Diagnostic value of anticyclic citrullinated peptide antibodies in Greek patients with rheumatoid arthritis: association with extra-articular manifestations

Background

In Northern European Caucasian patients with rheumatoid arthritis (RA), anticyclic citrullinated peptide (anti-CCP) antibodies are associated with the HLA-DRB1 shared epitope and are of diagnostic value. In Greek patients with RA the HLA shared epitope was reported in a minority of patients.

Methods

Using an ELISA (CCP2) kit, we tested anti-CCP antibodies in serum samples from 155 Greek patients with RA, 178 patients with other rheumatic diseases and 100 blood donors. We also determined rheumatoid factor (RF) and compared it with anti-CCP antibodies for the area under the curve (AUC), sensitivity, specificity and likelihood ratios. In RA patients we assessed the activity score, and radiographic joint score. Extra-articular manifestations were recorded in an additional 75 RA patients.

Results

The sensitivity of anti-CCP antibodies for RA was 63.2% and the specificity was 95.0%. The respective values of RF were 59.1% and 91.2%. When considered simultaneously, the AUC for anti-CCP antibodies was 0.90 with a 95% CI of 0.87–0.93 and the AUC for RF was 0.71 with a 95% CI of 0.64–0.77. The presence of both antibodies increased specificity to 98.2%. Anti-CCP antibodies were positive in 34.9% of RF-negative RA patients. Anti-CCP antibodies exhibited a correlation with the radiographic joint damage (Spearman correlation coefficient r = 0.27, P = 0.001). Anti-CCP-positive RA patients had increased the swollen joint count and serum CRP concentration compared with anti-CCP-negative RA patients (Mann–Whitney U test, P = 0.01 and P < 0.001, respectively). However, no correlation was found between anti-CCP antibodies and the DAS28 score (r = 0.13, P = 0.12). RA patients with high anti-CCP2 antibodies (>100 IU/ml) were more likely to have extra-articular manifestations.

Conclusion

In Greek patients with RA, anti-CCP2 antibodies exhibit a better diagnostic value than RF. Anti-CCP2 antibodies show a correlation with joint damage whereas high levels of anti-CCP2 antibodies are associated with extra-articular manifestations. Anti-CCP2 antibodies are therefore useful in rheumatology practice.