Unexpected Link Between Huntington’s Disease and Rheumatoid Arthritis Found in Study

Unexpected Link Between Huntington’s Disease and Rheumatoid Arthritis Found in Study

Genetic causes behind Huntington’s disease may overlap with those behind rheumatoid arthritis, an unexpected finding that could potentially open the door for new therapeutics targeting both diseases, a study suggests.

The study, “Comprehensive epigenetic landscape of rheumatoid arthritis fibroblast-like synoviocytes,” was published in the journal Nature Communications.

Rheumatoid arthritis is an aggressive autoimmune disease characterized by inflammation and destruction of the joints. Although therapies to treat the disease have improved, many patients still develop persistent inflammation and progressive disability.

Previous studies have suggested a role for epigenetic changes — external modifications to DNA to turn genes on or off that do not change the actual DNA sequence — in rheumatoid arthritis.

Researchers at the University of California San Diego School of Medicine and the Icahn School of Medicine at Mount Sinai studied the epigenome of cells from the joints of rheumatoid arthritis patients — called fibroblast-like synoviocytes — and compared them with the same type of cells obtained from patients with osteoarthritis, a disease resulting from the breakdown of joint cartilage.

They looked at several of the epigenetic modifications cells can have and generated 12 terabytes of data, which was analyzed using an algorithm they developed called EpiSig.

The analysis grouped the rheumatoid arthritis genome into 125 clusters based on epigenetic marks in multiple regulatory or functional elements.

Of these clusters, 13 were particularly enriched in these cells. Some of them were expected since they were related to immune responses, but other pathways “were totally unexpected, such as ‘Huntington’s Disease Signaling’ and a variety of others that still need to be explored,” the researchers wrote.

“We did not expect to find an overlap between rheumatoid arthritis and Huntington’s disease, 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,” Gary S. Firestein, MD, dean and associate vice chancellor of translational medicine at UC San Diego School of Medicine, said in a press release.

The team chose one specific target of the “Huntington’s disease signaling’” pathway, called Huntingtin-interacting protein-1 (HIP1), whose role was unknown in inflammatory diseases.

Depleting rheumatoid arthritis cells of HIP1 decreased their invasion capacities by nearly half, a property required by these cells to properly recover after cartilage and joint damage.

“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,” Firestein said.

“This methodology can also be used to find connections between other diseases, not just rheumatoid arthritis. As genes involved are discovered, researchers can potentially identify new treatment options and even repurpose existing drugs,” he said.

Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.
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Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.

3 comments

  1. Marge says:

    As a person living with RA I am very excited to see where this research is going to help me and others who are effected by both diseases.

  2. Becky Jarvis says:

    Hi there,
    I have an appointment tomorrow to see a Genetic Counsellor to determine whether or not I have Huntingdon’s. I’ve recently been diagnosed with chronic Arthritis. They’re saying its Polyarthralgia (general diagnosis which means they don’t actually know what I’ve got!) as it affects tons of joints.
    I suffer with depression and am on Fluoxatine.
    I’m fascinated by the recent(ish) discovery that Arthritis and Huntingdon’s may have a connection.
    I have a few symptoms of Lupus…raynauds and brittle hair and a history of anemia etc..but looking at symptoms on Google can often leave one convinced they’ll be dead by tomorrow so I’ve tried not to read too much into anything.
    Worse thing for me is being in ‘limbo!’ with these potential conditions…waiting for accurate diagnosis is torture and leaves ya chewing ya finger nails down to the bone.
    Oh well…be interesting to find out more.

  3. Nestor Corona says:

    My father died from huntington’s Disease, he was diagnosed back in 1970 at 35 and died in 2004 at 68, it all happened in Venezuela where the biggest HD affected and at risk community exist, from our experience and the immense love that we gave him I would like to recommend to all families and care givers the highest possible demonstration of love toward your patients as the most important ingredient, along of course with the appropriate treatment to improve their life quality, HD as any other disease, subjectively speaking, is more an opportunity embedded in an objective reality, to get the family closer to the fallen one who is actually sacrificing him/herself to unite them! After his passing we all felt a profound satisfaction for what we did in extending the life of our father who happened to outlived our mother by 10 years (She died from lung cancer, yes she was a smoker); our interpretation: She left because we needed to get closer to him as by that time we knew very little about his process, the way he behaved in the past and how it all affected us, I must publicly make a very special comment, on behalf of my family, to praise the help of Drs Margot DeYoung and Nancy Wexler for their infinite help, love and light given to us to better understand the disease! God bless them and their incredible team!

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