Anti–Cyclic Citrullinated Peptide Antibodies in the Diagnosis of Rheumatoid Arthritis: Bayes Clears the Haze

In this issue, Nishimura and colleagues review the value of testing for anti–cyclic citrullinated peptide (CCP) antibodies in the diagnosis of rheumatoid arthritis (1). Their well-done meta-analysis confirms that the presence of anti-CCP antibody is more specific than rheumatoid factor for diagnosing rheumatoid arthritis and thereby corroborates the results of 2 published systematic reviews (2, 3).

The biology of this putative biomarker of rheumatoid arthritis is intriguing. Anti-CCP antibodies may be important in the pathoetiology of rheumatoid arthritis. A specific interaction between smoking and certain HLA-DR4 genes exists in patients with rheumatoid arthritis who test positive for anti-CCP antibodies (4), and anti-CCP antibodies worsened arthritis in a murine model of arthritis (5). Healthy persons with anti-CCP antibodies are more likely than those without these antibodies to develop rheumatoid arthritis (6, 7). Rheumatoid arthritis varies phenotypically, from mild joint inflammation at 1 end of the spectrum to progressive, severe joint destruction with extra-articular manifestations, such as the Felty syndrome, keratoconjunctivitis sicca, interstitial lung disease, and rheumatoid vasculitis, at the other. Anti-CCP antibodies seem to define a rheumatoid arthritis phenotype that is characterized by extensive structural joint damage (1, 2), functional impairment (8), and disease that is more likely to benefit from very early antirheumatic therapy (9).

Once viewed as inexorably progressive, rheumatoid arthritis has become a potentially curable disease with early, aggressive use of disease-modifying antirheumatic drugs (DMARDs). Therefore, early and accurate diagnosis has become increasingly important (10) …