Rheumatoid Factor 

Updated: Mar 16, 2014
  • Author: Tyler Street, MD; Chief Editor: Eric B Staros, MD  more...
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Reference Range

Antibodies directed against the Fc fragment of immunoglobulin G (IgG) are called rheumatoid factors (RFs). They are heterogenous and usually composed of immunoglobulin M (IgM). Because of this, most assays detect only IgM. RFs are used as a marker in individuals with suspected rheumatoid arthritis (RA) or other autoimmune conditions. [1, 2, 3, 4]

The normal reference range for RF is less than 15 IU/mL [5] or less than 1:16. [4]

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Interpretation

Rheumatoid factor (RF) is used in the diagnosis of rheumatoid arthritis (RA). RF results are positive in approximately 75% of patients with RA, although RF is not etiologically related to RA. [6]

High RF titers indicate a poorer prognosis, as patients with higher RF levels tend to have more severe disease. Patients with nodules or clinical evidence of vasculitis usually have positive RF results.

Low levels of RF can even be found in healthy patients, and the test is positive in up to 20% of older individuals. [4]

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Collection and Panels

Collection details are as follows:

  • Specimen type - Serum
  • Container/tube - Red top, gold top or tiger top preferred (gel- bottom tube best, but any serum-type tube adequate)
  • Specimen volume - 1 mL, 0.5 mL minimum [5]
  • Reject specimens in cases of gross lipemia [5]
  • Specimen stability – Refrigerated (preferred) 14 days, ambient 14 days, frozen 14 days
  • Test often included in autoimmune panels

Rheumatoid factor (RF) has historically been measured with all the following assays: Agglutination of sheep RBCs that have been sensitized with rabbit IgG, radioimmunoassays and enzyme immunoassays, and agglutination of polystyrene latex particles coated with human IgG. No assay has been proven to be better than another, and, lack of standardization between tests leads to variability in results.

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Background

Description

Immunoglobulin M (IgM) autoantibodies against the Fc fragment of immunoglobulin G (IgG) are called rheumatoid factors (RFs). These proteins are produced by B cells and can be found circulating in the blood. Their role is unknown in both healthy individuals and in those with rheumatoid arthritis. Approximately 60-80% of individuals with rheumatoid arthritis (RA) have RF present during the course of their disease. However, RF results are positive in less than 40% of patients with early RA. RF levels vary based on disease activity, though even patients with drug-induced remissions generally retain high titers of RF.

RF is also present with other connective-tissue diseases, autoimmune disorders, and proinflammatory states. It is also observed in 1-5% of healthy individuals. Thus, RF is not considered specific for RA.

RF results may be positive in patients without RA who have the following conditions:

Systemic lupus erythematosus

Polymyositis

Tuberculosis

Syphilis

Viral hepatitis

Infectious mononucleosis

Influenza

Indications/Applications

RA is a chronic, autoimmune, peripheral polyarthropathy of unknown etiogenesis. The diagnosis of RA is made via clinical, laboratory, and imaging features, as no test results are pathognomonic. For patients with suspected RA, the following studies are potentially useful:

Considerations

False-negative and false-positive results are common in patients without RA as well as those with RA; patients without RA have an 8% rate of false results, whereas patients with RA have a 15% rate.

RF results may be positive in patients without RA who have the following conditions:

Systemic lupus erythematosus

Polymyositis

Tuberculosis

Syphilis

Viral hepatitis

Infectious mononucleosis

Influenza

Because of its poor specificity and poor positive predictive value, RF is only one test used to diagnose RA and must be ordered judiciously and with purpose. [4]

See Rheumatoid Arthritis: In and Out of the Joint, a Critical Images slideshow, to help identify the distinguishing features of RA as well as the signs of extra-articular manifestations of this disfiguring disease.

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