Understanding Seronegative RA | Arthritis Foundation

Microbiome, microbes, microorganisms – these terms may be confusing, but the types of bacteria living in and on our bodies can impact arthritis. Learn what helps or harms the microbiome and the health of your gut and discover dietary changes that can make a difference.
This episode was originally released on January 19, 2021.
Movement is the best medicine, even when your joints hurt. Your Exercise Solution (YES) is a resource to help you create a physical activity routine with modifications developed and approved by physical therapists.
Join the movement and make an impact by honoring those who rock your world at the Arthritis Foundation’s signature walk event, Walk to Cure Arthritis. Register as an individual or form a team and Rock the Walk in your community!
Many people originally diagnosed with seronegative rheumatoid arthritis turn out to have a different type of joint disease.
By Linda Rath | June 27, 2022
Some researchers believe rheumatoid arthritis (RA) isn’t a single disease but rather a collection of diseases. It might also be one disease with many different causes. However RA is eventually defined, there are two main subtypes in adults: seropositive and seronegative. In seropositive RA, blood tests show unusually high levels of antibodies called anti-cyclic citrullinated peptides (anti-CCPs). These are specific markers for RA and may show up as much as a decade before symptoms do. Around 60% to 80% of people diagnosed with RA have anti-CCPs. By definition, people with seronegative RA don’t have these antibodies in their blood, though that’s in some dispute.
Doctors once used an antibody called rheumatoid factor (RF) to test for seropositivity. Most people with anti-CCPs also have RF, but so do people with lots of other conditions, including infections. That’s why anti-CCP is now the preferred test, though an RF test is often used in conjunction with it for greater accuracy.
The Role of Blood Tests in RA Diagnosis
No single blood test can reliably diagnose RA. Some healthy people test positive for anti-CCPs, while others who have RA have negative test results. Blood tests are just one of several factors, including a medical history, physical exam and X-rays, that help doctors diagnose the disease. Still, antibodies are a pretty good indicator of RA if you have also have joint pain and swelling and damage to bones and cartilage on imaging tests.
Seronegative RA is more challenging and takes longer to diagnose because doctors try to rule out other types of arthritis that aren’t associated with high levels of anti-CCP, such as psoriatic arthritis, gout and spondyloarthritis.
Still, seronegative RA remains an imprecise diagnosis, according to some experts. It’s rare for someone who is seronegative to become seropositive, but it’s not uncommon for a diagnosis of seronegative RA to be changed to something else later on. In one study of nearly 10,000 people diagnosed with seronegative RA, more than 500 were subsequently found to have spondyloarthritis, 275 had psoriatic arthritis and 245 had axial spondyloarthritis. Since these forms of arthritis mainly affect the low back and spine and RA affects the hands and feet, it seems the original diagnosis was based solely on the absence of anti-CCP.
Another wrinkle: Some studies have found that about one-third of people diagnosed with seronegative RA actually have high levels of the same autoantibodies found in seropositive RA patients.
Seropositive vs. Seronegative: Which is worse?
In the debate about whether seropositive or seronegative patients have more severe disease, study results are mixed. A Dutch study found that people with seronegative disease had significantly more inflammation and disease activity than those with seropositive RA. And an international group of researchers reported a rare but particularly severe and destructive subtype of seronegative disease. Another study, however, reported similar disease activity and progression in both types of RA after two years.
A growing amount of research is devoted to seropositive and seronegative RA, but more is needed. For now, if you’re diagnosed with seronegative RA, ask why your doctor arrived at that diagnosis and consider getting a second opinion. If you have severe symptoms, talk to your doctor about using the same treat-to-target approach and medications prescribed for seropositive RA.
Tips to Tackle RA
Stay in the Know. Live in the Yes.
Get involved with the arthritis community. Tell us a little about yourself and, based on your interests, you’ll receive emails packed with the latest information and resources to live your best life and connect with others.
Donate
Every gift to the Arthritis Foundation will help people with arthritis across the U.S. live their best life.
Volunteer
Join us and become a Champion of Yes. There are many volunteer opportunities available.
Live Yes! INSIGHTS
Take part to be among those changing lives today and changing the future of arthritis.
Partner
Proud Partners of the Arthritis Foundation make an annual commitment to directly support the Foundation’s mission.
Donate
Ways to Give
Every gift to the Arthritis Foundation will help people with arthritis across the U.S. live their best life. Whether it is supporting cutting-edge research, 24/7 access to one-on-one support, resources and tools for daily living, and more, your gift will be life-changing.
Help millions of people live with less pain and fund groundbreaking research to discover a cure for this devastating disease. Please, make your urgently-needed donation to the Arthritis Foundation now!
Other Ways to Give
Volunteer
Volunteer Opportunities
The Arthritis Foundation is focused on finding a cure and championing the fight against arthritis with life-changing information, advocacy, science and community. We can only achieve these goals with your help. Strong, outspoken and engaged volunteers will help us conquer arthritis. By getting involved, you become a leader in our organization and help make a difference in the lives of millions. Join us and become a Champion of Yes.
Live Yes! INSIGHTS
Give Just 10 Minutes.
Tell us what matters most to you. Change the future of arthritis.
By taking part in the Live Yes! INSIGHTS assessment, you’ll be among those changing lives today and changing the future of arthritis, for yourself and for 54 million others. And all it takes is just 10 minutes.
Your shared experiences will help:
- Lead to more effective treatments and outcomes
- Develop programs to meet the needs of you and your community
- Shape a powerful agenda that fights for you
Now is the time to make your voice count, for yourself and the entire arthritis community.
Currently this program is for the adult arthritis community. Since the needs of the juvenile arthritis (JA) community are unique, we are currently working with experts to develop a customized experience for JA families.
How are you changing the future?
By sharing your experience, you’re showing decision-makers the realities of living with arthritis, paving the way for change. You’re helping break down barriers to care, inform research and create resources that make a difference in people’s lives, including your own.
Partner
Meet Our Partners
As a partner, you will help the Arthritis Foundation provide life-changing resources, science, advocacy and community connections for people with arthritis, the nations leading cause of disability. Join us today and help lead the way as a Champion of Yes.