Rheumatoid factors are autoantibodies (IgM usually) which bind to the Fc region of IgG. Autoantibodies are proteins that are produced by the immune system, but rather than attacking foreign substances, they attack the body's own tissues. The earliest assays (i.e., tests) that suggested autoantibodies were associated with rheumatoid arthritis were developed in the 1940s. Early on, these were agglutination tests -- serum from rheumatoid arthritis patients was shown to cause agglutination of sheep red blood cells that had been sensitized with rabbit anti-sheep erythrocyte antibodies. There were several modifications made to the original agglutination test, primarily substituting IgG-coated latex beads for the sheep cells. Later, the ELISA (enzyme-linked immunosorbent assay) test for rheumatoid factor was developed, as well as nephelometry tests.
In agglutination tests, clumping is indicative of a positive result. Serial dilutions can then be made with the test sample to determine the titer. The titer indicates how much the sample can be diluted before the rheumatoid factor is undetectable (does not clump).
In nephelometry tests, a blood sample is mixed with antibodies to cause clumping. A light is passed through the sample to determine the degree of cloudiness.
Understanding the Results
Typically, the normal range for the rheumatoid factor test is reported as:
- Less than 40-60 u/mL
- Less than 1:80 (titer)
Note: Different laboratories can vary in test method or test kit used, so follow the results and normal range offered by your specific laboratory.
Results of rheumatoid factor tests can be confusing for arthritis patients. First and foremost, the most important thing to know is that the rheumatoid factor test is just one piece of information used to formulate a diagnosis. A definitive diagnosis is never based solely on the result of the rheumatoid factor test. Here are other essential facts about the rheumatoid factor test that you should know:
- Rheumatoid factor can be positive in healthy people (in 1% of younger people and up to 5% of those over 70 years old).
- Rheumatoid factor can be positive in non-rheumatoid arthritis diseases and conditions (e.g., infections, cancer) or in rheumatic conditions other than rheumatoid arthritis (e.g., Sjogren's syndrome or lupus).
- Rheumatoid factor can be detected in the blood up to 10 years before rheumatoid arthritis symptoms appear. However, in a sub-group of rheumatoid arthritis patients, rheumatoid factor is detectable after symptoms appear.
- Rheumatoid arthritis patients who are positive for rheumatoid factor (seropositive) tend to have more aggressive disease, while patients who are negative for rheumatoid factor (seronegative) have less severe disease and fewer bone erosions.
- About 20% of people diagnosed with rheumatoid arthritis remain negative for rheumatoid factor throughout the course of their disease.
Clinical Relevance of the Results
A rheumatoid factor test result that is initially negative can later turn positive, but the clinical relevance of that fact remains in question. According to Scott Zashin, M.D., rheumatologist from Dallas, Texas (scottzashinmd.com) and author of Arthritis Without Pain - The Miracle of TNF Blockers and co-author of my second book Natural Arthritis Treatment, "Rheumatologists typically do not follow rheumatoid factor once a diagnosis of rheumatoid arthritis is made. That being said, in my experience, the level of the rheumatoid factor may change somewhat with disease activity, but that is not as clinically useful as other tests, such as the erythrocyte sedimentation rate, C-reactive protein (CRP), and in some cases other markers that may be found in the VECTRA tests, that are used to assess disease activity in rheumatoid arthritis."
Kelley's Textbook of Rheumatology. Ninth Edition. Autoantibodies in Rheumatoid Arthritis. Chapter 56. Felipe Andrade et al. p. 804.
Primer on the Rheumatic Diseases. Thirteenth Edition. Published by the Arthritis Foundation. Chapter 6. Rheumatoid Arthritis. Rheumatoid Factors. p. 126.
Rheumatoid Factor (RF). MedlinePlus. Updated 4/20/2013.