Genomic study: Why children in remission from rheumatoid arthritis experience recurrences

August 29, 2013

More children with juvenile rheumatoid arthritis are experiencing remission of their symptoms, thanks to new biological therapies, but the remission is not well-understood. A new study published today in Arthritis Research & Therapy provides the first genomic characterization of remission in juvenile rheumatoid arthritis patients.

"It turns out that even though these children in remission appear to be perfectly normal and symptom-free, their immune systems are still perturbed," says James N. Jarvis, MD, clinical professor of pediatrics in the University at Buffalo School of Medicine and Biomedical Sciences and the study's lead author.

The study notes that 35-50 percent of children with juvenile rheumatoid arthritis achieve remission while being treated with the standard treatments, methotrexate or methotrexate in combination with biopharmaceuticals.

"Our study provides some insight into why so many children in remission experience disease flares even when their disease has been stable for weeks or months, and why 50 percent of children who try to come off medication experience disease flares within two to six months," Jarvis says.

The research was conducted at the University of Oklahoma Health Sciences Center by Jarvis and co-authors, and was supported by the National Institutes of Health, the Oklahoma Center for the Advancement of Science and Technology and the Arthritis Foundation, which continues to fund Jarvis' research in this area. Some members of the team, including Jarvis, now work at UB's Clinical and Translational Research Center (CTRC).

The study compared profiles from two independent cohorts of 14 patients each, all in remission from juvenile rheumatoid arthritis, to those of 15 healthy controls. The patients were on two different medication regimens. Patients were followed every two to three months for at least a year.

"Remission, of course, is our goal," says Jarvis. "I like to say it's hard to get somewhere when you don't know where 'somewhere' is. My lab is trying to build a 'genomic roadmap' for what remission is and exactly how we get there. That way, we can find a way to get these children into remission more quickly and for longer periods."

The new study confirms preliminary research by Jarvis, suggesting that remission experienced by patients with juvenile rheumatoid arthritis on medication is not a "return to normal" but is, instead, a distinct biologic state. The study finds that this distinct biologic state results from pro-inflammatory responses being counter-balanced by anti-inflammatory responses caused by gene expression changes that medication induces.

A key finding is that in these patients depends on HNF4a, a transcription factor that binds to DNA, acting as an "on" or "off" switch for gene expression. Until now, Jarvis says, HNF4a was seen only as a regulator of metabolism in liver and pancreatic cells.

"Our research suggests that HNF4a is one of what we suspect is a group of master switches that regulate therapeutic response," explains Jarvis.

The study found that more than 200 genes in white blood cells were expressed differently in taking a combination treatment of methotrexate and a biological drug called etanercept compared to healthy controls. Some of those differentially expressed genes have been shown to bind to HNF4a.

Jarvis notes that the findings will make possible future studies that will identify specific biomarkers involved in how individual patients respond to specific therapies.

"This is a first step toward the goal of identifying biomarkers that will ultimately allow clinicians to personalize treatment by predicting which will respond best to which therapies," he says.

He adds that this kind of research will depend on longitudinal studies that monitor gene expression before, during and after treatment. Jarvis currently is principal investigator on a $1.2 million NIH grant to study microarray-based biomarkers in juvenile idiopathic . He also is studying the role of epigenetics in juvenile supported by several foundation grants.

Explore further: New rheumatoid arthritis treatment shown to be effective: Half of all patients symptom-free within six months

Related Stories

New rheumatoid arthritis treatment shown to be effective: Half of all patients symptom-free within six months

December 11, 2012
Rheumatoid arthritis is a chronic disease characterized by inflammation of the joints. A rapid suppression of inflammation is important for a good prognosis. Marloes Vermeer, a PhD student at the University of Twente, investigated ...

Obesity is a risk factor for poor remission rates in RA

July 6, 2012
(HealthDay) -- For patients with long-standing rheumatoid arthritis treated with anti-tumor necrosis factor-α (anti-TNFα) therapies, obesity is related to poor remission rates, according to a study published online ...

Study finds potential markers for severity of childhood arthritis

July 12, 2013
(Medical Xpress)—Children who suffer from arthritis could one day receive more targeted treatment thanks to potential markers for the severity of the disorder discovered by researchers at the University of Adelaide and ...

Overweight and obese patients less likely to achieve remission in early RA

June 14, 2013
A new study presented today at EULAR 2013, the Annual Congress of the European League Against Rheumatism, shows that overweight and obese patients are less likely to achieve successful remission in early rheumatoid arthritis ...

New rheumatoid arthritis treatment moves a step closer to reality

August 15, 2013
A new rheumatoid arthritis treatment has moved a step closer to reality with the announcement of collaboration between a University of Queensland start-up company and a major pharmaceutical firm.

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.