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

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 system...

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Main Authors: 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
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Immunity, Inflammation and Disease
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Online Access:https://doi.org/10.1002/iid3.70128
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author 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
author_facet 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
author_sort Yiming Shi
collection DOAJ
description 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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spelling doaj-art-250bc82d3b2641e1ab89a059776f6a6b2025-02-06T07:50:38ZengWileyImmunity, Inflammation and Disease2050-45272025-01-01131n/an/a10.1002/iid3.70128Comparative Analysis of CXCR5 Circulating DNA Methylation Levels in Autoimmune Rheumatic DiseasesYiming Shi0Yingying Qin1Yunshen Li2Ping Jiang3Kai Wei4Jianan Zhao5Yu Shan6Yixin Zheng7Fuyu Zhao8Mi Zhou9Li Li10Yu Shen11Xinliang Lv12Yuejuan Zheng13Shicheng Guo14Qin Ding15Cen Chang16Dongyi He17Department of Rheumatology Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai ChinaDepartment of Rheumatology Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai ChinaDepartment of Rheumatology Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai ChinaDepartment of Rheumatology Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai ChinaDepartment of Rheumatology Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai ChinaDepartment of Rheumatology Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai ChinaDepartment of Rheumatology Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai ChinaDepartment of Rheumatology Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai ChinaDepartment of Rheumatology Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai ChinaDepartment of Rheumatology Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai ChinaInstitute of Arthritis Research in Integrative Medicine Shanghai Academy of Traditional Chinese Medicine Shanghai ChinaInstitute of Arthritis Research in Integrative Medicine Shanghai Academy of Traditional Chinese Medicine Shanghai ChinaTraditional Chinese Medicine Hospital of Inner Mongolia Autonomous Region Inner Mongolia Autonomous Region Hohhot ChinaThe Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity Shanghai University of Traditional Chinese Medicine Shanghai ChinaDepartment of Rheumatology Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai ChinaDepartment of Rheumatology Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai ChinaDepartment of Rheumatology Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai ChinaDepartment of Rheumatology Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai ChinaABSTRACT 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.https://doi.org/10.1002/iid3.70128autoimmune rheumatic diseasescirculating methylation levelsCXCR5DNA methylationinflammation
spellingShingle 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
Comparative Analysis of CXCR5 Circulating DNA Methylation Levels in Autoimmune Rheumatic Diseases
Immunity, Inflammation and Disease
autoimmune rheumatic diseases
circulating methylation levels
CXCR5
DNA methylation
inflammation
title Comparative Analysis of CXCR5 Circulating DNA Methylation Levels in Autoimmune Rheumatic Diseases
title_full Comparative Analysis of CXCR5 Circulating DNA Methylation Levels in Autoimmune Rheumatic Diseases
title_fullStr Comparative Analysis of CXCR5 Circulating DNA Methylation Levels in Autoimmune Rheumatic Diseases
title_full_unstemmed Comparative Analysis of CXCR5 Circulating DNA Methylation Levels in Autoimmune Rheumatic Diseases
title_short Comparative Analysis of CXCR5 Circulating DNA Methylation Levels in Autoimmune Rheumatic Diseases
title_sort comparative analysis of cxcr5 circulating dna methylation levels in autoimmune rheumatic diseases
topic autoimmune rheumatic diseases
circulating methylation levels
CXCR5
DNA methylation
inflammation
url https://doi.org/10.1002/iid3.70128
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