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2000
Volume 26, Issue 1
  • ISSN: 1871-5303
  • E-ISSN: 2212-3873
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Abstract

Introduction

This study investigated the association between cg11003133 DNA methylation and Rheumatoid Arthritis (RA), evaluating its diagnostic potential for RA and subtypes.

Methods

MethylTarget™ sequencing targeted cg11003133 (chr1:159076528-159076740) in RA, Ankylosing Spondylitis (AS), Psoriatic Arthritis (PsA), gout, Systemic Lupus Erythematosus (SLE), Dermatomyositis (DM), primary Sjögren's Syndrome (SS), and Healthy Controls (HC) patients. Logistic regression, random forest, and XGBoost models were applied, with Spearman’s correlation used to assess associations.

Results

RA and RF/CCP-positive patients showed significantly higher methylation at cg11003133_79/91 compared to HC and AS ( < 0.05), but lower levels compared to DM. Methylation at cg11003133_139 was elevated in RA compared to AS/SS ( = 0.04/0.03). Anti-TNF-α non-responders had higher cg11003133_79/91 methylation levels compared to HC/AS non-responders ( < 0.05). RF-negative RA patients had higher cg11003133_91 methylation than AS patients who failed anti-TNF-α treatment ( < 0.05). Haplotype CCCC correlated positively with CRP (r = 0.14, = 0.006); TTTT was significantly negatively correlated with erythrocyte sedimentation rate, CRP, and the presence of diabetes (r = -0.18, -0.15, and -0.14; < 0.001, 0.003, and 0.008, respectively). XGBoost and RF models achieved AUCs of 0.9911 and 0.9975 for RA non-RA, and 1 for RF/CCP double-negative double-positive RA.

Discussion

cg11003133 methylation is strongly linked to RA, aligning with its role in inflammasome activation. While promising for diagnostics, larger validation is needed.

Conclusions

cg11003133 methylation may serve as a diagnostic biomarker for RA and subtypes.

© 2026 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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/content/journals/emiddt/10.2174/0118715303401357250707080740
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Identifying AIM2 Circulating Methylation Levels as a Novel Diagnostic Biomarker for Rheumatoid Arthritis Using Targeted DNA Methylation Sequencing
Endocr Metab Immune Disord Drug Targets 26, E18715303401357 (2026); https://doi.org/10.2174/0118715303401357250707080740
/content/journals/emiddt/10.2174/0118715303401357250707080740
/content/journals/emiddt/10.2174/0118715303401357250707080740
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  • Article Type:     Research Article
Keyword(s): AIM2 protein; anti-TNF-α treatment; diabetes; DNA methylation; epigenesis; genetic; Rheumatoid arthritis

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