Editing Rheumatoid factor

{{Short description|Autoantibody found in rheumatoid arthritis}}
{{Distinguish|Rhesus factor}}

'''Rheumatoid factor''' ('''RF''') is the [[autoantibody]] that was first found in [[rheumatoid arthritis]]. It is defined as an [[antibody]] against the [[Fragment crystallizable region|Fc]] portion of [[IgG]] and different RFs can recognize different parts of the IgG-Fc.<ref>{{cite journal|last1=Falkenburg|first1=W.J.J.|title=IgG Subclass Specificity Discriminates Restricted IgM Rheumatoid Factor Responses From More Mature Anti–Citrullinated Protein Antibody–Associated or Isotype-Switched IgA Responses|journal=Arthritis & Rheumatology|date=November 2015|volume=67|issue=12|pages=3124–3134|doi=10.1002/art.39299|pmid=26246004|ref=IgG Subclass Specificity Discriminates Restricted IgM Rheumatoid Factor Responses From More Mature Anti–Citrullinated Protein Antibody–Associated or Isotype-Switched IgA Responses|doi-access=free}}</ref> RF and IgG join to form [[immune complex]]es that contribute to the [[disease]] process such as chronic inflammation and joint destruction at the [[Synovial membrane|synovium]] and [[cartilage]].<ref>{{cite journal |vauthors=Edkins A, Cushley W | year = 2012 | title = The Jekyll and Hyde nature of antibodies | journal = Biological Sciences Review | volume = 25 | issue = 2| page = 4 }}</ref>

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

Although ''predominantly'' encountered as IgM, rheumatoid factor can be of any [[isotype (immunology)|isotype]] of [[immunoglobulins]]; i.e., IgA, IgG, IgM,<ref>{{cite journal |pmid=3775335 |year=1986 |last1=Hermann |first1=E |last2=Vogt |first2=P |last3=Müller |first3=W |title=Rheumatoid factors of immunoglobulin classes IgA, IgG and IgM: Methods of determination and clinical value |volume=116 |issue=38 |pages=1290–7 |journal=Schweizerische Medizinische Wochenschrift}}</ref> IgE,<ref>{{cite journal |pmid=1669588 |year=1991 |last1=Herrmann |first1=D |last2=Jäger |first2=L |last3=Hein |first3=G |last4=Henzgen |first4=M |last5=Schlenvoigt |first5=G |title=IgE rheumatoid factor. Occurrence and diagnostic importance in comparison with IgM rheumatoid factor and circulating immune complexes |volume=1 |issue=5 |pages=302–7 |journal=Journal of Investigational Allergology & Clinical Immunology}}</ref> IgD.<ref>{{cite journal |pmid=1418183 |year=1992 |last1=Banchuin |first1=N |last2=Janyapoon |first2=K |last3=Sarntivijai |first3=S |last4=Parivisutt |first4=L |title=Re-evaluation of ELISA and latex agglutination test for rheumatoid factor detection in the diagnosis of rheumatoid arthritis |volume=10 |issue=1 |pages=47–54 |journal=Asian Pacific Journal of Allergy and Immunology}}</ref>

==Testing==
RF is tested by collecting blood in a plain tube (5&nbsp;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 [[erythrocyte]]s. 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 [[symptom]]s, it can play a role in both diagnosis and disease [[prognosis]]. It is part of the usual disease criteria of [[rheumatoid arthritis]].<ref>{{EMedicine|article|331715|Rheumatoid Arthritis|workup}}</ref>

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 [[serology|serological]] markers for autoimmunity.<ref>{{cite journal |doi=10.1159/000013304 |title=Serological Markers of Autoimmunity in Renal Transplant Patients with Chronic Hepatitis C |year=1998 |last1=Rostaing |first1=Lionel |last2=Modesto |first2=Anne |last3=Cisterne |first3=Jean Marc |last4=Izopet |first4=Jacques |last5=Oksman |first5=Françoise |last6=Duffaut |first6=Michel |last7=Abbal |first7=Michel |last8=Durand |first8=Dominique |journal=American Journal of Nephrology |volume=18 |pages=50–6 |pmid=9481439 |issue=1|s2cid=6941129 }}</ref> The sensitivity of RF for established rheumatoid arthritis is only 60 to 70 percent with a specificity of 78 percent.<ref>{{cite journal|last1=Nishimura|first1=K|last2=Sugiyama|first2=D|last3=Kogata|first3=Y|last4=Tsuji|first4=G|last5=Nakazawa|first5=T|last6=Kawano|first6=S|last7=Saigo|first7=K|last8=Morinobu|first8=A|last9=Koshiba|first9=M|last10=Kuntz|first10=KM|last11=Kamae|first11=I|last12=Kumagai|first12=S|title=Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis.|journal=Annals of Internal Medicine|date=5 June 2007|volume=146|issue=11|pages=797–808|pmid=17548411|doi=10.7326/0003-4819-146-11-200706050-00008|s2cid=6640507}}</ref>

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.<ref> 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. </ref> RF positivity at baseline has also been described as a good prognostic marker for future radiographic damage.<ref> 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. </ref>

==Interpretation==
High levels of rheumatoid factor (in general, above 20&nbsp;[[International unit|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 50-70% of primary forms of disease).<ref name=sd49>[http://www.patient.co.uk/showdoc/40026049/ Rheumatoid Factor - Patient UK]</ref> The higher the level of RF the greater the probability of destructive articular disease.{{citation needed|date=September 2014}} 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]].<ref>[http://www.medicinenet.com/rheumatoid_factor/article.htm] {{full citation needed|date=November 2012}}</ref><ref>[http://www.arthriticassociation.org.uk/research/diet_arthritis_research_5 The Arthritis Association], Report by MHC 19.2</ref>

Other than in [[rheumatoid arthritis]], rheumatoid factor may also be elevated in other conditions, including:
* [[Systemic lupus erythematosus]] (SLE)<ref name="mayo">{{Cite web | url=https://www.mayoclinic.org/tests-procedures/rheumatoid-factor/about/pac-20384800 | title=Rheumatoid factor - Mayo Clinic| website=[[Mayo Clinic]]}}</ref><ref name=mnt>{{cite web | last=Johnson | first=Jon | title=Rheumatoid factor: Ranges, tests, and treatment | website=Medical News Today | date=21 July 2021 | url=https://www.medicalnewstoday.com/articles/325505 | access-date=13 May 2022}}</ref>
* [[Sjögren syndrome]]<ref name="mayo"/><ref name=mnt/>
* [[Hepatitis B]] and [[Hepatitis C|C]],<ref>{{Cite journal|date=2017-03-01|title=Vasculitic syndromes in hepatitis C virus: A review|journal=Journal of Advanced Research|language=en|volume=8|issue=2|pages=99–111|doi=10.1016/j.jare.2016.11.002|issn=2090-1232|doi-access=free|last1=Ragab|first1=Gaafar|last2=Hussein|first2=Mohamed A.|pmid=28149646|pmc=5272950}}</ref> [[herpes]], [[HIV]], and other viral infections<ref name=mnt/>
* [[Primary biliary cirrhosis]]<ref name=mnt/>
* [[Infectious mononucleosis]] and any chronic viral infection<ref name="mayo"/>
* [[Leprosy]]<ref>{{cite journal |last1=Garcia-De La Torre |first1=Ignacio|date=1993 |title=Autoimmune phenomena in leprosy, particularly antinuclear antibodies and rheumatoid factor. |journal=The Journal of Rheumatology |volume=20 |issue=5 |pages=900–3 |pmid=8336322 }}</ref>
* [[Sarcoidosis]]<ref name="mayo"/>
* [[Tuberculosis]], [[syphilis]] and other chronic bacterial infections<ref name=mnt/>
* [[Visceral leishmaniasis]]<ref>{{cite journal |last1=Atta |first1=AM |title=Serum markers of rheumatoid arthritis in visceral leishmaniasis: rheumatoid factor and anti-cyclic citrullinated peptide antibody. |journal= Journal of Autoimmunity|volume= 28|issue= 1|pages= 55–8|doi= 10.1016/j.jaut.2006.12.001|pmid=17257811 |year=2007 |url=http://repositorio.ufba.br/ri/handle/ri/14732 }}</ref>
* [[Malaria]] and other parasitic infections<ref name=mnt/>
* [[Cancer]]<ref name=mnt/>

==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.<ref>{{cite journal |doi=10.1111/j.1699-0463.1940.tb01475.x |title=On the Occurrence of a Factor in Human Serum Activating the Specific Agglutination of Sheep Blood Corpuscles |year=2009 |last1=Waaler |first1=Erik |journal=Acta Pathologica et Microbiologica Scandinavica |volume=17 |issue=2 |pages=172–188}} reproduced in {{cite journal |doi=10.1111/j.1600-0463.2007.apm_682a.x |title=On the Occurrence of a Factor in Human Serum Activating the Specific Agglutintion of Sheep Blood Corpuscles |year=2007 |journal=APMIS |volume=115 |issue=5 |pages=422–38; discussion 439 |pmid=17504400 |last1=Waaler |first1=E|s2cid=221426678 }}</ref><ref>{{cite journal |pmid=18863659 |year=1948 |last1=Rose |first1=HM |last2=Ragan |first2=C |title=Differential agglutination of normal and sensitized sheep erythrocytes by sera of patients with rheumatoid arthritis |volume=68 |issue=1 |pages=1–6 |journal=Proceedings of the Society for Experimental Biology and Medicine |doi=10.3181/00379727-68-16375|s2cid=36340687 }}</ref>

==References==
{{Reflist|30em}}

==External links==
* [https://medlineplus.gov/ency/article/003548.htm RF] on MedlinePlus
* [http://www.labtestsonline.org/understanding/analytes/rheumatoid/test.html ''Rheumatoid Factor''] on Lab Tests Online
* {{eMedicine|article|2087091|Rheumatoid Factor}}
* [https://www.webmd.com/rheumatoid-arthritis/rheumatoid-factor-test Rheumatoid Factor] on WebMD

{{Autoantibodies}}

{{DEFAULTSORT:Rheumatoid Factor}}
[[Category:Autoantibodies]]
[[Category:Rheumatology]]