ArticleArthritis & rheumatology (Hoboken, N.J.)2026
DNA Methylation Profiling Reveals Distinct Epigenetic Clusters and Suggests Epigenetic Patterns Associated With Sex and Disease Activity in Childhood-Onset Lupus.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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Who cites it
2 citing papers in PubMed.
- Circulating cell-free DNA as a biomarker in systemic lupus erythematosus: A narrative review.Journal of translational autoimmunity · 2026Review
- Methylation and polygenic risk scores capture different features of Systemic Lupus Erythematosus.Rheumatology (Oxford, England) · 2026Article
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14 authors.
Funding
Abstract
objectiveSystemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple organs, with childhood-onset SLE (cSLE) typically presenting a more severe course and greater genetic risk than adult-onset SLE. Although DNA methylation plays a key role in lupus pathogenesis, the epigenetic landscape of cSLE remains understudied. This study aimed to investigate DNA methylation changes in cSLE.
methodsA total of 64 patients with cSLE and 47 healthy control DNA samples isolated from peripheral blood mononuclear cells (PBMCs), along with an independent validation cohort of 38 patient DNA samples from whole blood, were analyzed. DNA methylation was assessed using the Infinium MethylationEPIC version 2.0 array. Methylation differences were tested via linear regression adjusting for age, sex, medication use, and cell composition. Clinical features were compared using the chi-square test or Fisher's exact test, and Gene Ontology enrichment was conducted.
resultsDifferential methylation analysis revealed significant hypomethylation in interferon-regulated genes (eg, DTX3L, PARP9, IFI44L, MX1), enriched in type I interferon-related processes. Hypomethylation in genes linked to B cell activation and senescence correlated with higher SLE Disease Activity Index scores. K-means clustering identified three distinct methylation-based cSLE subgroups, each enriched for different biologic processes: cell adhesion and growth factor response (cluster 1), cell differentiation and fate (cluster 2), and oxidative stress and Ras-associated protein-1 signaling (cluster 3). Sex-based analysis showed immune-related hypomethylation in male patients, with almost 90% of these sites identified in PBMCs also replicating in an independent whole blood dataset.
conclusioncSLE displays distinct DNA methylation patterns associated with disease activity, molecular subgroups, and sex, underscoring the potential for epigenetically informed diagnostics and therapies.
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