Rheumatoid factor

Not to be confused with Rhesus factor.

Rheumatoid factor (RF) is the autoantibody (antibody directed against an organism's own tissues) that was first found in rheumatoid arthritis. It is defined as an antibody against the Fc portion of IgG (an antibody against an antibody). RF and IgG join to form immune complexes that contribute to the disease process.[1]

Rheumatoid factor can also be a cryoglobulin (antibody that precipitates on cooling of a blood sample); it can be either type 2 (monoclonal IgM to polyclonal IgG) or type 3 (polyclonal IgM to polyclonal IgG) cryoglobulin.

Although predominantly encountered as IgM, rheumatoid factor can be of any isotype of immunoglobulins, i.e. IgA, IgG, IgM,[2] IgE,[3] IgD.[4]


RF is often evaluated in patients suspected of having any form of arthritis even though positive results can be due to other causes, and negative results do not rule out disease. But, in combination with signs and symptoms, it can play a role in both diagnosis and disease prognosis. It is part of the usual disease criteria of rheumatoid arthritis.[5]

The presence of rheumatoid factor in serum can also indicate the occurrence of suspected autoimmune activity unrelated to rheumatoid arthritis, such as that associated with tissue or organ rejection. In such instances, RF may serve as one of several serological markers for autoimmunity.[6] The sensitivity of RF for established rheumatoid arthritis is only 60-70% with a specificity of 78%.[7]

Many patients with rheumatoid disease are seronegative to begin with but seroconvertion (becoming positive) occurs in 80% of them.[8]


High levels of rheumatoid factor (in general, above 20 IU/mL, 1:40, or over the 95th percentile; there is some variation among labs) occur in rheumatoid arthritis (present in 80%) and Sjögren's syndrome (present in 70%).[9] The higher the level of RF the greater the probability of destructive articular disease. It is also found in Epstein-Barr virus or Parvovirus infection and in 5-10% of healthy persons, especially the elderly.

There is an association between rheumatoid factor and more persistently active synovitis, more joint damage, greater eventual disability and Arthritis.[10][11]

Other than in rheumatoid arthritis, rheumatoid factor may also be elevated in:


The test was first described by Norwegian Dr Erik Waaler in 1940 and redescribed by Dr H.M. Rose and colleagues in 1948. Redescription is said to be due to the uncertainties due to World War II. It is still referred to as the Waaler-Rose test.[12][13]


  1. Edkins A, Cushley W (2012). "The Jekyll and Hyde nature of antibodies". Biological Sciences Review. 25 (2): 4.
  2. Hermann, E; Vogt, P; Müller, W (1986). "Rheumatoid factors of immunoglobulin classes IgA, IgG and IgM: Methods of determination and clinical value". Schweizerische medizinische Wochenschrift. 116 (38): 1290–7. PMID 3775335.
  3. Herrmann, D; Jäger, L; Hein, G; Henzgen, M; Schlenvoigt, G (1991). "IgE rheumatoid factor. Occurrence and diagnostic importance in comparison with IgM rheumatoid factor and circulating immune complexes". Journal of investigational allergology & clinical immunology. 1 (5): 302–7. PMID 1669588.
  4. Banchuin, N; Janyapoon, K; Sarntivijai, S; Parivisutt, L (1992). "Re-evaluation of ELISA and latex agglutination test for rheumatoid factor detection in the diagnosis of rheumatoid arthritis". Asian Pacific Journal of Allergy and Immunology. 10 (1): 47–54. PMID 1418183.
  5. Rheumatoid Arthritis~workup at eMedicine
  6. Rostaing, Lionel; Modesto, Anne; Cisterne, Jean Marc; Izopet, Jacques; Oksman, Françoise; Duffaut, Michel; Abbal, Michel; Durand, Dominique (1998). "Serological Markers of Autoimmunity in Renal Transplant Patients with Chronic Hepatitis C". American Journal of Nephrology. 18 (1): 50–6. doi:10.1159/000013304. PMID 9481439.
  7. Nishimura, K; Sugiyama, D; Kogata, Y; Tsuji, G; Nakazawa, T; Kawano, S; Saigo, K; Morinobu, A; Koshiba, M; Kuntz, KM; Kamae, I; Kumagai, S (5 June 2007). "Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis.". Annals of Internal Medicine. 146 (11): 797–808. doi:10.7326/0003-4819-146-11-200706050-00008. PMID 17548411.
  8. Pincus, T (2006). "Advantages and limitations of quantitative measures to assess rheumatoid arthritis: joint counts, radiographs, laboratory tests, and patient questionnaires.". Bulletin of the NYU hospital for joint diseases. 64 (1-2): 32–9. PMID 17121487.
  9. Rheumatoid Factor - Patient UK
  10. http://www.medicinenet.com/rheumatoid_factor/article.htm[]
  11. The Arthritis Association, Report by MHC 19.2
  12. Waaler, Erik (2009). "On the Occurrence of a Factor in Human Serum Activating the Specific Agglutination of Sheep Blood Corpuscles". Acta Pathologica Microbiologica Scandinavica. 17 (2): 172–188. doi:10.1111/j.1699-0463.1940.tb01475.x. reproduced in Waaler, E (2007). "On the Occurrence of a Factor in Human Serum Activating the Specific Agglutintion of Sheep Blood Corpuscles". APMIS. 115 (5): 422–38; discussion 439. doi:10.1111/j.1600-0463.2007.apm_682a.x. PMID 17504400.
  13. Rose, HM; Ragan, C (1948). "Differential agglutination of normal and sensitized sheep erythrocytes by sera of patients with rheumatoid arthritis". Proceedings of the Society for Experimental Biology and Medicine. 68 (1): 1–6. doi:10.3181/00379727-68-16375. PMID 18863659.

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