Rheumatoid factor

From Wikipedia the free encyclopedia

Rheumatoid factor (RF) is the autoantibody that was first found in rheumatoid arthritis. It is defined as an antibody against the Fc portion of IgG and different RFs can recognize different parts of the IgG-Fc.[1] RF and IgG join to form immune complexes that contribute to the disease process such as chronic inflammation and joint destruction at the synovium and cartilage.[2]

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,[3] IgE,[4] IgD.[5]


RF is tested by collecting blood in a plain tube (5 mL is often enough). The serum is tested for the presence of RF. There are different methods available, which include nephelometry, turbidimetry, agglutination of gamma globulin-coated latex particles or erythrocytes. 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.[6]

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.[7] The sensitivity of RF for established rheumatoid arthritis is only 60–70% with a specificity of 78%.[8]

Rheumatoid factor is part of the 2010 ACR/EULAR classification criteria for rheumatoid arthritis. RF positivity combines well with anti-CCP and/or 14-3-3η (YWHAH) to inform diagnosis. [9] RF positivity at baseline has also been described as a good prognostic marker for future radiographic damage. [10]


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%).[11] The higher the level of RF the greater the probability of destructive articular disease.[citation needed] 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.[12][13]

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


The test was first described by Norwegian Dr Erik Waaler in 1940 and redescribed by Dr Harry 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.[19][20]


  1. ^ Falkenburg, W.J.J. (November 2015). "IgG Subclass Specificity Discriminates Restricted IgM Rheumatoid Factor Responses From More Mature Anti–Citrullinated Protein Antibody–Associated or Isotype-Switched IgA Responses". Arthritis & Rheumatology. 67 (12): 3124–3134. doi:10.1002/art.39299. PMID 26246004.
  2. ^ Edkins A, Cushley W (2012). "The Jekyll and Hyde nature of antibodies". Biological Sciences Review. 25 (2): 4.
  3. ^ 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.
  4. ^ 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.
  5. ^ 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.
  6. ^ Rheumatoid Arthritis~workup at eMedicine
  7. ^ 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. S2CID 6941129.
  8. ^ 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. S2CID 6640507.
  9. ^ Zhang Y, Liang Y, Feng L, Cui L. Diagnostic performance of 14-3-3η and anti-carbamylated protein antibodies in Rheumatoid Arthritis in Han population of Northern China. Clin Chim Acta. 2020 Mar;502:102-110. doi: 10.1016/j.cca.2019.12.011. Epub 2019 Dec 17. PMID: 31862264.
  10. ^ Bukhari M, Lunt M, Harrison BJ, Scott DG, Symmons DP, Silman AJ. Rheumatoid factor is the major predictor of increasing severity of radiographic erosions in rheumatoid arthritis: results from the Norfolk Arthritis Register Study, a large inception cohort. Arthritis Rheum. 2002 Apr;46(4):906-12. doi: 10.1002/art.10167. PMID: 11953966.
  11. ^ Rheumatoid Factor - Patient UK
  12. ^ [1][full citation needed]
  13. ^ The Arthritis Association, Report by MHC 19.2
  14. ^ a b c d "Rheumatoid factor - Mayo Clinic". Mayo Clinic.
  15. ^ a b c d e f g Johnson, Jon (21 July 2021). "Rheumatoid factor: Ranges, tests, and treatment". Medical News Today. Retrieved 13 May 2022.
  16. ^ Ragab, Gaafar; Hussein, Mohamed A. (2017-03-01). "Vasculitic syndromes in hepatitis C virus: A review". Journal of Advanced Research. 8 (2): 99–111. doi:10.1016/j.jare.2016.11.002. ISSN 2090-1232. PMC 5272950. PMID 28149646.
  17. ^ Garcia-De La Torre, Ignacio (1993). "Autoimmune phenomena in leprosy, particularly antinuclear antibodies and rheumatoid factor". The Journal of Rheumatology. 20 (5): 900–3. PMID 8336322.
  18. ^ Atta, AM (2007). "Serum markers of rheumatoid arthritis in visceral leishmaniasis: rheumatoid factor and anti-cyclic citrullinated peptide antibody". Journal of Autoimmunity. 28 (1): 55–8. doi:10.1016/j.jaut.2006.12.001. PMID 17257811.
  19. ^ Waaler, Erik (2009). "On the Occurrence of a Factor in Human Serum Activating the Specific Agglutination of Sheep Blood Corpuscles". Acta Pathologica et 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. S2CID 221426678.
  20. ^ 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. S2CID 36340687.

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