When You’re Seronegative for RA

If you’re seronegative for rheumatoid arthritis (RA), you may or may not have RA. It can make it harder to get an RA diagnosis.

Being seronegative for RA means that a blood test doesn’t find certain antibodies your body typically makes when you have the condition. So if you are seronegative for them, an RA diagnosis would have to be based on symptoms and other things.

The issue here is antibodies called rheumatoid factor (RF) and anti-cyclic citrullinated peptides (anti-CCPs).

Most people with RA -- between 60% and 80% -- make RF and anti-CCPs. But those antibodies are also found with other diseases. So by themselves, they aren’t enough to diagnose RA.

The levels of RF and anti-CCPs can be different for everyone. If your levels are very low, a blood test might not find them. This is called being “seronegative.” And as RA worsens, your levels may rise high enough to show up, and your diagnosis may change to “seropositive” for RA.

How Being Seronegative Affects Your Diagnosis

Being seronegative may make it harder to know for sure if you have RA. If you have symptoms of the disease but your blood tests don’t flag RF and anti-CCP antibodies, your doctor probably will give you a physical exam and recommend X-rays to look for signs of inflammation and joint damage.

Your doctor will check for the following symptoms of RA:

Keep in mind that other conditions can cause similar issues, and that can make seronegative RA even harder to diagnose. These include certain types of arthritis, like:

Research shows that people who smoke or are obese may be more likely to be seronegative.

How Being Seronegative Affects RA Symptoms

People who are seronegative are sometimes thought to have milder symptoms of RA, but that’s not always the case. The condition affects everyone differently, and symptoms can change over time.

But one possible difference is that people who are seropositive commonly get firm lumps on or near their affected joints called rheumatoid arthritis nodules. People who are seronegative generally don’t get these nodules.


Effects on RA Treatment

Doctors treat seronegative RA the same way they approach seropositive RA: Because there’s no cure, the goal is to ease your symptoms and keep the condition from getting worse.

To do this, doctors usually recommend:

  • Medications, including non-steroidal anti-inflammatories (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), and steroid shots
  • Physical therapy to help with moving around, range of motion, and pain
  • Exercise to build strength and lower stress
  • Surgery if you need joint replacement or reconstruction
  • Your doctor may consider whether fish oil and plant oils (such as primrose or borage oil) might help and whether they’re OK for you to try.

Most medications work the same for RA whether you’re seropositive or seronegative. But some research shows that a very small number of them may not work as well for people who don’t seem to have either RF or anti-CCP antibodies. Your doctor will advise you on what might work best for you.

How Being Seronegative Affects RA

As with people who are seropositive, RA isn’t predictable for those who are seronegative. But because it can be harder to diagnose seronegative RA, it can take longer to get treated for it. That delay might make it less likely that you’ll go into remission, which is when you have very few signs of the disease.

People who start treatment within the first 2 years of symptoms are more likely to go into remission than those who don’t.

WebMD Medical Reference Reviewed by Brunilda Nazario, MD on September 26, 2020



CDC: “Rheumatoid Arthritis (RA).”

Arthritis Foundation: “What ‘Type’ of RA Do You Have?” “Your RA Is In Remission! Now What?”

University of Central Florida Health: “Seronegative Rheumatoid Arthritis.”

Rheumatoid Arthritis Support Network: “Seronegative RA: What Are the Symptoms of Seronegative RA?” “Rheumatoid Nodules: Are Rheumatoid Nodules Dangerous?”

Mayo Clinic: “Gout,” “Evidence of Diagnostic and Treatment Delay in Seronegative Rheumatoid Arthritis: Missing the Window of Opportunity.”

National Rheumatoid Arthritis Society: “Seropositive & Seronegative.”

National Psoriasis Foundation: “About Psoriatic Arthritis.”

American College of Rheumatology: “Spondyloarthritis.”

National Center For Biotechnology Information: “Disease Modifying Anti-Rheumatic Drugs (DMARD).”

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