Background The anti-CCP assay identifies antibodies against endogenous citrullinated proteins that are not completely characterized. The histone H4 seems to be a prominent one according to a recent study (1), which found this protein specifically in the immune complexes from synovial fluid of anti-CCP positive RA patients. Only vimentin, among the previously proposed autoantigens, was present in those immune complexes, but its abundance was much lower than that of histone H4. In addition, a citrullinated H4-derived peptide, H4-c39/40, showed marked immunodominance since antibodies directed against this peptide were present in 100% of synovial fluid samples and in 92–94% of anti-CCP positive sera. These frequencies are much larger than the reported with other autoantigens.
Objectives To confirm the immunodominance of the H4-c39/40 peptide in anti-CCP antibodies from RA patients by direct comparison with citrullinated peptides of two other potential autoantigens.
Methods Five hundred and thirteen patients with established RA and 273 healthy controls were included. Antibodies against H4-c39/40, cFibB36–52 and cVim60–75 were evaluated using indirect ELISA. Concordance between positives and negatives was analyzed with the Goodman and Kruskal's gamma coefficient (γ). In addition, Spearman's rank correlation (rs) was used to analyze the correlation between levels of antibody titers.
Results In contrast to the previous report (1), only 68.5% of the anti-CCP positive patients carried anti-H4-c39/40 antibodies. However, this frequency was higher than the observed with the other two peptides, 50.5% of anti-cFibB36–52 and 28.8% of anti-cVim60–75 positive patients. Consequently, a high concordance was found between anti-CCP and anti-H4-c39–40 antibodies (γ =0.95), which was moderately larger than that observed between anti-CCP and anti-cFibB36–52 antibodies (γ =0.86). In addition, anti-H4-c39/40 antibody titers were correlated with anti-CCP titers, but this correlation was similar to the observed between anti-cFibB36–52 and anti-CCP titers (rs =0.34 and 0.33, respectively). The anti-cVim60–75 antibodies, in turn, showed notably low concordance and low correlation with the anti-CCP antibodies.
Conclusions Our results confirm that anti-H4-c39/40 antibodies are a significant component of the antibodies detected with the anti-CCP assay. However, immunodominance of this peptide was not as marked in our patients as the described in the original study.
Meng X, et al. PLoS One. 2016; 11(10):e0165501.
Acknowledgements Funding was provided by grants of the Instituto de Salud Carlos III (Spain) PI14/01561 and RD12/009/008 with participation of FEDER.
Disclosure of Interest None declared