Similarly, a clear link between antibody production and the degree of inflammation has been shown in patients with SS, as the activity of circulating myeloperoxidase (MPO), which catalyzes the production of cyanate from thiocyanate, seems to be significantly increased [20]. fetal calf serum as the antigen. ACPAs were detected using second-generation ELISA and IgM RF Rabbit Polyclonal to CARD11 was assessed as part of routine analysis. Results Anti-CarP antibodies were detected in 117 patients with RA (34.4%), ACPA in 190 patients (61.4%) and RF in 202 patients (65.3%). Two (2.04%) of the NHS were positive for anti-CarP, one NHS (1.02%) was positive for ACPA and three NHS were positive for RF (3.06%). Among disease controls, anti-CarP antibodies were detected in 33 patients (16.5%), ACPA in 29 patients (14.5%) and RF in 64 patients (32%). In particular, 16.8% of patients with systemic lupus erythematosus and 31.1% of patients with Sj?gren syndrome were positive for anti-CarP. The sensitivity of anti-CarP, ACPA and RF was 46.8%, 61.8% and 64.4%, respectively and specificity was 91.95%, 89.93% and 76.51%, respectively. Conclusions The present study extends the knowledge of anti-CarP antibodies, confirming previous data around the diagnostic accuracy of anti-CarP in RA in a large cohort of Italian patients. Anti-CarP antibodies exhibited relatively low sensitivity and slightly higher specificity compared to ACPA and RF. Even if predominantly present in RA, anti-CarP was detected in a variable percentage of patients with other autoimmune rheumatic diseases WR 1065 and their generation could be attributed to the inflammatory status; the clinical relevance of anti-CarP antibodies in these latter patients should be further decided. Keywords: Rheumatoid arthritis, Autoimmune rheumatic diseases, Systemic lupus erythematosus, Sj?gren syndrome post-translational modifications, Anti-carbamylated proteins antibodies, WR 1065 Anti-citrullinated peptides antibodies, Rheumatoid factor Background The discovery of autoantibodies in patients with RA facilitated the subgrouping of these patients for more accurate therapeutic management, resulting in more efficient disease control [1]. Beside the well-known rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA) have been reported to be a very useful diagnostic and prognostic marker of RA [2]. ACPA have remarkable sensitivity for this disease, with high predictive value for RA development and severity [2, 3]. The importance of ACPA in RA was highlighted by the inclusion of ACPA status in the 2010 classification criteria for RA by allowing the division of patients with RA into two major subsets: WR 1065 ACPA-positive and ACPA-negative [4]. Although ACPA have an important role in the diagnosis of RA, there is still a continuous demand for new biomarkers to further improve the early diagnosis of RA and especially its seronegative subgroup [5]. Recently, a new autoantibody system recognising antibodies against carbamylated proteins (anti-CarP) has been described [6] but has not yet been implemented for commercial use. Initially, Shi et al. identified homocitrulline as the main aminoacid involved in the binding of autoantibodies in seronegative patients with RA [7]. Carbamylation is a chemical reaction mediated by cyanate that modifies lysine residues [5]. Normally the level of cyanate is in equilibrium with urea but specific conditions like inflammation can warp this equilibrium through a myeloperoxidase-dependent mechanism [8, 9]. This leads to the local increase of cyanate levels, thus empowering the degree of carbamylation [10]. Although the high resemblance in structure between citrulline and homocitrulline, inhibition and cohort studies have demonstrated that ACPA and anti-CarP are different and independent antibody subsets that do not cross-react with each other [4, 5]. Unlike ACPA, the presence of anti-CarP has not been associated with HLA-shared epitope (SE) and/or smoking [11]. An interesting finding was the presence of anti-CarP in ACPA-negative patients with RA and their association with WR 1065 increased disease activity [12, 13] and severe joint damage [13, 14]. Moreover, anti-CarP have been detected in patients with arthralgia and their presence has been independently associated with the risk of developing RA [15]. In addition, anti-CarP are present in serum from patients with RA many years before the clinical appearance of the disease [14, 16, 17] and have also been identified in healthy first-degree relatives of patients with RA [18]. Recently, Shi et al. investigated the diagnostic performance of anti-CarP in RA in a large cohort of patients with early arthritis and demonstrated that these antibodies are predominantly detected in RA, but that a small percentage of patients with almost all forms of early arthritis were also anti-CarP-positive [19]. Considering the high prognostic and predictive value that anti-CarP have demonstrated in patients with RA, the aim of this study was to evaluate.