Upon unearthing rheumatoid arthritis’ epigenome, researchers at University of California San Diego School of Medicine and the Icahn School of Medicine at Mount Sinai have also discovered an overlap between the causes of rheumatoid arthritis and Huntington’s disease.
In a study recently published in Nature Communications, researchers at University of California San Diego School of Medicine and the Icahn School of Medicine at Mount Sinai have reportedly decoded the epigenetic blueprints for rheumatoid arthritis by utilizing new analytical tools.
Even more interesting though, upon unearthing rheumatoid arthritis’ epigenome, scientists also found an overlap between the causes of rheumatoid arthritis and Huntington’s disease.
Senior author Gary S. Firestein, MD, dean and associate vice chancellor of translational medicine at UC San Diego School of Medicine led the research team and was surprised by the team’s discovery. “We did not expect to find an overlap between rheumatoid arthritis and Huntington’s disease,” commented Dr Firestein in a recent statement, “but discovering the unexpected was the reason that we developed this technology. Now that we have uncovered this connection, we hope that it opens a door for treatment options for people living with either disease.”
The analytical tools used by the team exercised an investigative approach by composing an original algorithm named EpiSig, which incorporated and minimized the amount of epigenetic combinations in rheumatoid arthritis patients’ genes. As a result, the research team was able to pinpoint new cell signaling pathways.
“Comparing different types of epigenomic data is difficult because it involves a variety of different data subsets that cannot normally be analyzed together, including various methods in which DNA gets modified,” added Wei Wang, PhD, professor of chemistry, biochemistry and cellular and molecular medicine at UC San Diego School of Medicine. “This methodology can also be used to find connections between other diseases, not just rheumatoid arthritis,” added Firestein. “As genes involved are discovered, researchers can potentially identify new treatment options and even repurpose existing drugs.”
For the study, investigators evaluated the epigenome in cells from rheumatoid arthritis joints with osteoarthritis patients serving as the control group. Through an extensive process that evaluated chromatin, DNA, and histone modifications, both data sets were assessed.
Through the use of an original algorithm, the research team was also able to identify genomic areas with similar profiles. The study produced the first documented, comprehensive epigenomic expression of rheumatoid arthritis fibroblast-like synoviocytes (FLS), which included histone modifications (H3K27ac, H3K4me1, H3K4me3, H3K36me3, H3K27me3, and H3K9me3), open chromatin, RNA expression, and whole-genome DNA methylation.
By displaying that Huntingtin-interacting protein-1 regulates FLS invasion into matrix, the relevance of “Huntington’s Disease Signaling” was validated. Essentially, a high-resolution epigenomic landscape of rheumatoid arthritis and a demonstration of the potential for integrative analyses to pinpoint unanticipated therapeutic targets were established by the study.
“By revealing the comprehensive epigenetics behind rheumatoid arthritis, we now have a better understanding of this disease. More importantly, our new approach, could not only help patients with rheumatoid arthritis, but also people with other immune-mediated diseases,” Dr Firestein said.
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