Antiperinuclear factor and antikeratin antibodies (AKA) were shown to belong to the same family of rheumatoid arthritis (RA)-specific autoantibodies directed at 'citrullinated' peptidic epitopes borne by (pro)filaggrins. We showed that their major target in the synovial tissue of RA patients is deiminated (citrullinated) fibrin. Although (pro)filaggrins are probably only cross-reactive proteins, their in vitro detection allowed the development of several highly efficient tests for the diagnosis of RA. Among those, the CCP ELISAs (CCP1 and CCP2), based on a cyclic citrullinated peptide derived from human filaggrin, and the ArFA-ELISA that we developed using a citrullinated recombinant rat filaggrin appear to be the most promising. The rapidly growing interest of rheumatologists in autoantibodies to citrullinated proteins rendered the development of a convenient, fully automated test the next challenge. Based on the ArFA-ELISA, we developed an automated test on the VIDAS machine (bioMérieux), called VIDAS-EDRA (early diagnosis rheumatoid arthritis). Thresholds were defined on a large series of 617 patients with well defined, established rheumatic diseases, including 181 patients with RA. Antibodies to CCP1 and CCP2 (Immunoscan, Eurodiagnostica) were sought following the manufacturer procedures. Rheumatoid factor (RF) and AKA were also analyzed in the series. The diagnostic performances of the tests were compared. In established diseases the diagnostic sensitivity of the VIDAS-EDRA was found to be identical to that of CCP2, and was significantly higher than tests for AKA, CCP1 and RF.
Autoantibodies to citrullinated proteins can be efficiently detected with the highly specific and sensitive automated test VIDAS-EDRA.
Table 1. Diagnostic sensitivity (%) computed at thresholds allowing 95.2% and 98.6% diagnostic specificity to be achieved