CCR5 + T cells as a potential biomarker for primary Sjögren’s disease based on bioinformatics analysis

被引:0
作者
Huixin Dou [1 ]
Ruiqing Wu [1 ]
Hao Wang [1 ]
Xiaoyan Wang [1 ]
Yingying Su [1 ]
机构
[1] Department of Stomatology, Beijing Tiantan Hospital, Capital Medical University, Beijing
基金
中国博士后科学基金; 中国国家自然科学基金;
关键词
Biomarkers; CCR5; Integrated bioinformatics analysis; Primary Sjögren’s disease; T cells;
D O I
10.1007/s10067-025-07460-6
中图分类号
学科分类号
摘要
Objective: To identify and verify potential biomarkers for primary Sjögren’s disease (pSjD) using bioinformatics analysis and explore the molecular immune mechanisms of biomarkers.male-to-female ratio of 1:9 Methods: The pSjD datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differential expression analysis, weighted gene co-expression network analysis (WGCNA) and functional analysis were conducted. PPI network analysis was performed and the hub genes were screened by Cytoscape software. The diagnostic value was assessed by receiver operating characteristic (ROC) analysis. To explore biomarker-immune cell relations, we used CIBERSORT for cell-type identification, combined with scRNA-seq data. Lastly, we validated the expression of the biomarker in human samples. Results: A total of 96 overlapping genes, including 1 downregulated and 95 upregulated genes, were obtained. Based on the enrichment analysis, these overlapping genes were mapped to terms related to the functions and regulation of the immune system. CCR5 was identified as a critical biomarker and demonstrated high diagnostic accuracy for pSjD. From CIBERSORT analysis, CCR5 was significantly associated with diverse immune cells. Further scRNA-seq analysis indicated that CCR5 was specifically upregulated in T cells of pSjD salivary gland tissues, which was confirmed in pSjD patients. Conclusion: Our findings show the role of CCR5 in pSjD, mediated by immune mechanisms. CCR5 is localized in T cells of pSjD salivary glands. Elevated CCR5 expression may be a key biomarker, and increased CCR5 + T cells could aid future diagnosis, prognosis, and treatment of pSjD. © The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR) 2025.
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页码:2387 / 2401
页数:14
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共 63 条
  • [1] Mariette X., Criswell L.A., Primary Sjögren’s Syndrome, N Engl J Med, 378, pp. 931-939, (2018)
  • [2] Meijer J.M., Meiners P.M., Huddleston Slater J.J., Spijkervet F.K., Kallenberg C.G., Vissink A., Bootsma H., Health-related quality of life, employment and disability in patients with Sjogren’s syndrome, Rheumatology (Oxford), 48, pp. 1077-1082, (2009)
  • [3] Qin B., Wang J., Yang Z., Yang M., Ma N., Huang F., Zhong R., Epidemiology of primary Sjögren’s syndrome: a systematic review and meta-analysis, Ann Rheum Dis, 74, pp. 1983-1989, (2015)
  • [4] Thorlacius G.E., Bjork A., Wahren-Herlenius M., Genetics and epigenetics of primary Sjögren syndrome: implications for future therapies, Nat Rev Rheumatol, 19, pp. 288-306, (2023)
  • [5] Frank R., Hargreaves R., Clinical biomarkers in drug discovery and development, Nat Rev Drug Discov, 2, pp. 566-580, (2003)
  • [6] Firestein G.S., A biomarker by any other name, Nat Clin Pract Rheumatol, 2, (2006)
  • [7] Vijiaratnam N., Simuni T., Bandmann O., Morris H.R., Foltynie T., Progress towards therapies for disease modification in Parkinson’s disease, Lancet Neurol, 20, pp. 559-572, (2021)
  • [8] Therriault J., Schindler S.E., Salvado G., Pascoal T.A., Benedet A.L., Ashton N.J., Et al., Biomarker-based staging of Alzheimer disease: rationale and clinical applications, Nat Rev Neurol, 20, pp. 232-244, (2024)
  • [9] Yang S.R., Schultheis A.M., Yu H., Mandelker D., Ladanyi M., Buttner R., Precision medicine in non-small cell lung cancer: Current applications and future directions, Semin Cancer Biol, 84, pp. 184-198, (2022)
  • [10] Nunez J., de la Espriella R., Rossignol P., Voors A.A., Mullens W., Metra M., Et al., Congestion in heart failure: a circulating biomarker-based perspective. A review from the biomarkers working group of the heart failure association, european society of cardiology, Eur J Heart Fail, 24, pp. 1751-1766, (2022)