In the last years. the detection of antibodies (Abs) against citrullinated peptides (ACPA) has largely replaced rheumatoid factor (RF) as the most helpful biomarker in the diagnosis of rheumatoid arthritis (RA). Current assays detect ACPA reactivity with epitopes on various different citrullinated proteins. Among these, anti-cyclic citrullinated peptide (CCP) Abs have been widely demonstrated to be an important diagnostic and prognostic tool because of their high specificity. Recently, citrullinated vimentin, a protein highly released in synovial microenvironment, has been identified as potential autoantigen in the pathophysiology of RA and an enzyme-linked immunosorbent assay (ELISA) for the detection of Abs directed against a mutated citrullinated vimentin (anti-MCV) was developed. Several recent studies evaluating the characteristics of anti-MCV in comparison to anti-CCP Abs, have given conflicting results. Anti-MCV have been demonstrated to perform better than anti-CCP as predictor of radiographic damage. Conversely, its additional diagnostic and prognostic role in comparison to anti-CCP in both early and established RA is controversial. Aim of this study was to evaluate the diagnostic performance of anti-MCV in RA and to compare it to anti-CCP and the recently developed assay targeting viral citrullinated peptide 2 (VCP2) in a large cohort of RA patients (n = 285), healthy subjects and other disease controls (n = 227). Anti-MCV resulted to have a sensitivity of 59% and a specificity of 92%. In comparison, anti-CCP and anti-VCP2 displayed a sensitivity of 77% and 61% and a specificity of 96% and 95%, respectively. Of interest, at the manufacturer recommended cutoff value of 20 U/mL, a high percentage of healthy subjects as well as Epstein Barr (EBV) and hepatitis C (HCV) virus infected patients resulted anti-MCV positive. In our large cohort of RA patients, anti-MCV demonstrated lower sensitivity than anti-CCP and VCP2 test, thus not allowing to confirm previously published data. Moreover, the high rate of detection in infectious diseases limits its diagnostic value in undifferentiated arthritis. (C) 2012 Elsevier B.V. All rights reserved.