Diagnostic value of anti-cyclic citrullinated peptide antibodies in Greek patients with rheumatoid arthritis

Background: Anti-cyclic citrullinated peptide (anti-CCP) antibodies have been of diagnostic value in Northern European Caucasian patients with rheumatoid arthritis ( RA). In these populations, anti-CCP antibodies are associated with the HLA-DRB1 shared epitope. We assessed the diagnostic value of anti-CCP antibodies in Greek patients with RA where the HLA shared epitope was reported in a minority of patients. Methods: Using an enzyme-linked immunosorbent assay ( 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 to anti-CCP antibodies for area under the curve (AUC), sensitivity, specificity and likelihood ratios. Results: Sensitivity of anti-CCP2 antibodies and RF for RA was 63.2% and 59.1%, and specificity was 95.0% and 91.2%, respectively. When considered simultaneously, the AUC for anti-CCP antibodies was 0.90 with 95% CI of 0.87 to 0.93 and the AUC for RF was 0.71 with 95% CI of 0.64 to 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 showed a correlation with the radiographic joint damage. Anti-CCP-positive RA patients had increased the swollen joint count and serum CRP concentration compared to 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 DAS28 score ( r = 0.13, p = 0.12). Conclusion: In Greek patients with RA, anti-CCP2 antibodies exhibit a better diagnostic value than RF and a correlation with radiological joint damage and therefore are useful in everyday rheumatology practice

Discovery of a new class of inhibitors for the protein arginine deiminase type 4 (PAD4) by structure-based virtual screening

<p>Abstract</p> <p>Background</p> <p>Rheumatoid arthritis (RA) is an autoimmune disease with unknown etiology. Anticitrullinated protein autoantibody has been documented as a highly specific autoantibody associated with RA. Protein arginine deiminase type 4 (PAD4) is the enzyme responsible for catalyzing the conversion of peptidylarginine into peptidylcitrulline. PAD4 is a new therapeutic target for RA treatment. In order to search for inhibitors of PAD4, structure-based virtual screening was performed using LIDAEUS (Ligand discovery at Edinburgh university). Potential inhibitors were screened experimentally by inhibition assays.</p> <p>Results</p> <p>Twenty two of the top-ranked water-soluble compounds were selected for inhibitory screening against PAD4. Three compounds showed significant inhibition of PAD4 and their IC₅₀values were investigated. The structures of the three compounds show no resemblance with previously discovered PAD4 inhibitors, nor with existing drugs for RA treatment.</p> <p>Conclusion</p> <p>Three compounds were discovered as potential inhibitors of PAD4 by virtual screening. The compounds are commercially available and can be used as scaffolds to design more potent inhibitors against PAD4.</p