Joint resolution: A link between Huntington's disease and rheumatoid arthritis

May 15, 2018, University of California - San Diego
Joint resolution: A link between Huntington's disease and rheumatoid arthritis
Gary Firestein, MD, dean and associate vice chancellor of translational medicine at UC San Diego School of Medicine. Credit: UC San Diego Health

Using new analytic tools, researchers at University of California San Diego School of Medicine and the Icahn School of Medicine at Mount Sinai have decoded the epigenetic landscape for rheumatoid arthritis (RA), a common autoimmune disease that affects more than 1.3 million Americans. In unveiling RA's epigenome—the proteins and molecules that decorate DNA and help turn genes on and off—scientists made a surprising discovery: an overlap between the causes of RA and Huntington's disease, a fatal and incurable genetic brain disease.

The findings are published online in the May 15 issue of Nature Communications.

The research team, led by senior author Gary S. Firestein, MD, dean and associate vice chancellor of translational at UC San Diego School of Medicine, said the unexpected connection between RA and Huntington's disease opens up the possibility of new therapeutic targets and drugs for both conditions.

"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," said Firestein.

RA is a that causes pain and swelling in joints. As an autoimmune disease, it can also affect other organs, including heart and blood vessels. Treatment for RA has improved, but 10 to 20 percent of patients do not respond to any available medicines.

The investigative approach used by the research team involved developing a novel algorithm, or set of computational rules, called EpiSig, which integrated and reduced the number of epigenetic combinations in the genes of patients with RA. The team could then identify 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," said Wei Wang, Ph.D., 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 and even repurpose existing drugs."

Firestein and team studied the epigenome in cells from the joints of patients with RA. Patients with osteoarthritis, which is a disease of cartilage degeneration, served as a control group. Both data sets were analyzed through an expansive process that examines chromatin, DNA and histone modifications. The results produced 12 terabytes of data (12 trillion bytes) that were then analyzed using EpiSig.

Epigenetics, or "above the genome", is the study of processes that alter the gene structure without changing the DNA sequence itself. These DNA modifications are essential to human growth and development and change throughout people's lives. Epigenetic changes are influenced by a variety of environmental factors, including stress, activity and lifestyle choices.

"By revealing the comprehensive epigenetics behind rheumatoid arthritis, we now have a better understanding of this . More importantly, our new approach, could not only help patients with , but also people with other immune-mediated diseases," Firestein said.

Explore further: Epigenetics alters genes in rheumatoid arthritis

More information: Rizi Ai et al, Comprehensive epigenetic landscape of rheumatoid arthritis fibroblast-like synoviocytes, Nature Communications (2018). DOI: 10.1038/s41467-018-04310-9

Related Stories

Epigenetics alters genes in rheumatoid arthritis

July 3, 2012
It's not just our DNA that makes us susceptible to disease and influences its impact and outcome. Scientists are beginning to realize more and more that important changes in genes that are unrelated to changes in the DNA ...

Study finds bacteria in milk linked to rheumatoid arthritis

January 30, 2018
A strain of bacteria commonly found in milk and beef may be a trigger for developing rheumatoid arthritis in people who are genetically at risk, according to a new study from the University of Central Florida.

Rheumatoid arthritis meets precision medicine

March 19, 2018
Scientists are bringing precision medicine to rheumatoid arthritis for the first time by using genetic profiling of joint tissue to see which drugs will work for which patients, reports a new Northwestern Medicine multi-site ...

Gene expression study may help guide Arthritis care

February 22, 2018
Researchers who analyzed gene expression in synovial tissue samples from rheumatoid arthritis patients' joints identified different patterns that may be clinically meaningful. The findings, which are published in Arthritis ...

Maintaining sufficient vitamin D levels may help to prevent rheumatoid arthritis

November 20, 2017
Maintaining sufficient vitamin D levels may help to prevent the onset of inflammatory diseases like rheumatoid arthritis, research led by the University of Birmingham has discovered.

Recommended for you

Aggression neurons identified

May 25, 2018
High activity in a relatively poorly studied group of brain cells can be linked to aggressive behaviour in mice, a new study from Karolinska Institutet in Sweden shows. Using optogenetic techniques, the researchers were able ...

The brain's frontal lobe could be involved in chronic pain, according to research

May 25, 2018
A University of Toronto scientist has discovered the brain's frontal lobe is involved in pain transmission to the spine. If his findings in animals bear out in people, the discovery could lead to a new class of non-addictive ...

Doctors fail to flag concussion patients for critical follow-up

May 25, 2018
As evidence builds of more long-term effects linked to concussion, a nationwide study led by scientists at UCSF and the University of Southern California has found that more than half of the patients seen at top-level trauma ...

Bursts of brain activity linked to memory reactivation

May 24, 2018
Leading theories propose that sleep presents an opportune time for important, new memories to become stabilized. And it's long been known which brain waves are produced during sleep. But in a new study, researchers set out ...

Study suggests brainwave link between disparate disorders

May 24, 2018
A brainwave abnormality could be a common link between Parkinson's disease, neuropathic pain, tinnitus and depression—a link that authors of a new study suggest could lead to treatment for all four conditions.

Researchers define molecular basis to explain link between a pregnant mother's nutrition and infant growth

May 24, 2018
For years, pregnant mothers have questioned their nutritional habits: "Will eating more cause my baby to be overweight?" Or, "I'm eating for two, so it won't hurt to have an extra serving, right?"

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.