Rheumatoid Factor

oPatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

Rheumatoid factors are antibodies against the Fc portion of IgG (also an antibody). They can belong to any isotype of immunoglobulin - eg, IgM, IgG and IgE - and any of these can be detected in the blood test.[1]

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Any patient who is suspected of having rheumatoid disease. But keep in mind it may be negative in rheumatoid disease and thus it is important to refer before serology is available.[2] Many patients with rheumatoid disease are seronegative to begin with but 80% seroconvert (become positive).[3] Disease severity is often worse in those who are seropositive.[4]

Also see separate articles Rheumatoid Arthritis, Management of Rheumatoid Arthritis and Disease-modifying Anti-rheumatic Drugs (DMARDs).

Venous blood is taken in a 'clotted' tube - usually the same one as U&E.

Results can be reported in titres (normal <1:20) but more commonly as units (normal <23 IU/ml but see local guidelines, as this may vary from laboratory to laboratory.) The sensitivity and specificity of rheumatoid factor for rheumatoid disease is low and thus it is not a good screening test. However, the predictive value of rheumatoid factor in patients with symmetric polyarticular joint swelling is 80%.

  • Rheumatoid arthritis - sensitivity in established disease is only 60-70% with a  specificity of  78%.[5] The higher the level in rheumatoid disease the worse the joint destruction and the greater the chance of systemic involvement.
  • False positives occur in 5% of healthy individuals and in any inflammatory condition - eg, Sjögren's syndrome, systemic lupus erythematous and mixed connective tissue disorder (see table).

Disease associations of rheumatoid factor (sensitivity in brackets)[1][6]

  • Rheumatoid arthritis (60-70%).
  • Sjögren's syndrome (85-95%).
  • Felty's syndrome (>95%).
  • Systemic sclerosis (~30%).
  • Infective endocarditis.
  • Systemic lupus erythematous (~25-35%).
  • Infectious mononucleosis.
  • Hepatitis.
  • Juvenile rheumatoid arthritis.
  • Tuberculosis.
  • Dermatomyositis.
  • Syphilis.
  • HIV.
  • Influenza.
  • Malignancy.
  • Sarcoidosis.
  • Leukaemia.
  • Healthy individuals 5% increasing to 20% over the age of 65 years.

Rheumatoid factor does not generally help in monitoring rheumatoid disease, although it may help with the use of newer agents such as etanercept and infliximab. In patients on etanercept or infliximab and DMARDs the levels of rheumatoid factor reduce, which is associated with reduced clinical disease activity.[7][8]

It can also predict disease outcome in some patients.[1] One example of this is that radiological progression - ie changes in hand X-rays - is worse in those who are seropositive.[9]

Further reading & references

  1. Wilson D; Rheumatoid factors in patients with rheumatoid arthritis. Can Fam Physician. 2006 Feb;52:180-1.
  2. Rheumatoid arthritis: the management of rheumatoid arthritis in adults; NICE Clinical Guideline (February 2009)
  3. Pincus T; Advantages and limitations of quantitative measures to assess rheumatoid arthritis - joint counts, radiographs, laboratory tests, and patient. Bull Hosp Jt Dis. 2006;64(1-2):32-9.
  4. Shin YS, Choi JH, Nahm DH, et al; Rheumatoid factor is a marker of disease severity in Korean rheumatoid arthritis. Yonsei Med J. 2005 Aug 31;46(4):464-70.
  5. Nishimura K, Sugiyama D, Kogata Y, et al; Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis. Ann Intern Med. 2007 Jun 5;146(11):797-808.
  6. Longmore M, Wilkinson IB and Rajagopalan SR (2004): Oxford Handbook of Clinical Medicine, 6th ed, OUP
  7. Chen HA, Lin KC, Chen CH, et al; The effect of etanercept on anti-cyclic citrullinated peptide antibodies and rheumatoid factor in patients with rheumatoid arthritis. Ann Rheum Dis. 2006 Jan;65(1):35-9. Epub 2005 Jun 23.
  8. De Rycke L, Verhelst X, Kruithof E, et al; Rheumatoid factor, but not anti-cyclic citrullinated peptide antibodies, is modulated by infliximab treatment in rheumatoid arthritis. Ann Rheum Dis. 2005 Feb;64(2):299-302. Epub 2004 May 27.
  9. Vittecoq O, Pouplin S, Krzanowska K, et al; Rheumatoid factor is the strongest predictor of radiological progression of rheumatoid arthritis in a three-year prospective study in community-recruited patients. Rheumatology (Oxford). 2003 Aug;42(8):939-46. Epub 2003 Apr 16.

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Gurvinder Rull
Current Version:
Peer Reviewer:
Dr Adrian Bonsall
Last Checked:
02/11/2012
Document ID:
6924 (v3)
© EMIS

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