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New Study: Different RA Joints May Have Unique Genetic Markers

Ever wonder why the RA drugs you take only seem to affect certain joints? Or why the drugs might be literally life-changing to one person with rheumatoid disease, but have little or no affect on another?

Scientists are now a step closer to the answer.

According to a recent article published in NIH News in Health, the monthly newsletter from the National Institutes of Health, a new scientific study shows that knee and hip joints affected by rheumatoid arthritis seem to have different genetic markers linked to inflammation.

The new findings, published in the professional journal Nature Communications in early June, suggest that different joints may have varying disease mechanisms. The findings may lead to more effective, personalized therapies for treating the disease in the future.

Researchers have known for some time that the unique chemical tags found in different joints that trigger inflammation, called epigenetic markers, differ between RA and osteoarthritis. But in this study, researchers looked at epigenetic patterns in joint cells from 30 people with RA and 16 with osteoarthritis. They found what they expected to find in the RA and OA joints, but were surprised to discover that the epigenetic markers also differed between the hip and knee joints in the patients with rheumatoid arthritis.

From the article: “The scientists next assessed the affected biological pathways that distinguish different joints. Knee and hip joints with rheumatoid arthritis had differing activated genes and biological pathways. Many of these pathways were related to immune system function.”

They also found that new drugs that treat RA may affect some of those pathways. That finding may mean an opportunity to treat different arthritic joints with more precise approaches in the future. “We showed that the epigenetic marks vary from joint to joint in rheumatoid arthritis,” said study coauthor Dr. Gary S. Firestein of the University of California, San Diego. “This might provide an explanation as to why some joints improve while others do not, even though they are exposed to the same drug.”

This was a very small study, and more in depth, targeted studies will likely be carried out in the future. Still, the scientists’ findings here offer a lot of hope for those of us who live each day with the symptoms and joint destruction so characteristic of rheumatoid disease. Perhaps one day treatments will be much better than they are today.

Maybe they’ll even find a cure.

This article represents the opinions, thoughts, and experiences of the author; none of this content has been paid for by any advertiser. The team does not recommend or endorse any products or treatments discussed herein. Learn more about how we maintain editorial integrity here.

  1. Arthritis Mechanisms May Vary by Joint. (2016, August) National Institutes of Health. Retrieved on August 4, 2016 from
  2. Ai, R., et al. Joint-specific DNA methylation and transcriptome signatures in rheumatoid arthritis identify distinct pathogenic processes. (2016, June10) Nature Communications. Retrieved on August 4, 2016 from


  • Connie Rifenburg
    3 years ago

    Hello Wren, Thanks for this article. I was wondering whether our group has ever done a questionnaire about how many people have RA AND OA? How common is it to have both?

    In my case, my RA showed up in 2003 – almost textbook – high RF numbers and equally effecting both sides of my body. Sometime around 2009, my OA took a front seat as my finger joints became deformed significantly. The first joint below my fingernails, and my wrist/thumb and toe joints are also showing significant swelling, deformity and pain.

    After experiencing increasing pain in my knees I had xrays recently and they found that my Rknee is bone on bone and full of OA in all 3 compartments. My Lknee is the same, but only involving 1 compartment.

    I have also lost 2 inches in height just in the last 2 yrs. I have measured 5’6″ since highschool, and last year I was measured at 5’4.5″ for the first time and just this past week I was measured at 5’4″ (another 1/2″ shorter)I show increasing amounts of OA in my spine also. It just seems to me that my RA is less significant now than my OA and yet my dr. said the treatment is the same for both.

    When my RA was in a 2-yr flare, the effects of the RA included my organs; Heart, lungs, stomach, the cartilage surrounding my breast bone was inflamed and tendons in my shoulder and legs spontaneously tore. When we finally got the right meds treating the RA, those things resolved over a few years. Now, I don’t have the organ involvement, but the OA seems to be progressing faster than the RA symptoms did and I see the joints deforming more and more and limiting my movements.

    I scheduled surgery on my left wrist and thumb/tendon for Aug 3rd, but 1 wk before I was to have it, I came down with bacterial pneumonia in one lung so all was stopped until this week, where I am feeling better and will now reschedule the repair of the damage from OA in my left wrist. I’m told it’s 6-8wks recovery. I have lost almost all feeling in my fingertips on my left hand from carpal tunnel too.

    After reading your article, it occurred to me that maybe it was common to have both RA and OA and wondered whether people had relief of the OA with the same medications as used for their RA? (that hasn’t been the case with me)

    Thanks again for the information on possible future treatment targeting our DNA individually. There must be some hope out there.

  • Wren moderator author
    3 years ago

    Hi, Connie!

    Thank you for taking the time to write such a detailed comment! You must be incredibly strong–not to mention courageous!–to cope so well with both RD and osteoarthritis. I’m glad to hear that your rheumatologist was able to help you find the right combo of drugs to slow it down and relieve your RD symptoms.

    But oh my, it does sound like osteoarthritis is the bigger culprit for you! It can definitely cause the kind of bone changes you mention. I hope that your upcoming wrist surgery goes well and relieves your pain.

    You might want to get your bone density checked, as well. Osteoporosis causes the bones to become light and fragile, and in the spine they may slowly break down and compress, causing a loss of height. And of course, it can make make your other bones very fragile, especially your wrists and hips. Your rheumatologist or PCP should be able to get you a bone density scan to help with a diagnosis of osteoporosis. I hope you don’t have it, but it’s also common in people who have RD, especially in post-menopausal women.

    As you may know, RD generally affects people between the ages of 30 and 60, with it becoming more likely as we age, though the cause is still unknown. (It can, of course, affect people both younger and older; children as young as infants get RD). RD is an autoimmune disease and is often difficult to treat, since it can affect each patient just a little bit differently. Not only do the degree of pain and other symptoms vary from person to person, but also how each treatment works. What works for you may not work for me, and vice versa. And, the drugs that treat RD may work for a while, then stop as the body’s immune system figures out how to get around it.

    On the other hand, osteoarthritis is a disease most often associated with age; it’s known as the “wear and tear” arthritis. The cartilage between the bones of the joint slowly disintegrates, and this can start anywhere from a person’s 30s to their 80s and beyond.

    The only drugs I’m aware of that treat both RD and OA are NSAIDs–acetaminophen, ibuprofen, naproxyn, etc. These drugs work to decrease inflammation (and with it, pain), which is common in both RD and OA. The difference is that in RD, the inflammation is systemic; in OA, it’s concentrated in the areas around the affected joints.

    I guess what I’m working around to here is YES–it’s pretty common for people who have RD to have OA as well, depending on their age. Like you, I have both, but for me, the OA is still mostly confined to my fingertips. My hope is that it stays there, but as I age, I know it’s probable that I’ll find it in other spots eventually.

    Do take care, Connie. I hope I’ve answered your questions! Sending hugs,
    Wren 🙂

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