Diagnostic impact of contemporary biomarker assays for rheumatoid arthritis

Objective: The impetus towards early treatment for patients with rheumatoid arthritis (RA) requires more reliable disease markers than the non-specific immunoglobulin M(IgM) rheumatoid factor (RF). To determine the accuracy of newer biomarkers for RA testing for antibody against cyclic citrullinated peptides (anti-CCP Ab), IgA- and IgG-RF, and cartilage oligomeric matrix protein (COMP) levels, measured by enzyme-linked immunosorbent assay (ELISA), were compared with IgM-RF isotyping. Methods: Serum samples were investigated in patients with an established diagnosis of RA (n=54), ankylosing spondylitis (AS) (n=36), and non-inflammatory conditions (n=18) (cohort A), and in 234 consecutive outpatients in a blinded fashion (cohort B). Non-parametric analysis of areas under the curve (AUC) of receiver operator characteristics were performed. Results: The presence of anti-CCP Ab had the highest accuracy (96%) in distinguishing RA patients in cohort A and cohort B (accuracy 83%), and in both cohorts combined (accuracy 87%). This was related to the high specificity of anti-CCP Ab for RA (95-96%), even though IgM-RF was the most sensitive test (87-96%). Sensitivity (15-48%) and specificity (66-69%) of COMP as a marker for RA was low. Combining results of anti-CCP Ab and IgM-RF or any of the other assays did not increase the diagnostic accuracy for RA. Conclusion: The presence of anti-CCP Ab is the most accurate biomarker for RA in both selected and unselected cohorts, while the COMP assay is not very useful in RA diagnosis. Combining assays for anti-CCP Ab and IgM-RF or IgA-RF does not enhance RA diagnosis.