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. Enzyme-linked immunosorbent assay (ELISA) can differentiate between the different subtypes.
When to measure
Any patient who is suspected of having rheumatoid disease. However, keep in mind it may be negative in rheumatoid disease and thus it is important to refer before serology is available. Many patients with rheumatoid disease are seronegative to begin with but 80% seroconvert (become positive). Disease severity is often worse in those who are seropositive.
How to measure
Venous blood is taken in a 'clotted' tube - usually the 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 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%.
When is it positive
- Rheumatoid arthritis - sensitivity in established disease is only 60-70% with a specificity of 78%. 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.
- 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.
- Juvenile rheumatoid arthritis.
- Healthy individuals (5% increasing to 20% over the age of 65 years).
Prognostic use of rheumatoid factor
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]
One study in Denmark found that people with elevated rheumatoid factor have up to 26-fold greater long-term risk of rheumatoid arthritis, and up to 32% 10-year absolute risk of rheumatoid arthritis.
Further reading and references
Wilson D; Rheumatoid factors in patients with rheumatoid arthritis. Can Fam Physician. 2006 Feb52:180-1.
Rheumatoid arthritis in adults: management; NICE Clinical Guideline (February 2009)
Pincus T; Advantages and limitations of quantitative measures to assess rheumatoid arthritis - joint counts, radiographs, laboratory tests, and patient. Bull Hosp Jt Dis. 200664(1-2):32-9.
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 3146(4):464-70.
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 5146(11):797-808.
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 Jan65(1):35-9. Epub 2005 Jun 23.
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 Feb64(2):299-302. Epub 2004 May 27.
Nielsen SF, Bojesen SE, Schnohr P, et al; Elevated rheumatoid factor and long term risk of rheumatoid arthritis: a prospective cohort study. BMJ. 2012 Sep 6345:e5244. doi: 10.1136/bmj.e5244.
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 Aug42(8):939-46. Epub 2003 Apr 16.