自身免疫性风湿疾病中CXCR5循环DNA甲基化水平的比较分析

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

作者信息

Shi Yiming, Qin Yingying, Li Yunshen, Jiang Ping, Wei Kai, Zhao Jianan, Shan Yu, Zheng Yixin, Zhao Fuyu, Zhou Mi, Li Li, Shen Yu, Lv Xinliang, Zheng Yuejuan, Guo Shicheng, Ding Qin, Chang Cen, He Dongyi

机构信息

Department of Rheumatology, Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

出版信息

Immun Inflamm Dis. 2025 Jan;13(1):e70128. doi: 10.1002/iid3.70128.

DOI:10.1002/iid3.70128

PMID:39835879

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11748209/

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.

摘要

目的

评估自身免疫性风湿性疾病中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例类风湿关节炎（RA）、30例系统性红斑狼疮（SLE）、30例强直性脊柱炎（AS）、30例银屑病关节炎（PsA）、24例干燥综合征（SS）患者及30例健康对照（HC）的外周血进行靶向甲基化测序。

结果

发现RA与HC、AS与SLE之间CXCR5 cg19599951甲基化存在显著差异。RA患者甲基化水平高于HC和AS（p < 0.01），但低于SLE（p < 0.05）。与HC、AS和PsA相比，SLE患者甲基化水平更高（分别为p < 0.001、0.01和0.05）。与其他自身免疫性疾病及HC相比，SS患者未发现显著差异。cg19599951_103（r = 0.17，p < 0.05）和cg19599951_209（r = 0.22，p < 0.01）处的甲基化以及CC单倍型（r = 0.21，p < 0.01）与红细胞沉降率（ESR）呈显著正相关，而CT单倍型（r = -0.27，p < 0.001）和TT单倍型（r = -0.19，p < 0.05）呈负相关。对于C反应蛋白（CRP），cg19599951_103（r = 0.29，p < 0.001）和cg19599951_209（r = 0.33，p < 0.0001）处的甲基化以及CC单倍型（r = 0.34，p < 0.0001）呈正相关，而CT单倍型（r = -0.36，p < 0.0001）和TT单倍型（r = -0.30，p < 0.0001）呈负相关。CT单倍型与类风湿因子（r = -0.25，p < 0.01）及抗瓜氨酸化蛋白抗体（r = -0.20，p < 0.05）之间存在显著负相关。SLE、AS和SS患者未发现显著相关性。受试者工作特征分析显示，CXCR5甲基化可对RA患者与AS患者进行分类（曲线下面积：0.624 - 0.967）。