Study Links Rheumatoid Arthritis and Huntington’s Disease

Rheumatoid arthritis (RA) is a chronic autoimmune disorder the primarily affects the joints, triggering symptoms such as joint pain, swelling, and stiffness – which can vary from mild to severe. The damage to the joints that is caused by RA usually occurs on both sides of the body. Although it remains unknown as to what causes the disorder, there is some evidence that suggests RA could be hereditary.

Huntington’s disease is a progressive brain disorder that leads to muscle problems, involuntary movements, impaired gait, loss of cognitive ability, as well as emotional problems. It is caused by a defect in a single gene that leads to damage in certain areas of the brain. This means that if a parent has Huntington’s disease, there is a 50% chance that their child will inherit the disorder.

Apart from symptoms such as muscle stiffness and depression, these two disorders have no known similarities between them.

That is, until now, when Researchers from the San Diego School of Medicine at the University of California and from the Icahn School of Medicine at Mount Sinai made an unexpected discovery - a genetic link between RA and Huntington’s disease.

Hidden in the epigenome

Using the latest analytical tools, the research team was deciphering the embryonic development of RA when they came across a link in the epigenome between the causes of RA and Huntington’s disease. The epigenome is comprised of proteins and molecules that attach to DNA and help to turn genes on and off. They developed an algorithm called EpiSig, which helped to integrate and diminish the number of epigenetic combinations in the genes of patients with RA. 

They then studied the epigenome from the joints of patients with RA, known as fibroblast-like synoviocytes, and compared them with the same cells from patients with osteoarthritis (the control group). “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,” said Dr. Gary S. Firestein, dean and associate vice chancellor of translational medicine at UC San Diego School of Medicine.

The potential for new therapeutic approaches 

The researchers grouped the RA genome into 125 clusters, based on epigenetic changes – which are changes that are influenced by a wide range of environmental factors, including stress, activity, and lifestyle choices. “There is a genetic code that will tell you what the protein structures are going to be, which then determines many aspects of your human physiology such as height, eye color, hair color. Epigenetics are a series of molecules that don’t change that genetic code but are responsible for deciding which genes are turned on and when,” said Dr. Firestein.

Read on to learn more about the strange connection between RA and Huntington's disease.