Comparative Analysis of CXCR5 Circulating DNA Methylation Levels in Autoimmune Rheumatic Diseases

IF 3.1 4区 医学 Q3 IMMUNOLOGY Immunity, Inflammation and Disease Pub Date : 2025-01-21 DOI:10.1002/iid3.70128
Yiming Shi, Yingying Qin, Yunshen Li, Ping Jiang, Kai Wei, Jianan Zhao, Yu Shan, Yixin Zheng, Fuyu Zhao, Mi Zhou, Li Li, Yu Shen, Xinliang Lv, Yuejuan Zheng, Shicheng Guo, Qin Ding, Cen Chang, Dongyi He
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Abstract

Objective

To assess CXC chemokine receptor 5 (CXCR5) circulating DNA methylation differences in autoimmune rheumatic diseases and their relation with clinical features.

Methods

Targeted methylation sequencing was performed using peripheral blood from 164 rheumatoid arthritis (RA), 30 systemic lupus erythematosus (SLE), 30 ankylosing spondylitis (AS), 30 psoriatic arthritis (PsA), 24 Sjögren's syndrome (SS) patients, and 30 healthy controls (HC).

Results

Significant differences in CXCR5 cg19599951 methylation were found between RA and HC, as well as AS and SLE. RA patients exhibited higher methylation than HC and AS (p < 0.01) but lower than SLE (p < 0.05). SLE patients showed higher methylation compared to HC, AS, and PsA (p < 0.001, 0.01, and 0.05, respectively). No significant differences were found in patients with SS compared to other autoimmune diseases and HC. Methylation at cg19599951_103 (r = 0.17, p < 0.05) and cg19599951_209 (r = 0.22, p < 0.01), along with the CC haplotype (r = 0.21, p < 0.01), showed significant positive correlations with erythrocyte sedimentation rate (ESR), while the CT (r = −0.27, p < 0.001) and TT haplotypes (r = −0.19, p < 0.05) were negatively correlated. For C-reactive protein (CRP), methylation at cg19599951_103 (r = 0.29, p < 0.001) and cg19599951_209 (r = 0.33, p < 0.0001), and the CC haplotype (r = 0.34, p < 0.0001) was positively correlated, whereas the CT (r = −0.36, p < 0.0001) and TT (r = −0.30, p < 0.0001) haplotypes were negatively correlated. Significant negative correlations were observed between the CT haplotype and rheumatoid factor (r = −0.25, p < 0.01), and anti-citrullinated protein antibody (r = −0.20, p < 0.05). No significant correlations were found in patients with SLE, AS, and SS. Receiver operating characteristic analysis showed CXCR5 methylation could classify patients with RA versus those with AS (AUC: 0.624−0.967).

Conclusion

Differential circulating CXCR5 methylation levels were observed in autoimmune rheumatic diseases, which correlated with inflammatory mediators in RA and may serve as potential biomarkers for RA diagnosis.

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自身免疫性风湿病中CXCR5循环DNA甲基化水平的比较分析
目的:探讨自身免疫性风湿病患者CXC趋化因子受体5 (CXCR5)循环DNA甲基化差异及其与临床特征的关系。方法:对164例类风湿性关节炎(RA)患者、30例系统性红斑狼疮(SLE)患者、30例强直性脊柱炎(AS)患者、30例银屑病关节炎(PsA)患者、24例Sjögren综合征(SS)患者和30例健康对照(HC)患者的外周血进行靶向甲基化测序。结果:CXCR5 cg19599951甲基化在RA和HC之间、as和SLE之间存在显著差异。结论:自身免疫性风湿病患者循环中CXCR5甲基化水平存在差异,与RA中的炎症介质相关,可能作为RA诊断的潜在生物标志物。
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来源期刊
Immunity, Inflammation and Disease
Immunity, Inflammation and Disease Medicine-Immunology and Allergy
CiteScore
3.60
自引率
0.00%
发文量
146
审稿时长
8 weeks
期刊介绍: Immunity, Inflammation and Disease is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research across the broad field of immunology. Immunity, Inflammation and Disease gives rapid consideration to papers in all areas of clinical and basic research. The journal is indexed in Medline and the Science Citation Index Expanded (part of Web of Science), among others. It welcomes original work that enhances the understanding of immunology in areas including: • cellular and molecular immunology • clinical immunology • allergy • immunochemistry • immunogenetics • immune signalling • immune development • imaging • mathematical modelling • autoimmunity • transplantation immunology • cancer immunology
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