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<title>Rheumatoid factor</title>

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Rheumatoid factor

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</style><div role="note" class="hatnote navigation-not-searchable">Not to be confused with <a href="Rhesus_factor" class="mw-redirect" title="Rhesus factor">Rhesus factor</a>.</div>

Rheumatoid factor (RF) is the <a href="Autoantibody" title="Autoantibody">autoantibody</a> that was first found in <a href="Rheumatoid_arthritis" title="Rheumatoid arthritis">rheumatoid arthritis</a>. It is defined as an <a href="Antibody" title="Antibody">antibody</a> against the <a href="Fragment_crystallizable_region" title="Fragment crystallizable region">Fc</a> portion of <a href="IgG" class="mw-redirect" title="IgG">IgG</a> and different RFs can recognize different parts of the IgG-Fc.<a href="#cite_note-1">[1]</a> RF and IgG join to form <a href="Immune_complex" title="Immune complex">immune complexes</a> that contribute to the <a href="Disease" title="Disease">disease</a> process such as chronic inflammation and joint destruction at the <a href="Synovial_membrane" title="Synovial membrane">synovium</a> and <a href="Cartilage" title="Cartilage">cartilage</a>.<a href="#cite_note-2">[2]</a>

Rheumatoid factor can also be a <a href="Cryoglobulin" class="mw-redirect" title="Cryoglobulin">cryoglobulin</a> (antibody that precipitates on cooling of a blood sample); it can be either type 2 (<a href="Monoclonal" class="mw-redirect" title="Monoclonal">monoclonal</a> <a href="IgM" class="mw-redirect" title="IgM">IgM</a> to <a href="Polyclonal" class="mw-redirect" title="Polyclonal">polyclonal</a> IgG) or type 3 (polyclonal IgM to polyclonal IgG) cryoglobulin.

Although predominantly encountered as IgM, rheumatoid factor can be of any <a href="Isotype_(immunology)" title="Isotype (immunology)">isotype</a> of <a href="Immunoglobulins" class="mw-redirect" title="Immunoglobulins">immunoglobulins</a>; i.e., IgA, IgG, IgM,<a href="#cite_note-3">[3]</a> IgE,<a href="#cite_note-4">[4]</a> IgD.<a href="#cite_note-5">[5]</a>

<div class="mw-heading mw-heading2"><h2 id="Testing">Testing</h2></div>

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 <a href="Nephelometry" class="mw-redirect" title="Nephelometry">nephelometry</a>, <a href="Turbidimetry" title="Turbidimetry">turbidimetry</a>, agglutination of gamma globulin-coated latex particles or <a href="Erythrocyte" class="mw-redirect" title="Erythrocyte">erythrocytes</a>. RF is often evaluated in patients suspected of having any form of <a href="Arthritis" title="Arthritis">arthritis</a>, even though positive results can be due to other causes and negative results do not rule out disease. In combination with signs and <a href="Symptom" class="mw-redirect" title="Symptom">symptoms</a>, it can play a role in both diagnosis and disease <a href="Prognosis" title="Prognosis">prognosis</a>. It is part of the usual disease criteria of <a href="Rheumatoid_arthritis" title="Rheumatoid arthritis">rheumatoid arthritis</a>.<a href="#cite_note-6">[6]</a>

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 <a href="Serology" title="Serology">serological</a> markers for autoimmunity.<a href="#cite_note-7">[7]</a> The sensitivity of RF for established rheumatoid arthritis is only 60 to 70 percent with a specificity of 78 percent.<a href="#cite_note-8">[8]</a>

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

<div class="mw-heading mw-heading2"><h2 id="Interpretation">Interpretation</h2></div>

High levels of rheumatoid factor (in general, above 20 <a href="International_unit" title="International unit">IU</a>/mL, 1:40, or over the 95th <a href="Percentile" title="Percentile">percentile</a>; there is some variation among labs) occur in rheumatoid arthritis (present in 80%) and <a href="Sj%C3%B6gren's_syndrome" class="mw-redirect" title="Sjögren's syndrome">Sjögren's syndrome</a> (present in 50-70% of primary forms of disease).<a href="#cite_note-sd49-11">[11]</a> The higher the level of RF the greater the probability of destructive articular disease. It is also found in <a href="Epstein%E2%80%93Barr_virus" title="Epstein–Barr virus">Epstein–Barr virus</a> or <a href="Parvovirus" class="mw-redirect" title="Parvovirus">Parvovirus</a> 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 <a href="Arthritis" title="Arthritis">arthritis</a>.<a href="#cite_note-12">[12]</a><a href="#cite_note-13">[13]</a>

Other than in <a href="Rheumatoid_arthritis" title="Rheumatoid arthritis">rheumatoid arthritis</a>, rheumatoid factor may also be elevated in other conditions, including:

<ul><li><a href="Systemic_lupus_erythematosus" class="mw-redirect" title="Systemic lupus erythematosus">Systemic lupus erythematosus</a> (SLE)<a href="#cite_note-mayo-14">[14]</a><a href="#cite_note-mnt-15">[15]</a></li>

<li><a href="Sj%C3%B6gren_syndrome" class="mw-redirect" title="Sjögren syndrome">Sjögren syndrome</a><a href="#cite_note-mayo-14">[14]</a><a href="#cite_note-mnt-15">[15]</a></li>

<li><a href="Hepatitis_B" title="Hepatitis B">Hepatitis B</a> and <a href="Hepatitis_C" title="Hepatitis C">C</a>,<a href="#cite_note-16">[16]</a> <a href="Herpes" title="Herpes">herpes</a>, <a href="HIV" title="HIV">HIV</a>, and other viral infections<a href="#cite_note-mnt-15">[15]</a></li>

<li><a href="Primary_biliary_cirrhosis" class="mw-redirect" title="Primary biliary cirrhosis">Primary biliary cirrhosis</a><a href="#cite_note-mnt-15">[15]</a></li>

<li><a href="Infectious_mononucleosis" title="Infectious mononucleosis">Infectious mononucleosis</a> and any chronic viral infection<a href="#cite_note-mayo-14">[14]</a></li>

<li><a href="Leprosy" title="Leprosy">Leprosy</a><a href="#cite_note-17">[17]</a></li>

<li><a href="Sarcoidosis" title="Sarcoidosis">Sarcoidosis</a><a href="#cite_note-mayo-14">[14]</a></li>

<li><a href="Tuberculosis" title="Tuberculosis">Tuberculosis</a>, <a href="Syphilis" title="Syphilis">syphilis</a> and other chronic bacterial infections<a href="#cite_note-mnt-15">[15]</a></li>

<li><a href="Visceral_leishmaniasis" title="Visceral leishmaniasis">Visceral leishmaniasis</a><a href="#cite_note-18">[18]</a></li>

<li><a href="Malaria" title="Malaria">Malaria</a> and other parasitic infections<a href="#cite_note-mnt-15">[15]</a></li>

<li><a href="Cancer" title="Cancer">Cancer</a><a href="#cite_note-mnt-15">[15]</a></li></ul>

<div class="mw-heading mw-heading2"><h2 id="History">History</h2></div>

The test was first described by Norwegian Dr <a href="Erik_Waaler" title="Erik Waaler">Erik Waaler</a> in 1940 and redescribed by Dr <a href="Harry_M._Rose" title="Harry M. Rose">Harry M. Rose</a> 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.<a href="#cite_note-19">[19]</a><a href="#cite_note-20">[20]</a>

<div class="mw-heading mw-heading2"><h2 id="References">References</h2></div>

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<li id="cite_note-19"><a href="#cite_ref-19">^</a> <cite id="CITEREFWaaler2009" class="citation journal cs1">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. <a href="Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1111%2Fj.1699-0463.1940.tb01475.x">10.1111/j.1699-0463.1940.tb01475.x</a>.</cite> reproduced in <cite id="CITEREFWaaler2007" class="citation journal cs1">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. <a href="Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1111%2Fj.1600-0463.2007.apm_682a.x">10.1111/j.1600-0463.2007.apm_682a.x</a>. <a href="PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/17504400">17504400</a>. <a href="S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:221426678">221426678</a>.</cite>

</li>

<li id="cite_note-20"><a href="#cite_ref-20">^</a> <cite id="CITEREFRoseRagan1948" class="citation journal cs1">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. <a href="Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.3181%2F00379727-68-16375">10.3181/00379727-68-16375</a>. <a href="PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/18863659">18863659</a>. <a href="S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:36340687">36340687</a>.</cite>

</li>

</ol></div>

<div class="mw-heading mw-heading2"><h2 id="External_links">External links</h2></div>

<ul><li><a rel="nofollow" class="external text" href="https://medlineplus.gov/ency/article/003548.htm">RF</a> on MedlinePlus</li>

<li><a rel="nofollow" class="external text" href="http://www.labtestsonline.org/understanding/analytes/rheumatoid/test.html">Rheumatoid Factor</a> on Lab Tests Online</li>

<li><a rel="nofollow" class="external text" href="https://emedicine.medscape.com/article/2087091-overview">Rheumatoid Factor</a> at <a href="EMedicine" title="EMedicine">eMedicine</a></li>

<li><a rel="nofollow" class="external text" href="https://www.webmd.com/rheumatoid-arthritis/rheumatoid-factor-test">Rheumatoid Factor</a> on WebMD</li></ul>

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</style><div id="Autoantibodies158" style="font-size:114%;margin:0 4em"><a href="Autoantibody" title="Autoantibody">Autoantibodies</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="Anti-nuclear_antibody" class="mw-redirect" title="Anti-nuclear antibody">Anti-nuclear antibody</a></th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em">

<ul><li><a href="Primary_biliary_cirrhosis" class="mw-redirect" title="Primary biliary cirrhosis">PBC</a>:

<ul><li><a href="Extractable_nuclear_antigen" title="Extractable nuclear antigen">ENA</a>:

<ul><li><a href="Anti-topoisomerase_antibodies" title="Anti-topoisomerase antibodies">Anti-topoisomerase/Scl-70</a></li>

<ul><li><a href="Anti-centromere_antibodies" class="mw-redirect" title="Anti-centromere antibodies">Anti-centromere</a></li></ul>

<ul><li><a href="Anti-dsDNA" class="mw-redirect" title="Anti-dsDNA">Anti-dsDNA</a></li></ul>

<ul><li><a href="Anti-histone_antibodies" title="Anti-histone antibodies">Anti-histone</a></li></ul>

</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="Anti-mitochondrial_antibody" title="Anti-mitochondrial antibody">Anti-mitochondrial antibody</a></th><td class="navbox-list-with-group navbox-list navbox-even hlist" style="width:100%;padding:0"><div style="padding:0 0.25em">

<ul><li><a href="Anti-cardiolipin_antibodies" title="Anti-cardiolipin antibodies">Anti-cardiolipin</a></li></ul>

</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Anti-<a href="Cytoplasm" title="Cytoplasm">cytoplasm</a> antibody</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em">

<ul><li><a href="Anti-neutrophil_cytoplasmic_antibody" title="Anti-neutrophil cytoplasmic antibody">Anti-neutrophil cytoplasmic</a>

<li><a href="Anti-smooth_muscle_antibody" title="Anti-smooth muscle antibody">Anti-smooth muscle</a>

<ul><li><a href="Anti-actin_antibodies" title="Anti-actin antibodies">Anti-actin</a></li></ul></li>

<li><a href="Anti-thyroid_peroxidase_antibody" class="mw-redirect" title="Anti-thyroid peroxidase antibody">Anti-TPO/Antimicrosomal</a></li></ul>

</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Cell membrane</th><td class="navbox-list-with-group navbox-list navbox-even hlist" style="width:100%;padding:0"><div style="padding:0 0.25em">

<ul><li><a href="Anti-ganglioside_antibodies" class="mw-redirect" title="Anti-ganglioside antibodies">Anti-ganglioside</a></li>

<li><a href="Anti-glutamate_receptor_antibodies" title="Anti-glutamate receptor antibodies">Anti-glutamate</a></li></ul>

</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Extracellular</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em">

<ul><li><a href="Anti-thrombin_antibodies" title="Anti-thrombin antibodies">Anti-thrombin</a></li>

<li><a href="Lupus_anticoagulant" title="Lupus anticoagulant">Lupus anticoagulant</a></li></ul>

<ul><li><a href="Coeliac_disease" title="Coeliac disease">Coeliac disease</a>:

<ul><li><a href="Anti-transglutaminase_antibodies" title="Anti-transglutaminase antibodies">Anti-transglutaminase</a></li>

<li><a href="Anti-gliadin_antibodies" title="Anti-gliadin antibodies">Anti-gliadin</a> not autoantibody</li></ul></li></ul>

<ul>

<li><a href="Anti%E2%80%93citrullinated_protein_antibody" title="Anti–citrullinated protein antibody">Anti-citrullinated peptide</a></li></ul></li></ul>

</div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Multiple locations</th><td class="navbox-list-with-group navbox-list navbox-even hlist" style="width:100%;padding:0"><div style="padding:0 0.25em">

<ul><li><a href="Antiphospholipid_syndrome" title="Antiphospholipid syndrome">Anti-phospholipid</a></li>

<li><a href="Anti-apolipoprotein_antibodies" title="Anti-apolipoprotein antibodies">Anti-apolipoprotein</a></li></ul>

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This article is issued from <a class="external text" title="Last edited on 2025-05-02" href="https://en.wikipedia.org/wiki/?title=Rheumatoid_factor&oldid=1288467519">Wikipedia</a>. The text is available under <a class="external text" href="https://creativecommons.org/licenses/by-sa/4.0/deed.en">Creative Commons Attribution-Share Alike 4.0</a> unless otherwise noted. Additional terms may apply for the media files.

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