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Rheumatoid Factor

This PatientPlus article is written for healthcare professionals so the language may be more technical than the condition leaflets. You may find the abbreviations list helpful.

Rheumatoid factor is an antibody against the Fc portion of IgG (also an antibody). They can belong to any isotype of immunoglobulin e.g. IgM, IgG and IgE - and any of these can be detected in the blood test.1

When to measure

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

Also see full articles on Rheumatoid Arthritis, Management of Rheumatoid Arthritis and Disease Modifying Antirheumatic Drugs (DMARDs).

How to measure

Venous blood taken in clotted tube - usually same one as U+E.

How are the results reported

Results can be reported in titres (normal < 1:20) but more commonly as units (normal <23 units) (normal levels 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%.

When is it positive

  1. Significant associations - rheumatoid disease, Felty's syndrome. The higher the level in rheumatoid disease the worse the joint destruction and greater the chance of systemic involvement.
  2. Insignificant associations - any inflammatory condition e.g. Sjögrens disease, systemic lupus erythematous and mixed connective tissue disorder (see table).

Disease associations of rheumatoid factor5,1

  • Rheumatoid arthritis 60-70%
  • Sjögrens syndrome ≤100 %
  • Felty's syndrome ≤100 %
  • Systemic sclerosis 30%
  • Infective endocarditis ≤ 50%
  • Systemic lupus erythematous ≤ 40%
  • Infectious mononucleosis
  • Hepatitis
  • Juvenile rheumatoid arthritis
  • Tuberculosis
  • Dermatomyositis
  • Syphillis
  • HIV
  • Influenza
  • Malignancy
  • Sarcoidosis
  • Leukaemia
  • Healthy individuals 1-2% increasing to 20% over age of 65 years

Prognostic use of rheumatoid factor

Rheumatoid factor does not generally help in monitoring disease - although it may help with the use of the newer agents etanercept and infliximab. In patients on etanercept or infliximab and DMARDs the levels of rheumatoid factor reduces, which is associated with reduced clinical disease activity.6,7

It can predict disease outcome in some patients1, one example of this is that radiological progression, i.e. changes in hand X-rays are worse in those who are seropositive.8

Document references

  1. Wilson D; Rheumatoid factors in patients with rheumatoid arthritis. Can Fam Physician. 2006 Feb;52:180-1.
  2. Rheumatoid arthritis, NICE Clinical Guideline (February 2009); Rheumatoid arthritis: the management of rheumatoid arthritis in adults
  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. [abstract]
  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. [abstract]
  5. Longmore, M., Wilkinson, I.B. and Rajagopalan, S.R. (2004): Oxford Handbook of Clinical Medicine, 6th ed, OUP
  6. 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. [abstract]
  7. 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. [abstract]
  8. 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. [abstract]

Acknowledgements

EMIS is grateful to Dr Gurvinder Rull for writing this article. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2009.
Document ID: 6924
Document Version: 2
Document Reference: bgp26049
Last Updated: 18 May 2009
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