Identifying AIM2 Circulating Methylation Levels as a Novel Diagnostic Biomarker for Rheumatoid Arthritis Using Targeted DNA Methylation Sequencing

作者：Jianan Zhao, B. He, Yu Shan, Kai Wei, Ping Jiang, Yiming Shi, Cen Chang, Yixin Zheng, Fuyu Zhao, Yunshen Li, Yuejuan Zheng, Yehua Jin, Xinliang Lv, Mengru Guo · 发表于：Endocrine Metabolic & Immune Disorders - Drug Targets · 年份：2025 · DOI：10.2174/0118715303401357250707080740 · 被引用次数：3 · 研究领域：Rheumatoid Arthritis Research and Therapies、Spondyloarthritis Studies and Treatments、Systemic Sclerosis and Related Diseases

INTRODUCTION: cg11003133 DNA methylation and Rheumatoid Arthritis (RA), evaluating its diagnostic potential for RA and subtypes. METHODS: 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 (FDR < 0.05), but lower levels compared to DM. Methylation at cg11003133_139 was elevated in RA compared to AS/SS (FDR = 0.04/0.03). Anti- TNF-α non-responders had higher cg11003133_79/91 methylation levels compared to HC/AS non-responders (FDR < 0.05). RF-negative RA patients had higher cg11003133_91 methylation than AS patients who failed anti-TNF-α treatment (FDR < 0.05). Haplotype CCCC correlated positively with CRP (r = 0.14, P = 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; P < 0.001, 0.003, and 0.008, respectively). XGBoost and RF models achieved AUCs of 0.9911 and 0.9975 for RA versus non-RA, and 1 for RF/CCP double-negative versus double-positive RA. DISCUSSION: cg11003133 methylation is strongly linked to RA, aligning with its role in inflammasome act...