Nodavirus has become a serious pathogen for a wide range of cultured marine fish species. In the present work, the expression of genes related to immune and inflammatory responses of sea bream (Sparus aurata L.), considered as non susceptible species, was studied both in vitro and in vivo. No replication of the virus was observed in head kidney macrophages and blood leukocytes. Moreover, the enhancement of expression of several immune genes (tumor necrosis factor alpha (TNFalpha), interleukin-1-beta (IL-1beta), interferon-induced Mx protein) was not detected in both head kidney macrophages and blood leucocytes in response to an in vitro infection with nodavirus. However, in vivo, nodavirus was detected 1 day post-infection (p.i.) by a reverse transcription-polymerase chain reaction (RT-PCR) in blood, liver, head kidney and brain of experimentally infected sea bream, while its presence clearly decreased in blood after 3 days p.i. Also, a transitory increment of the expression of TNFalpha and IL-1beta was detected in the brain of intramuscular (i.m.) infected sea bream 3 days p.i. In head kidney, the over expression of TNFalpha was only observed 1 day p.i. The expression of Mx, an interferon induced gene, was increased in brain and head kidney of infected sea bream, reaching values of 1300-fold compared to controls in brain three days post-infection. For comparative purposes, we analyzed the expression of the same genes on a susceptible species, such as sea bass (Dicentrarchus labrax) and, although the same pattern of expression was observed both in brain and kidney, the magnitude was different mainly in the case of brain, the key organ of the infection, where higher expression of TNFalpha and lower expression of Mx compared with control was observed.

Objective. To confirm that the presence of anticitrullinated ␣-enolase peptide 1 (anti-CEP-1) antibodies identifies a subgroup of patients with rheumatoid arthritis (RA).Methods. DNA and serum samples were obtained from 451 patients with RA and 279 healthy control subjects, all of whom were of Spanish ancestry. Antibodies to cyclic citrullinated peptide (CCP) and CEP-1 were measured by enzyme-linked immunosorbent assay. HLA-DRB1 and the R620W single-nucleotide polymorphism of PTPN22 were genotyped.Results. Anti-CEP-1 and anti-CCP antibodies were observed in 26.8% and 71.2% of the patients with RA, respectively. Most of the patients (86.6%) with anti-CEP-1 antibodies also had anti-CCP antibodies. Erosive arthritis, rheumatoid factor (RF) positivity, and the presence of the HLA shared epitope (especially the DRB1*04 alleles) were disproportionately associated with the group of patients with both antibodies. In addition, evidence of a significant interaction between the shared epitope and the risk allele of PTPN22 was observed only in these patients. In contrast, the association with these clinical and genetic features was weaker in patients with anti-CCP antibodies but lacking anti-CEP-1 antibodies. These results were obtained in patients in whom the prevalence of RA risk factors differed from that in other previously studied patients.Conclusion. We observed that autoimmunity against citrullinated ␣-enolase may identify a subset of patients with a higher frequency of joint erosions and RF positivity. In addition, we confirmed the disproportionately large effect of the susceptibility alleles of HLA-DRB1 and their interaction with PTPN22 in this subset of patients. These results extend, confirm, and generalize the evidence supporting the specificity of the anti-CEP-1 antibody-positive subgroup of patients with RA among anti-CCP antibody-positive patients with RA.

A large fraction of the patients with rheumatoid arthritis (RA) develop specific autoantibodies, which until recently were only of two types, rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). We aimed to replicate important findings about a recently described third type of specific autoantibodies, anti-carbamylated protein (anti-CarP) antibodies, because they have been described based only in the homemade ELISA from a single laboratory. Our study included 520 patients with established RA and 278 healthy controls of Spanish ancestry and it was done with an independently performed ELISA. The prevalence and pattern of environmental, clinical and genetic associations of the anti-CarP antibodies were similar to the previously described. Notably, the presence and titers of anti-CarP correlated with the presence and titers of ACPA, but the anti-CarP antibodies did not share the known genetic and exposure risk factors of the ACPA. In addition, anti-CarP antibodies were independently associated with a higher (10.5%) prevalence of bone erosions. The reproducibility of these characteristics across laboratories and European subpopulations, indicates the wide validity of the results and suggests that determination of anti-CarP antibodies could contribute to explain RA pathogenesis and identify clinically relevant patient subgroups.

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