ANTI-CYCLIC CITRULLINATED PEPTIDE ANTIBODIES AND RHEUMATOID FACTOR IN THE DIAGNOSIS OF EARLY VERSUS ESTABLISHED RHEUMATOID ARTHRITIS

Background: The diagnosis of rheumatoid arthritis (RA) is based primarily on clinical manifestations. Immunoglobulin (Ig) M isotype of rheumatoid factor (RF) is the most common laboratory assay for the diagnosis of RA, but it lacks specificity for RA. A test with high specificity for RA is the assay for anti-cyclic citrullinated peptide (anti-CCP) antibodies.Objectives: To evaluate the sensitivity and specificity of anti-CCP and IgM RF in early versus established RA and to investigate the presence of anti-CCP in IgM RF negative patients with RA.Methods: This was a prospective study on a total of 159 patients attending the rheumatology clinic of our hospital. In the study were enrolled 114 consecutive patients with the clinical diagnosis of RA, according to the revised classification criteria of the American College of Rheumatology, and 45 patients with the clinical diagnosis of osteoarthritis (OA). Sera from each patient were tested for anti-CCP antibodies by a commercially available enzyme-linked immunosorbent assay (ELISA) kit (Diastat Anti-CCP EIA, Axis-Shield Diagnostics Ltd. UK), and for IgM RF by turbidimetry. Sensitivity and specificity of the tests were evaluated taking the clinical diagnosis as the gold standard. We evaluated the diagnostic sensitivity of anti-CCP antibodies and IgM RF in two groups of RA patients: those with early RA (36 patients diagnosed within the preceding 12 months) and those with established RA (78 patients diagnosed more than 12 months previously).Results: Of the 36 patients with early RA, 15 (41.66%) were IgM RF positive and 20 (55.55%) were anti-CCP positive. Of the 78 patients with established RA, 61 (76.2%) were IgM RF positive and 54 (69.23%) anti-CCP positive. Double positive for IgM RF and anti-CCP were 59 of the 114 RA patients (51.75%). Among the 38 IgM RF negative RA patients, 15 subjects (39.47%) were anti-CCP positive. Among a total of 114 RA patients, 76 (66.66%) were IgM RF positive and 74 (64.91%) were anti-CCP positive. The results among the OA patients were more striking. These patients yielded 11 (24.44%) false positive results for the IgM RF test, compared with 2 (4.4%) false positive results for the anti-CCP test. Thus in the early RA group the sensitivity for IgM RF was 41.66% and for anti-CCP 55.55%. In the established RA group sensitivity for IgM RF was 78.2% and for anti-CCP was 69.23%. For the aggregate of RA patients the sensitivity of IgM RF was 66.66% and that of anti-CCP antibodies was 64.91%. Specificity was significantly higher for anti-CCP antibodies (95.55%) than for IgM RF (75.55%). The combination of anti-CCP antibodies and IgM RF gave the lowest sensitivity (51.75%) but the highest specificity (97.77%).Conclusion: Anti-CCP antibodies appear to be a highly specific marker for RA, as well as an early marker of RA. The sensitivity of anti-CCP assay for the diagnosis of RA in general is equivalent to that of IgM RF. However, in early RA anti-CCP is more sensitive than IgM RF, while in established RA the reverse is true. More than one third (39.47%) of RA patients with negative IgM RF are anti-CCP positive. Hence, although not very sensitive, the anti-CCP assay may be a powerful diagnostic tool, especially in ambiguous cases of early arthritis with negative IgM RF test.Citation: Ann Rheum Dis, volume 64, supplement III, year 2005, page 172Session: Rheumatoid arthritis – Clinical aspects