N radiological evidence of disease progression and the three other ant…

N radiological evidence of disease progression and the three other antibodies, anti-VCP1, anti-VCP2 and anti-HCP1 antibodies.Discussion We have recently demonstrated that citrullinated histone4 from activated neutrophils and viral citrullinated peptides from Epstein-Barr virus nuclear proteins EBNA1 and 2 are targets for ACPA in sera from patients with RA [14, 18, 19]. In this study, we therefore took the opportunity to investigate further the role of citrullinated-histone-4-derived peptides and EBV-derived peptides in the aetiology of RA, by analysing individuals before the onset Celecoxib of symptoms of RA and by comparing the results with those obtained with anti-CCP2 and citrullinated peptides from alpha-enolase, fibrinogen?chain and filaggrin. Moreover, the association between anti-VCP and antiHCP antibodies and genes conferring predisposition to RA was also investigated. The concentrations of the antibodies against the HCP and VCP antibodies were significantly increased in pre-symptomatic individuals and patients with RA, compared with control subjects. The highest frequency (17.1 ) was found for anti-VCP2 followed by anti-HCP2 antibodies (16.3 ) in pre-symptomatic individuals. The frequency in patients with early RA was 52.3 and 48.5 , which is consistent with previously published studies [13, 15], even if the frequencies reported in those studies were slightly higher, possibly because of the inclusion of patients with an established disease. The majority of the individuals positive for these four antibodies were also anti-CCP2positive. Thus, a small percentage of anti-VCP1- and antiVCP 2-positive and anti-HCP1- and anti-HCP 2-positive individuals were not covered by anti-CCP2 positivity. This evident overlap of anti-CCP2 antibodies with various ACPA is in line with our previous publication [8]. On the contrary, the anti-VCP and anti-HCP antibodies and the three most frequent ACPA, namely antibodies against CEP-1, Fib?6-52 and filaggrin only overlapped to a minor extent, suggesting limited cross-reactivity and/or independent production of these ACPAs. Positivity for one single antibody confers a low risk of development of RA, which increases when more antibody specificities are present together. In fact, the combination of anti-VCP2 and anti-HCP2 antibodies was found toJohansson et al. Arthritis Research Therapy (2016) 18:Page 9 ofincrease the OR to 17.2, but the highest ORs were for anti-VCP1, anti-VCP2 and anti-HCP1, together with antiCCP2 antibodies. The OR for anti-CCP2 antibodies alone was lower in the pre-symptomatic individuals (OR = 21.9). In our previous study the OR was higher for the combination of two ACPA (e.g., anti-CEP1 and anti-Fib36-52 antibodies) (OR = 40.9, 95 CI 19.8, 82.3), although the number of analysed samples from pre-symptomatic individuals and controls were much higher, thus making comparisons on exact values difficult [8]. The major changes that occurred in the distribution of the combinations of anti-CCP2 and anti-VCP1 or anti-VCP2 or anti-HCP1 or anti-HCP2 positivity comparing the pre-symptomatic PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26217556 individuals with the patients after diagnosis was that triple antibody negativity converted to triple antibody positivity. This conversion confirmed that both anti-HCP and antiVCP antibodies appear to play a potential role in the development of RA, e.g., as they display a "classical" ACPA pattern [8]. During the period pre-dating the onset of symptoms the number of positive antibodies increased the closer to.