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

  • Systemic Lupus Erythematosus (G Tsokos, Section Editor)
  • Published:
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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 biomarkers. 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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Acknowledgments

This work was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number R01AI097134 and award number U19AI110502. M.T. is supported by the Instituto de Salud Carlos III from Spain through the Sara Borrell subprogram (CD13/00316).

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Authors and Affiliations

  1. Division of Rheumatology, University of Michigan, 5520 MSRB-1, SPC 5680, 1150 W. Medical Center Drive, Ann Arbor, MI, 48109, USA

    Maria Teruel & Amr H. Sawalha

  2. GENYO, Center for Genomics and Oncological Research Pfizer/University of Granada/Andalusian Regional Government, Avd de la Ilustración 114, 18016, Granada, Spain

    Maria Teruel

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  1. Maria Teruel
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Correspondence to Amr H. Sawalha.

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A.H.S. is listed as inventor on a patent application to use IFI44L methylation as a diagnostic test for lupus.

M.T. declares no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Systemic Lupus Erythematosus

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Teruel, M., Sawalha, A.H. Epigenetic Variability in Systemic Lupus Erythematosus: What We Learned from Genome-Wide DNA Methylation Studies. Curr Rheumatol Rep 19, 32 (2017). https://doi.org/10.1007/s11926-017-0657-5

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