Diagnostic and clinical value of anti-citrullinated cyclic peptide antibodies in rheumatoid arthritis

ABSTRACT

Antibodies directed to citrulline-containing proteins have been shown to be specific for rheumatoid arthritis [RA]. They may be related to disease activity and extent of joint damage. To investigate the value of anti-citrullinated cyclic peptide antibodies [anti-CCP] in diagnosis and clinical evaluation of RA patients compared with rheumatoid factor [RF] isotypes [IgG-, IgA- and IgM-RF. In a cross-sectional study, anti-CCP and RF isotypes were assayed by ELISA in 44 RA patients, 25 patients with arthritis other than RA and 15 healthy controls. RA disease activity was assessed as mild [18 patients], moderate [15 patients] or severe [11 patients] using DAS 28 score. Bone involvement in RA was classified radiologically [recent radiographs for hands and wrists] into 3 categories no bone involvement [16 patients], juxta-articular osteoporosis [13 patients] or joint erosions [15 patients]. According to disease duration, those with duration less than one year were grouped as early RA [17 patients] and those with duration more than one year as established RA [27 patients]. Sensitivity of anti-CCP was 72.7%; non significantly different [p>0.05] from those of IgM-RF [63.6%] or cumulative RF isotypes [75%] and significantly higher [p<0.05] than IgA- [47.7%] and IgG-RF [36.4%]. Specificity of anti-CCP was 100%; significantly higher [p<0.05] than those of IgA- [92.5%], IgG- [87.5%], IgM-RF [80%] and cumulative RF isotypes [70%]. Positive predictive value of anti-CCP was 100%; significantly higher [p<0.05] than those of IgA- [87.5%], IgM-[77.8%], IgG-RF [76.2%] and cumulative RF isotypes [73.3%]. Negative predictive value of anti-CCP was 76.9%; non significantly different [p>0.05] from those of cumulative RF isotypes [71.8%] or IgM-RF [66.7%] and significantly higher [p<0.05] than those of IgA- [61.7%] and IgG-RF [55.6%]. Anti-CCP positivity in RA patients with bone erosions was 100%; significantly higher [p<0.05] than those of cumulative RF istypes [93.3%], IgM- [86.7%], IgA- [86.7%] and IgG-RF [46.7%]. Anti-CCP positivity in patients with severe disease activity was 90.9%; non significantly higher [p>0.05] than cumulative RF isotypes [81.8%] and significantly higher [p<0.05] than those of IgA- [72.7%], IgM- [54.5%] and IgG-RF [27.3%]. Anti-CCP and RF isotypes positivity in early RA were non significantly different from those in established RA. Of special diagnostic value was the detection of positive anti-CCP in 72.2% [8/11] of RA patients in whom all RF isotypes were negative. This was especially signified in RA patients with bone erosions, severe disease activity or established. Anti-CCP proved to be a powerful diagnostic tool in RA especially in RF negative patients. It can be potentially useful as prognostic index for bone involvement and disease activity