Epigenetic Variability in Systemic Lupus Erythematosus: What We Learned from Genome-Wide DNA Methylation Studies

Abstract

Purpose of Review DNA methylation has emerged as an important contributing factor in the pathogenesis of systemic lupus erythematosus (SLE). Here, we describe the DNA methylation patterns identified in SLE and how these epigenetic changes can influence disease susceptibility, clinical heterogeneity, and disease flares. Recent Findings Several genome-wide DNA methylation studies have been recently completed in SLE. Important observations include robust demethylation of interferon-regulated genes, which is consistent across all cell types studied to date, and is independent of disease activity. This interferon epigenetic signature was shown to precede interferon transcription signature in SLE, suggesting it might be an early event in the disease process. Recent studies also revealed DNA methylation changes specific for renal and skin involvement in SLE, providing a proof of principle for a value of DNA methylation studies in exploring mechanisms of specific disease manifestations, and potentially as prognostic bio-markers. Inherited ethnicity-specific DNA methylation patterns have also been shown to possibly contribute to differences in SLE susceptibility between populations. Finally, a recent study revealed that DNA methylation levels at IFI44L can accurately distinguish SLE patients from healthy controls, and from patients with other autoimmune diseases, promising to be the first epigenetic diagnostic marker for SLE. Summary Genome-wide DNA methylation studies in SLE have provided novel insights into disease pathogenesis, clinical heterogeneity, and disease flares. Further studies promise to reveal novel diagnostic, prognostic, and therapeutic targets for SLE.

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Epigenetic dysregulation of ACE2 and interferon-regulated genes might suggest increased COVID-19 susceptibility and severity in lupus patients

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