Diagnostic Performance and Predictive Value of Anti-citrullinated Peptide Antibodies for Diagnosis of Rheumatoid Arthritis: Toward More Accurate Detection?

During the past few years, much enthusiasm has greeted a new laboratory test that measures autoantibodies reactive with synthetic peptides containing the unusual amino acid citrulline, a posttranslationally modified arginine residue (1). Data from several investigators indicated that anti-citrullinated peptide autoantibodies (ACPAs), including anti-cyclic citrullinated peptide (anti-CCP) antibodies, were specifically present in the sera of patients with rheumatoid arthritis (RA); increased specificity is the major advantage of this test (1)(2). Now, in this issue of the Journal, Hoffman et al. (3) prospectively evaluated, in a setting reflecting everyday rheumatologic practice for prevalence of RA, the diagnostic performance of two classic assays for rheumatoid factor (RF) and methods for ACPA detection. Using ROC curve analysis, their study showed that RF has a better overall diagnostic performance than ACPAs. However, when high-specificity cutoffs were selected, one of the ACPA assays (anti-pepA) performed better than RF assays. Importantly, combining one RF assay with one of the ACPA assays increased positive predictive value. Combining one serologic marker with the finding of swollen joints also reveals high positive predictive value.Two of the strengths of their study were that its design reflected everyday rheumatology practice and that the composition of the control group reflected the natural prevalence of diseases in cases for which serologic markers for RA are requested. Their data for specificity, sensitivity, and predictive values are thus easier to interpret. The study included 1003 consecutive patients in situations where the rheumatologist would typically request RF determination. Importantly, diagnoses were established after …