Rheumatoid factor

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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]

Contents

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]

Testing

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. 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 to 70 percente with a specificity of 78 percent. [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]

Interpretation

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:

History

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]

Related Research Articles

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Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involved, with the same joints typically involved on both sides of the body. The disease may also affect other parts of the body, including skin, eyes, lungs, heart, nerves, and blood. This may result in a low red blood cell count, inflammation around the lungs, and inflammation around the heart. Fever and low energy may also be present. Often, symptoms come on gradually over weeks to months.

<span class="mw-page-title-main">Autoimmunity</span> Immune response against an organisms own healthy cells

In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". Prominent examples include celiac disease, diabetes mellitus type 1, Henoch–Schönlein purpura (HSP), systemic lupus erythematosus (SLE), Sjögren syndrome, eosinophilic granulomatosis with polyangiitis, Hashimoto's thyroiditis, Graves' disease, idiopathic thrombocytopenic purpura, Addison's disease, rheumatoid arthritis (RA), ankylosing spondylitis, polymyositis (PM), dermatomyositis (DM), and multiple sclerosis (MS). Autoimmune diseases are very often treated with steroids.

<span class="mw-page-title-main">Antinuclear antibody</span> Autoantibody that binds to contents of the cell nucleus

Antinuclear antibodies are autoantibodies that bind to contents of the cell nucleus. In normal individuals, the immune system produces antibodies to foreign proteins (antigens) but not to human proteins (autoantigens). In some cases, antibodies to human antigens are produced.

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<span class="mw-page-title-main">Immunoglobulin G</span> Antibody isotype

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<span class="mw-page-title-main">Cryoglobulinemia</span> Medical condition

Cryoglobulinemia is a medical condition in which the blood contains large amounts of pathological cold sensitive antibodies called cryoglobulins – proteins that become insoluble at reduced temperatures. This should be contrasted with cold agglutinins, which cause agglutination of red blood cells.

Autoimmune hemolytic anemia (AIHA) occurs when antibodies directed against the person's own red blood cells (RBCs) cause them to burst (lyse), leading to an insufficient number of oxygen-carrying red blood cells in the circulation. The lifetime of the RBCs is reduced from the normal 100–120 days to just a few days in serious cases. The intracellular components of the RBCs are released into the circulating blood and into tissues, leading to some of the characteristic symptoms of this condition. The antibodies are usually directed against high-incidence antigens, therefore they also commonly act on allogenic RBCs. AIHA is a relatively rare condition, with an incidence of 5–10 cases per 1 million persons per year in the warm-antibody type and 0.45 to 1.9 cases per 1 million persons per year in the cold antibody type. Autoimmune hemolysis might be a precursor of later onset systemic lupus erythematosus.

<span class="mw-page-title-main">Citrullination</span> Biological process

Citrullination or deimination is the conversion of the amino acid arginine in a protein into the amino acid citrulline. Citrulline is not one of the 20 standard amino acids encoded by DNA in the genetic code. Instead, it is the result of a post-translational modification. Citrullination is distinct from the formation of the free amino acid citrulline as part of the urea cycle or as a byproduct of enzymes of the nitric oxide synthase family.

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<span class="mw-page-title-main">YWHAH</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Anti–citrullinated protein antibody</span> Autoantibodies

Anti-citrullinated protein antibodies (ACPAs) are autoantibodies that are directed against peptides and proteins that are citrullinated. They are present in the majority of patients with rheumatoid arthritis. Clinically, cyclic citrullinated peptides (CCP) are frequently used to detect these antibodies in patient serum or plasma.

<span class="mw-page-title-main">Autoimmune disease</span> Disorders of adaptive immune system

An autoimmune disease is a condition that results from an anomalous response of the adaptive immune system, wherein it mistakenly targets and attacks healthy, functioning parts of the body as if they were foreign organisms. It is estimated that there are more than 80 recognized autoimmune diseases, with recent scientific evidence suggesting the existence of potentially more than 100 distinct conditions. Nearly any body part can be involved.

<span class="mw-page-title-main">Anti-dsDNA antibodies</span> Group of anti-nuclear antibodies

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Anti-histone antibodies are autoantibodies that are a subset of the anti-nuclear antibody family, which specifically target histone protein subunits or histone complexes. They were first reported by Henry Kunkel, H.R. Holman, and H.R.G. Dreicher in their studies of cellular causes of lupus erythematosus in 1959–60. Today, anti-histone antibodies are still used as a marker for systemic lupus erythematosus, but are also implicated in other autoimmune diseases like Sjögren syndrome, dermatomyositis, or rheumatoid arthritis. Anti-histone antibodies can be used as a marker for drug-induced lupus.

Cold sensitive antibodies (CSA) are antibodies sensitive to cold temperature. Some cold sensitive antibodies are pathological and can lead to blood disorder. These pathological cold sensitive antibodies include cold agglutinins, Donath–Landsteiner antibodies, and cryoglobulins which are the culprits of cold agglutinin disease, paroxysmal cold hemoglobinuria in the process of Donath–Landsteiner hemolytic anemia, and vasculitis, respectively.

References

  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. ↑ [ full citation needed ]
  13. ↑ The Arthritis Association, Report by MHC 19.2
  14. 1 2 3 4 "Rheumatoid factor - Mayo Clinic". Mayo Clinic .
  15. 1 2 3 4 5 6 7 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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