Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Immun Inflamm Dis. 2023 Jun;11(6):e902. doi: 10.1002/iid3.902.
To assess the differences in circulating DNA methylation levels of CXCR5 between rheumatoid arthritis (RA) and osteoarthritis (OA) and healthy controls (HC), and the correlation of methylation changes with clinical characteristics of RA patients.
Peripheral blood samples were collected from 239 RA patients, 30 patients with OA, and 29 HC. Target region methylation sequencing to the promoter region of CXCR5 was achieved using MethylTarget. The methylation level of cg04537602 and methylation haplotype were compared among the three groups, and the correlation between methylation levels and clinical characteristics of RA patients was performed by Spearman's rank correlation analysis.
The methylation level of cg04537602 was significantly higher in the peripheral blood of RA patients compared with OA patients (p = 1.3 × 10 ) and in the HC group (p = 5.5 × 10 ). The sensitivity was enhanced when CXCR5 methylation level combined with rheumatoid factor and anti-cyclic citrullinated peptide with area under curve (AUC) of 0.982 (95% confidence interval 0.970-0.995). The methylation level of cg04537602 in RA was positively correlated with C-reactive protein (CRP) (r = .16, p = .01), and in RA patients aged 60 years and above, cg04537602 methylation levels were positively correlated with CRP (r = .31, p = 4.7 × 10 ), tender joint count (r = .21, p = .02), visual analog scales score (r = .21, p = .02), Disease Activity Score in 28 joints (DAS28) using the CRP level DAS28-CRP (r = .27, p = 2.1 × 10 ), and DAS28-ESR (r = .22, p = .01). We also observed significant differences of DNA methylation haplotypes in RA patients compared with OA patients and HC, which was consistent with single-loci-based CpG methylation measurement.
The methylation level of CXCR5 was significantly higher in RA patients than in OA and HC, and correlated with the level of inflammation in RA patients, our study establishes a link between CXCR5 DNA methylation and clinical features that may help in the diagnosis and disease management of RA patients.
评估 CXCR5 循环 DNA 甲基化水平在类风湿关节炎（RA）、骨关节炎（OA）和健康对照（HC）之间的差异，以及甲基化变化与 RA 患者临床特征的相关性。
收集 239 例 RA 患者、30 例 OA 患者和 29 例 HC 的外周血样本。采用 MethylTarget 对 CXCR5 启动子区域进行靶向区域甲基化测序。比较三组之间 cg04537602 的甲基化水平和甲基化单倍型，并采用 Spearman 秩相关分析评估甲基化水平与 RA 患者临床特征的相关性。
与 OA 患者（p=1.3×10-3）和 HC 组（p=5.5×10-5）相比，RA 患者外周血中 cg04537602 的甲基化水平显著升高。当 CXCR5 甲基化水平与类风湿因子和抗环瓜氨酸肽联合使用时，曲线下面积（AUC）为 0.982（95%置信区间 0.970-0.995），灵敏度增强。RA 患者的 cg04537602 甲基化水平与 C 反应蛋白（CRP）呈正相关（r=0.16，p=0.01），在 60 岁及以上的 RA 患者中，cg04537602 甲基化水平与 CRP 呈正相关（r=0.31，p=4.7×10-3），与压痛关节数（r=0.21，p=0.02）、视觉模拟量表评分（r=0.21，p=0.02）、基于 CRP 水平的 28 关节疾病活动度评分（DAS28-CRP）（r=0.27，p=2.1×10-3）和基于 ESR 的 DAS28（r=0.22，p=0.01）。我们还观察到 RA 患者与 OA 患者和 HC 患者之间 CXCR5 基因的 DNA 甲基化单倍型存在显著差异，这与基于单 CpG 甲基化测量的结果一致。
RA 患者的 CXCR5 甲基化水平明显高于 OA 和 HC，与 RA 患者的炎症水平相关，本研究建立了 CXCR5 DNA 甲基化与临床特征之间的联系，这可能有助于 RA 患者的诊断和疾病管理。
