Rheumatoid Factor and Anti Cyclic Citrullinated Peptide Antibodies

The diagnosis of rheumatoid arthritis (RA) is usually made based on clinical findings, supported by laboratory testing. The mainstay of testing has been the IgM rheumatoid factor (RF), which is an autoantibody directed against the Fc portion of the IgG molecule. The sensitivity of RF is approximately 54% to 88% and the specificity 48% to 92%, depending on the method used (Lee and Schur, 2003). RF is not specific for RA and may be detected in the serum of persons with other rheumatoid conditions, chronic infections, or inflammatory conditions, as well as in healthy older adults.

Results are usually reported as a titer determined by using a tube dilution method. A significant titer is 1:80 or greater. In RA, titers are often 1:640 to 1:520 but can even be found up to 1:320,000. Very high titers more likely indicate severe disease or systemic involvement. Increasing serial titer elevations can be used to monitor RA disease progression, but not response to therapy. RF titers may decrease during remission, but only rarely do they become undetectable. The ESR is a better index of disease activity.

Anti-cyclic citrullinated peptide (anti-CCP) antibodies show promise in the diagnosis of RA. Citrulline is an amino acid produced by modification of arginine and is found in filaggrin, a component of keratin. Recently, sensitivity and specificity of anti-CCP antibodies was reported as 67% and 95%, respectively. The advantage of anti-CCP over RF is that it is much more specific for RA. Its optimal use is uncertain, but anti-CCP testing shows greatest benefit with false-positive RF, such as in hepatitis C with cryoglobuline-mia. In patients with a moderate pretest probability of RA, positive anti-CCP significantly increases the likelihood of RA (Shmerling, 2009).

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