Quick Notes

  • Rheumatoid Factor (RF) may help rule in Rheumatoid Arthritis (RA)
  • RF testing isn't perfect: some with Rheumatoid Arthritis will show low RF titres, some healthy people will show moderate RF titres, and some normal people will even show high RF Titres
  • Anti-CPP is a newer test, which is very helpful in diagnosing Rheumatoid Arthritis
  • Doing RF and Anti-CPP together is best for investigating Rheumatoid Arthritis.


Testing for Rheumatoid Arthritis (or any autoimmune disease) can be a difficult, confusing process. We have certain tests that measure autoantibodies. Autoantibodies are the part of our immune system, which could attach our own tissue and cause debilitating autoimmune disease, such as Rheumatoid Arthritis.

The presence of autoantibodies in a patient DOES NOTassure the diagnosis of an autoimmune disease. In fact, most healthy individuals have some autoantibodies [1]. Additionally, the testing methods themselves are not perfect.

Rheumatoid Factor (RF)

IgM and IgG are antibodies found throughout our bodies. Abnormal IgG antibodies found in the joint fluid act as antigens (the things other parts of the immune system may attack). Rheumatoid factor is an IgM autoantibody which attacks the Fc portion of IgG antibody. The simple video below depicts how RF and IgG interact.

When RF attacks IgG, an immune complex is formed. These immune complexes activate something called the complement system (another piece of our immune system) as well as other inflammatory systems. All these things together cause the damage - through inflammation. Not only is this happening at the joints, but perhaps at the blood vessels, lungs, nerves and heart [3].

Rheumatoid Factor and Rheumatoid Arthritis

RF helps us make a diagnosis of Rheumatoid Arthritis. RF one of the things being measured if you've ever heard of the term seropositive Rheumatoid Arthritis.

It's not perfect.

It's thought to be present in about 70-80% of those with Rheumatoid Arthritis, which means if you're found to be RF negative, there is still a chance you have Rheumatoid Arthritis. Further testing can still be warranted [1] [3]. RF is absent in 15-20% of people who have Rheumatoid Arthritis.

About 15% of the healthy population have a low titer of RF and 5% of the population has a higher titre.

As we age, we naturally make more RF, in fact, 20% of people over 65 years of age have elevated RF[2], but wouldn't qualify as having Rheumatoid Arthritis.

Quantifying RF

As mentioned above, RF is not a perfect marker. It's not particularly accurate in testing RF, some people who have Rheumatoid Arthritis don't have elevated RF and some people who have RF don't have the disease.

Finding out as much about Rheumatoid Factor is important. RF positive patients are more likely to have progressive, erosive arthritis with loss of joint mobility [1] and extra-articular (outside the joint) involvement such as lung and blood vessels [1].

Confirming a Diagnosis

To confirm RF detection, we use anti-cyclic citrullinated peptide antibodies (anti-CPP) [2].

Cyclic Citrullinated Peptide (CPP)

CPP is  formed when there is inflammation in the body. With inflammation, citrulline gets driven into certain proteins. In Rheumatoid Arthritis, autoantibodies are formed against this citrulline-contianing protein. The antibody is called an anti-CPP antibody [1].

Anti CPP and Rheumatoid Arthritis

CPP is a somewhat more recently discovered biomarker of Rheumatoid Arthritis[1]. Those with positive anti-CPP tend to have more severe, erosive and aggressive disease.

Timing is Important

Anti-CPP is produced early in the course of Rheumatoid Arthritis[4]. Patients who have Rheumatoid Arthritis may not see elevations in Rheumatoid Factor (RF) in the early stages. In the early goings, anti-CPP may be high. It's especially important to catch early cases of Rheumatoid Arthritis joint destruction may already be underway. Anti-CPP antibodies typically rises years before the clinical onset of arthritis [4].

Anti-CPP is Very Accurate

The presence of anti-CPP antibodies are about 99.3% specific for the diagnosis of Rheumatoid arthritis. Sensitivity of this test is about 67.5%. Click here for more details about testing sensitivity and specificity. Usually, testing for Rheumatoid Factor (RF) and Anti-CPP are done together.

Who is this Test Useful for?

  • Anyone with suspected rheumatoid arthritis
  • Patients with unexplained joint inflammation, especially when RF is negative or below 50 units/ml [4].

Testing for Rheumatoid Arthritis? Test RF and Anti-CPP Together

When done together, the sensitivity for a Rheumatoid Arthritis diagnosis is around 99.1% [4].


Due to the complicated nature of autoimmune testing, patients and doctors need to be aware of the various tests available and navigate the testing work to come up with a diagnosis. Making a diagnosis is important as we can tailor treatment and focus on slowing disease progression.


About the Author - Dr. Johann de Chickera

man facing camera

Dr. Johann is a fully licensed Naturopathic Doctor. His approach emphasizes the importance of living a healthy lifestyle and improving one’s health naturally. Dr. Johann obtained a Doctor of Naturopathy at the Canadian College of Naturopathic Medicine (CCNM). Education at CCNM is a vigorous four years, with a curriculum involving biomedical sciences, physical diagnosis, clinical nutrition, traditional Chinese medicine and acupuncture, botanical (herbal) medicine, physical medicine, homeopathy and lifestyle management.

While Dr. Johann has a general practice, he focuses on fertility, hormonal imbalances, gut health, and autoimmune disease.

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