What Is Seropositive Rheumatoid Arthritis?

Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the joints. The most common type of RA is seropositive RA, where someone with RA has detectable anti-cyclic citrullinated peptide (anti-CCP) and/or rheumatoid factor (RF) antibodies in their blood that can identify the disease.

High levels of one or both are associated with inflammation and increased disease severity. By definition, people with seronegative RA do not have detectable anti-CCP or RF levels.

Having seropositive RA doesn’t mean you should lose all hope. Many of the current treatment options can allow for people with RA—regardless of the type of RA they have—to slow down disease progression and enjoy a good quality of life. 

RF and Anti-CCP Proteins

A significant number of people with RA are seropositive. The development of RA, its severity, and whether it is seropositive are dependent on rheumatoid factor and anti-CCP proteins. The percentage of people with RA who will test positive for rheumatoid factor is 70–90%.

RF is a protein antibody the immune system produces that is associated with inflammation in the joints. High levels of RF tend to be associated with conditions like RA, but it also occurs in other chronic medical conditions. It is also possible for RF to be detectable in healthy people and for people with RA to have normal/negative RF levels.

In contrast, anti-CCP is more specific to RA and can show up many years before you even develop symptoms. Much like RF proteins, anti-CPP antibodies are associated with inflammation in the joints and may even contribute to direct attack on joint tissues. A comparative study reported in 2014 found anti-CCP antibodies in 69% of individuals with RA.

Specific causes of RA are unknown although researchers speculate that RA is related to a combination of genetic and environmental factors. The heritability of seropositive RA is around 40 to 65%.

Seropositive RA Symptoms

RA has a specific set of symptoms associated with it, and these will come and go throughout your life. You will have periods where disease activity and symptoms are high­—called flare-ups—and periods of remission where you experience only a few or no symptoms.

Specific symptoms of RA may include:

  • Pain and swelling of joints, especially of the hands and feet
  • Several affected joints
  • Symmetrical joint pain—meaning the same joints on both sides of the body are affected
  • Stiffness in the morning that lasts 30 or more minutes
  • Deterioration of cartilage and bone shown on X-rays
  • Development of rheumatoid nodules—firm lumps under the skin near joints

Other symptoms of RA that are also seen in other autoimmune diseases and similar conditions include:

  • Chronic fatigue
  • Depression
  • Anemia
  • Muscle pain

The research shows people with seropositive RA tend to have more severe symptoms than those who are seronegative—although this doesn’t apply to everyone. Treatment outcomes may not as positive as they would be for seronegative RA.

People with seropositive RA are more likely to develop complications of the disease, including rheumatoid vasculitis (inflammation of blood vessels), and rheumatoid lung disease. They also have a higher risk for comorbid conditions of RA, like cardiovascular disease and depression.

Rheumatoid Arthritis Healthcare Provider Discussion Guide

Get our printable guide for your next healthcare provider's appointment to help you ask the right questions.

Doctor Discussion Guide Old Woman

Seropositive vs. Seronegative

The number of people affected by RA in the United States is around 1.3 million people, according to the American College of Rheumatology. That number hasn’t really changed, but what has changed is the reduced number of people with seropositive RA.

A 2019 analysis out of the Mayo Clinic published in the journal Annals of the Rheumatic Diseases reports that from 1985 to 1994, only 12 out of every 100,000 people with RA were seronegative (RF negative). And from 2005 to 2014, that number went up to 20 out of every 100,000 people.

People with seronegative RA will test negative for RF and anti-CCP proteins. They are diagnosed based on other criteria for RA like swollen joints and radiological joint changes.

A study published in 2016 by the journal Rheumatology finds that 38% percent of people diagnosed with RA are seronegative. Sometimes, people with seronegative RA will go on to be seropositive especially those with extremely low levels of RF or anti-CCP.

Here, researchers found seronegative RA could affect the wrists, ankles, and large joints while seropositive RA didn't cause the same destruction of these joints. Seropositive RA can still cause joint damage and disability, but seronegative RA seems to affect specific joints more often.

Many experts believe people with seropositive RA have more severe disease symptoms. However, some cases of seronegative rheumatoid arthritis can be severe, as illustrated by a 2015 BMC Musculoskeletal Disorders report.

The researchers concluded that further study was needed to better understand the long-term outcomes of both seronegative and seropositive RA. Furthermore, a 2018 comparative study reported by PLoS One indicates that compared to people with seropositive RA, those with seronegative RA start off with more severe symptoms but respond better to therapy. Additionally, both seronegative and seropositive types may have similar radiographic damage.

The researchers also noted that people with seronegative RA have better responses to treatment than do people with seropositive RA, which might give some insight as to why they may have more severe disease.


No matter what type of RA you have, your treatment options will be the same. Treatment will focus on managing pain and inflammation and preventing damage to joints. For both types, RA treatment may include a combination of medications, lifestyle changes, complementary therapies, and surgery.


Your healthcare provider may prescribe one or more of the following medications to help manage your symptoms:

Clinical Guidelines for Treating RA

Clinical guidelines published in 2021 by the American College of Rheumatology recommend that methotrexate should be the first DMARD tried for most people with moderate to severe RA. This applies to both seropositive and seronegative RA.

Lifestyle Changes

Lifestyle habits like diet and exercise may help you manage seropositive RA. Eating an anti-inflammatory diet may help you to reduce the number of RA flare-ups you have. A healthy diet can also reduce your risk for other diseases, especially those considered comorbidities of RA.

Exercise can help you to keep your joints mobile and build strength in your muscles. Ask your healthcare provider about how you can safely incorporate exercise into your RA treatment plan.

It is also a good idea to not smoke with RA. Smoking is linked to more severe disease in RA and it can reduce the effectiveness of some of the treatments you take to manage RA. It is especially important for people with seropositive RA because they don’t respond as well to treatment—regardless of whether they smoke or not.

Complementary Therapies

Your healthcare provider may suggest physical and occupational therapy to teach you exercises to help you keep your joints mobile and flexible. Your therapist may also suggest ways of doing daily tasks that don’t put as much pressure on your joints.

An occupational therapist can suggest assistive devices so that you are not stressing painful joints. This includes things like a cane, button hooks to help you with getting dressed, or a reacher to help you grab objects without having to reach.


When medications fail to prevent or slow down damage to bones and joints, your healthcare provider may suggest surgery. Surgery may help restore the ability to use a joint, reduce pain, and improve function.

A Word From Verywell

There is no cure for seropositive rheumatoid arthritis, but effective management of the disease means you can still enjoy a good quality of life. You should contact your healthcare provider as soon as you start to experience symptoms of RA. Early diagnosis and treatment could potentially mean less joint disease and reduced disease progression.

9 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Ingegnoli F, Castelli R, Gualtierotti R. Rheumatoid factors: Clinical applications. Dis Markers. 2013;35(6):727-734. doi:10.1155/2013/726598

  2. Eker YÖ, Pamuk ÖN, Pamuk GE et al. The frequency of anti-CCP antibodies in patients with rheumatoid arthritis and psoriatic arthritis and their relationship with clinical features and parameters of angiogenesis: A comparative study. Eur J Rheumatol. 1(2):67-71. doi:10.5152/eurjrheumatol.2014.022

  3. Choi S, Lee KH. Clinical management of seronegative and seropositive rheumatoid arthritis: A comparative study. PLoS One. 13(4):e0195550. doi:10.1371/journal.pone.0195550

  4. Harvard University. Rheumatoid arthritis: what is it?

  5. Duarte-Garcia A. American College of Rheumatology. Rheumatoid arthritis.

  6. Myasoedova E, Davis J, Matteson EL, Crowson CS. Is the epidemiology of rheumatoid arthritis changing? Results from a population-based incidence study, 1985-2014. Ann Rheum Dis. 79(4):440-444. doi:10.1136/annrheumdis-2019-216694 

  7. De Winter LM, Hansen WL, van Steenbergen HW, et al. Autoantibodies to two novel peptides in seronegative and early rheumatoid arthritis. Rheumatology (Oxford). 55(8):1431-6. doi:10.1093/rheumatology/kew198 

  8. Nikiphorou E, Sjöwall C, Hannonen P, et al. Long-term outcomes of destructive seronegative (rheumatoid) arthritis - description of four clinical cases. BMC Musculoskelet Disord. 17:246. doi:10.1186/s12891-016-1067-y

  9. Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 73(7):924-939. doi:10.1002/acr.24596

By Lana Barhum
Lana Barhum has been a freelance medical writer since 2009. She shares advice on living well with chronic disease.