Changes in DNA methylation are associated with systemic lupus erythematosus flare remission and clinical subtypes

作者：Mary K. Horton, Joanne Nititham, Kimberly E. Taylor, Patricia Katz, Chun Jimmie Ye, Jinoos Yazdany, Maria Dall’Era, Charlotte Hurabielle, Lisa F. Barcellos, Lindsey A. Criswell, Cristina M. Lanata · 发表于：Clinical Epigenetics · 年份：2024 · DOI：10.1186/s13148-024-01792-x · 被引用次数：11 · 研究领域：Systemic Lupus Erythematosus Research、Systemic Sclerosis and Related Diseases、interferon and immune responses

BACKGROUND: Systemic lupus erythematosus (SLE) has numerous symptoms across organs and an unpredictable flare-remittance pattern. This has made it challenging to understand drivers of long-term SLE outcomes. Our objective was to identify whether changes in DNA methylation over time, in an actively flaring SLE cohort, were associated with remission and whether these changes meaningfully subtype SLE patients. METHODS: Fifty-nine multi-ethnic SLE patients had clinical visits and DNA methylation profiles at a flare and approximately 3 months later. Methylation was measured using the Illumina EPIC array. We identified sites where methylation change between visits was associated with remission at the follow-up visit using limma package and a time x remission interaction term. Models adjusted for batch, age at diagnosis, time between visits, age at flare, sex, medications, and cell-type proportions. Separately, a paired T-test identified Bonferroni significant methylation sites with ≥ 3% change between visits (n = 546). Methylation changes at these sites were used for unsupervised consensus hierarchical clustering. Associations between clusters and patient features were assessed. RESULTS: Nineteen patients fully remitted at the follow-up visit. For 1,953 CpG sites, methylation changed differently for remitters vs. non-remitters (Bonferroni p < 0.05). Nearly half were within genes regulated by interferon. The largest effect was at cg22873177; on average, remitters had 23% decreased m...