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Seropositive Rheumatoid Arthritis: Your Guide

Posted on April 02, 2021
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Medically reviewed by
Ariel D. Teitel, M.D., M.B.A.
Article written by
Emily Wagner, M.S.

Not long ago, a rheumatoid arthritis (RA) diagnosis relied on the presence of an antibody known as rheumatoid factor (RF). The presence of RF classified a case as seropositive. It is now known that RF is present in other conditions, including infection and Sjögren’s syndrome. Today, seropositivity is defined by the appearance of other, more specific antibodies.

What Is Seropositive Rheumatoid Arthritis?

Seropositive RA is identified when certain proteins known as anti-cyclic citrullinated peptides (anti-CCPs) are present in the bloodstream. Anti-CCPs are also known as anti-citrullinated protein antibodies (ACPAs). A simple blood test can help your doctor determine if these antibodies are in your blood.

Up to 80 percent of people with RA will have anti-CCP antibodies. Studies have found that these antibodies can be detected in the blood five to 10 years before a person shows RA symptoms.

How Does It Differ From Seronegative Rheumatoid Arthritis?

The major difference between seropositive RA and seronegative RA is that in seronegative RA, no anti-CCP antibodies are detected in the blood. Seronegativity is less common and makes it more difficult to diagnose RA. In addition to the presence or absence of certain antibodies, there are a few other differences between seropositive and seronegative RA.

Shared Epitope

People with seropositive RA all share a common sequence of amino acids, known as a shared epitope. This sequence is encoded in the human leukocyte antigen (HLA) gene site that is responsible for controlling immune responses. Although the exact role of this sequence in RA is unknown, it is believed that it attaches to citrullinated proteins. This triggers the production of anti-CCP antibodies, which then leads to seropositivity.

Risk of Other Symptoms

People with seropositive RA are more likely to develop extra-articular manifestations (symptoms that develop outside of the joints) and other health conditions.

For example, rheumatoid nodules (firm lumps found under the skin near joints) occur in 20 percent to 30 percent of cases of RA, nearly all of which are seropositive cases.

People with seropositive RA may also be more likely to develop rheumatoid vasculitis. Vasculitis is caused by inflamed blood vessels that are damaged over time, leading to reduced blood flow in the involved area. Rheumatoid vasculitis typically develops in people who have had seropositive RA for 10 years or more. Symptoms of rheumatoid vasculitis include skin sores and pain in the fingers and toes, among other potentially serious complications.

People with seropositive RA are also more likely to develop cardiovascular disease. There is an increased risk of atherosclerosis, or the buildup of fat and cholesterol on artery walls. This buildup blocks blood flow through the artery, which can cause blood clots.

People with seropositive RA are also more likely to develop lung complications.

How Is Seropositive RA Diagnosed?

Rheumatoid arthritis is diagnosed through laboratory and imaging tests. These help your doctor or rheumatologist determine whether you have RA or another autoimmune disease.

Several laboratory tests can be performed to diagnose RA, mainly by determining the level of inflammation in the body. One test determines something called erythrocyte sedimentation rate (ESR), which is the rate at which red blood cells settle in a test tube over the course of one hour. C-reactive protein (CRP) levels can also be measured to determine levels of inflammation. These tests are not specific to RA but instead can show how severe disease activity is.

Other blood tests can help your doctor determine if you have seropositive or seronegative RA. These tests look for rheumatoid factor and anti-CCP antibodies. If these antibodies are found, you will likely be diagnosed with seropositive RA.

Imaging tests, such as ultrasound and X-rays, can look for joint inflammation and joint damage to help confirm a diagnosis and track disease progression.

How Does Seropositivity Affect Treatment?

Generally, the available treatments for RA can be used to treat both seropositive and seronegative cases. The types of medication you will receive depend on how long you have had RA and how severe your symptoms are. RA treatments work by targeting the source of inflammation or treating symptoms. Treatments may include:

Connect With Others Who Understand

On myRAteam, you’ll have access to the social network for people living with RA and their loved ones. Here, more than 146,000 members come together to ask questions, give advice, and share their stories with others who understand life with RA.

Are you living with seropositive RA? Share your experience in the comments below, or share your story on myRAteam.

Ariel D. Teitel, M.D., M.B.A. is the clinical associate professor of medicine at the NYU Langone Medical Center in New York. Review provided by VeriMed Healthcare Network. Learn more about him here.
Emily Wagner, M.S. holds a Master of Science in biomedical sciences with a focus in pharmacology. She is passionate about immunology, cancer biology, and molecular biology. Learn more about her here.

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