A whole genome methylation analysis of systemic lupus erythematosus: hypomethylation of the IL10 and IL1R2 promoters is associated with disease activity

Abstract

The etiology of systemic lupus erythematosus (SLE) involves a complex interaction of genetic and environmental factors. Investigations have shown that environmentally driven epigenetic changes contribute to the etiology of SLE. Here, we hypothesize that aberrant DNA methylation may contribute to the activation of the immune machinery and trigger lupus disease activity. A whole genome methylation array was applied to investigate the DNA methylation changes between 12 pairs of active SLE patients and healthy controls. The results were further confirmed in 66 SLE patients, 102 healthy controls. The methylation statuses of the IL10 and IL1R2 genes were significantly reduced in the SLE patient samples relative to the healthy controls (age-adjusted odds ratios, 64.2 and 16.9, respectively, Po0.0001). There was a trend toward SLE patients having hypomethylated IL10 and IL1R2 genes accompanied by greater disease activity. We observed that the methylation degree of IL10 and IL1R2 genes were reduced in the rheumatoid arthritis (RA) patients as well but the hypomethylation change was more significant in IL1R2 genes than in the IL10 genes in RA patients. This study demonstrated that DNA hypomethylation might be associated with SLE. Hypomethylated IL10 and IL1R2 genes may provide potential epigenetic markers as clinical predictors for autoimmune diseases.

Interleukin-1 Receptor Type 2 Acts with c-Fos to Enhance the Expression of Interleukin-6 and Vascular Endothelial Growth Factor A in Colon Cancer Cells and Induce Angiogenesis

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Aberrant promoter methylation of the CD4 gene in peripheral blood cells of mastitic dairy cows

“…To date, comparison of the divergence of DNA methylation in whole blood between cases and controls of common diseases has been well documented (Nadeau et al, 2010;Chowdhury et al, 2011;Toperoff et al, 2011;Lin et al, 2012). However, whole blood consists of many functionally and developmentally distinct cell populations in varying proportions.…”

IL-1 Receptor Type 2 Suppresses Collagen-Induced Arthritis by Inhibiting IL-1 Signal on Macrophages

“…Studies using animal models demonstrated that IL-1 is involved in the development of RA (18,19), and blockade of IL-1 signaling is effective in treating RA (20)(21)(22)(23), although this cytokine is primarily important in the development of autoinflammatory diseases, such as Familial Mediterranean fever, cryopyrin-associated periodic syndromesa, and Still's disease (19,24,25). Because the concentration of IL-1R2 protein is increased in the synovial fluid (26) and plasma (27,28) of RA patients, and the promoter region of the IL1R2 gene is hypomethylated in PBMCs of RA patients (28), IL-1R2 is suggested to be involved in its pathogenesis.…”