DNA methylation Linked to Autoantibody Production in Systemic Lupus Erythematosus

DNA methylation Linked to Autoantibody Production in Systemic Lupus Erythematosus
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In a new study entitled “Genome-Wide Assessment of Differential DNA Methylation Associated with Autoantibody Production in Systemic Lupus Erythematosus” researchers identified that epigenetic modifications in the DNA, specifically DNA methylation, is associated with autoantibody production in systemic lupus erythematosus. The study was published in the open-access journal PLOS One.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease  characterized by a hyper reactive immune system that mistakenly attacks healthy tissues. The key triggering mechanisms in SLE are the production of autoantibodies (i.e., directed against individuals’ own proteins). Notably, modifications in the DNA, particularly DNA methylation (the addition of a methyl group to specific nucleotides within the DNA chain) regulate gene expression, leading to a decrease or even silencing of a particular gene, a phenomenon previously linked to SLE. Since autoantibodies recognizing double-stranded DNA (dsDNA) are associated to and have a particular clinical relevance in SLE, the authors of this study determined whether DNA methylation impacts autoantibody production in SLE.

Researchers characterized the methylation landscape of 467,314 DNA sites in 326 women with SLE, who enrolled in the University of California, San Francisco Lupus Genetics Project. Additionally, researchers characterized the autoantibody status of the patients, either by reviewing their medical record and/or performing blood tests. Positive cases were considered if patients had at least one particular autoantibody identified, while negative cases were considered if all tests (medical record and blood test) came out negative for a specified autoantibody.

The results demonstrated that a methylation status occurring within eleven regions of patients’ DNA is significantly associated with anti-dsDNA autoantibody production. The team highlighted that not only is this the first large-scale study focusing on DNA methylation and autoantibody production in SLE, but it is also the first time specific genomic regions are associated with SLE- autoantibody production. In fact, only one gene (out of the eleven DNA regions) was previously linked to SLE susceptibility, thus suggesting that the differences in methylation associated with SLE autoantibody production are not associated with genetic variation within these regions.

The team emphasizes their findings support the rational that studying DNA methylation, together with other epigenetic modifications, is a complementary approach that will allow the identification and characterization of the biological pathways underlying SLE clinical heterogeneity.

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