omran, Saeid Taghiloo","doi":"10.1007/s10067-025-07461-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":10482,"journal":{"name":"Clinical Rheumatology","volume":" ","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Rheumatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10067-025-07461-5","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
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.
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.