What does seronegative rheumatoid arthritis mean?
Seronegative rheumatoid arthritis (RA) is a topic that brings a lot of confusion for the public, people living with rheumatoid disease, and sometimes even medical professionals. Put simply, seronegative is a term used to when there is an absence of an antibody that is usually found with a certain disease.1 The word has two parts: “sero” is just short for serum—or blood—where biological markers—or biomarkers—are usually measured. Of course, “negative” just means that none was found—that the test couldn’t detect a sufficient amount of a marker.
Is seronegative rheumatoid arthritis a separate type of RA / RD?
Some of the questions that people ask:
- My doctors said my disease will be milder because I have seronegative RA.
- Can extra-articular disease happen with seronegative RA?
- Isn’t seronegative rheumatoid arthritis harder to treat?
These are all good questions. But can you see an underlying assumption in these questions? It sounds like seronegative rheumatoid arthritis is a different type of RA / RD. Sometimes seronegative disease is discussed like it’s an entirely different rheumatoid disease with different symptoms, treatments and outcomes.
In reality, it’s more like this:
All rheumatoid arthritis / rheumatoid disease is diagnosed using criteria—in the US set by the American College of Rheumatology (ACR). The criteria are a list of items that count as points toward diagnosis. The criteria were updated in 2010, but as we have discussed here on the blog before, they tend to recognize later stage rheumatoid disease. Blood tests for biomarkers anti-CCP and Rheumatoid factor are both included in the criteria.
Someone can be diagnosed with RA / RD by having “enough” points. A person who doesn’t have positive blood tests just has to get more points in another area—like swollen joints.
Why are tests “negative” in seronegative rheumatoid arthritis?
This is the important thing to remember—something I’ve probably typed a thousand times in comments or email replies over the years. “Seronegative” only means negative for the one biomarker that was tested. Many biomarkers have been found. Some of them we have tests for. But there are many more still to be identified. Someday it’s possible that no one would be told they have seronegative rheumatoid arthritis.
Rheumatoid factor (RF) tends to be negative early on in the disease process. It tends to be higher later in the disease process. Saying “seronegative” used to mean negative RF, period. Nowadays, many doctors say someone is seropositive if they have antibodies to CCP (also called ACPA). And they should, since those are the most specific antibodies we have for RA / RD.
Fascinating poster on seronegative rheumatoid arthritis
You might also like to read:
- 14-3-3eta Marker in Rheumatoid Arthritis Patients with Low CRP
- Mascara, Antibodies, and Soup: All I Know about a Disease
Let’s consider this poster from the ACR meeting with a simple but fascinating conclusion about seronegative rheumatoid arthritis: Comparison of Clinical Features of Seronegative and Seropositive Early Rheumatoid Arthritis.2
They found that newly diagnosed RA patients in their study had higher disease activity compared to the seropositive patients, as measured by tender and swollen joints. They concluded that this is an effect of the classification criteria discussed above because “more involved joints are required for seronegative patients to fulfil the criteria.”
People with seronegative disease have to get more points elsewhere since they don’t get points for blood markers. This study casts doubt on the historical belief that seronegative disease is a milder form of the disease. It is most likely, as I said, the very same disease, but with markers that we cannot test for yet.
Have you or someone you know been diagnosed with seronegative rheumatoid arthritis? What questions did you have about this? Could you find answers?
Today is the perfect day to talk about what rheumatoid disease really is! Tomorrow is the 7th annual Rheumatoid Awareness Day. To see all the action or get involved, visit rheum4us.org. Hint: cool video shorts & a HUGE matching grant to make our small donations count BIG!
- 4 Benefits of a New ACPA Rheumatoid Arthritis Test
- New Biomarkers for Rheumatoid Arthritis /Rheumatoid Disease
- Blood Tests for Rheumatoid Arthritis: What Is Their Role?
MORE ON BIOMARKERS: Coming up soon on the RPF blog at rheum4us.org, my immunologist daughter KB is publishing a short and easy 101 on biomarkers. That will be a big help to everyone learning about seronegative RA. You should really subscribe there NOW anyway to get all the news on Rheumatoid Awareness Day!
1 seronegative. (n.d.) Farlex Partner Medical Dictionary. (2012). Retrieved January 27 2019 from https://medical-dictionary.thefreedictionary.com/seronegative
2 Giacovelli G, Barbetta B, Vitalini C, Brambilla N, D’Amato M, Girolami F, Rovati LC. Comparison of Clinical Features of Seronegative and Seropositive Early Rheumatoid Arthritis: Blinded Data from the Ongoing Phase IIb Trial with the EP4 Receptor Antagonist CR6086 in DMARD-Naïve Patients [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/comparison-of-clinical-features-of-seronegative-and-seropositive-early-rheumatoid-arthritis-blinded-data-from-the-ongoing-phase-iib-trial-with-the-ep4-receptor-antagonist-cr6086-in-dmard-naive-patien/. Accessed January 26, 2019.