The promise of precision medicine for rheumatoid arthritis

November 21, 2016
A hand affected by rheumatoid arthritis. Credit: James Heilman, MD/Wikipedia

In a new study, a Yale-led research team identified the mechanism of a gene that raises the risk of severe rheumatoid arthritis in susceptible individuals. The finding may lead to the development of treatment based on the genetic profiles of arthritis patients, the researchers said.

The study was published on Nov. 21 by Proceedings of the National Academy of Sciences (PNAS).

Rheumatoid arthritis is a common autoimmune disease that affects an estimated 3 million people and is most prevalent in women. The disease, which destroys cartilage in joints, can lead to severe disability. In its most severe form, vascular inflammation and internal organ damage occur, leading to premature death.

To understand the disease mechanism, Yale professor of medicine Richard Bucala, M.D., and his team focused on the disease-causing variants of the gene, MIF, which his lab had found to be associated with severe rheumatoid arthritis.

The research team conducted experiments with cells derived from the rheumatoid joint of patients who either had a disease-causing, high- expression variant of the MIF gene or a disease-protective, low-expression variant of the MIF gene. They found that high-expression MIF variants correlated with increased expression of the MIF receptor protein (CD44) and induced structural changes in the protein that occur in cancerous tissues. These cancerous properties in turn led to the destructive changes in the rheumatoid joint.

"We showed that the presence of the high-expression risk variant led to more MIF production and to structural alterations in a cell surface protein that had long been associated with invasive cancers," said Bucala. "The high-expression MIF risk gene helps explain the cancer-like properties of the rheumatoid joint."

This finding could lead to the application of MIF inhibitors, which the laboratory has developed for clinical testing in cancer and in autoimmunity, for severe in genetically susceptible patients. In the published study, the researchers used these drugs as well as new inhibitors to suppress the invasive effect of MIF on rheumatoid joint cells.

"It's a precision-medicine approach to treating autoimmune disease," Bucala noted. "Patients with a risk MIF genotype would be most effectively treated by such drugs."

Explore further: Study links mothers with rheumatoid arthritis and kids with epilepsy

More information: MIF allele-dependent regulation of the MIF coreceptor CD44 and role in rheumatoid arthritis, PNAS, www.pnas.org/cgi/doi/10.1073/pnas.1612717113

Related Stories

Study links mothers with rheumatoid arthritis and kids with epilepsy

November 16, 2016
A new study shows a link between mothers with rheumatoid arthritis and children with epilepsy. The study is published in the November 16, 2016, online issue of Neurology, a medical journal of the American Academy of Neurology. ...

Study pinpoints key genetic factor behind autoimmune diseases, cancer

January 13, 2016
Scientists have long known that variations in specific human genes are associated with distinct patterns of disease, but an understanding of the molecular mechanisms has remained elusive until now. A team of Yale researchers ...

Immunotherapy reduces cardiovascular risk in rheumatoid arthritis

July 9, 2016
Immunotherapy reduces cardiovascular risk in patients with rheumatoid arthritis, according to research presented today at Frontiers in CardioVascular Biology (FCVB) 2016 by Professor Aida Babaeva, head of the Department of ...

Compound in green tea found to block rheumatoid arthritis

February 16, 2016
Researchers at Washington State University in Spokane have identified a potential new approach to combating the joint pain, inflammation and tissue damage caused by rheumatoid arthritis.

Gene discoveries could help rheumatoid arthritis treatment

April 28, 2015
(HealthDay)—Genetic variations may hold clues to rheumatoid arthritis—suggesting not only who will develop the painful condition, but also predicting its severity and even who might die from it, a new study says.

Molecules involved in rheumatoid arthritis angiogenesis identified

May 16, 2014
Two protein molecules that fit together as lock and key seem to promote the abnormal formation of blood vessels in joints affected by rheumatoid arthritis, according to researchers at the University of Illinois at Chicago ...

Recommended for you

Fluid in the knee holds clues for why osteoarthritis is more common in females

June 26, 2017
Researchers have more evidence that males and females are different, this time in the fluid that helps protect the cartilage in their knee joints.

Biologics before triple therapy not cost effective for rheumatoid arthritis

May 29, 2017
Stepping up to biologic therapy when methotrexate monotherapy fails offers minimal incremental benefit over using a combination of drugs known as triple therapy, yet incurs large costs for treating rheumatoid arthritis (RA). ...

Drug for refractory psoriatic arthritis shows promise in clinical trial

May 24, 2017
In a pivotal phase-3 clinical trial led by a Stanford University School of Medicine investigator, patients with psoriatic arthritis for whom standard-of-care pharmaceutical treatments have provided no lasting relief experienced ...

Cross-species links identified for osteoarthritis

May 17, 2017
New research from the University of Liverpool, published today in the journal npj Systems Biology and Applications, has identified 'cell messages' that could help identify the early stages of osteoarthritis (OA).

Osteoarthritis could be prevented with good diet and exercise

May 12, 2017
Osteoarthritis can potentially be prevented with a good diet and regular exercise, a new expert review published in the Nature Reviews Rheumatology reports.

Rodents with trouble walking reveal potential treatment approach for most common joint disease

May 11, 2017
Maintaining the supply of a molecule that helps to nourish cartilage prevented osteoarthritis in animal models of the disease, according to a report published in Nature Communications online May 11.

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.