Anti-citrullinated protein/peptide antibodies (ACPA) represent an important tool for the diagnosis of rheumatoid arthritis (RA) and the presence of multiple ACPA specificities is highly correlated with the evolution towards RA. However, little is known about the association of single specificities with disease manifestations and response to therapy in established RA. The aim of this work is to evaluate in a retrospective study the clinico-serological association of ACPA detected using VCP1 and VCP2 (EBV-derived citrullinated peptides) and HCP1 and HCP2 (histone-H4-derived citrulinated peptides) in established RA.

In 413 RA patients, anti-VCP1, -VCP2, -HCP1, -HCP2 were measured by ELISA. Patients were evaluated for systemic involvement, disease activity/severity, ongoing and past therapies. Data were analyzed by cluster analysis (CA) and principal component analysis (PCA).

Anti-VCP1 were detected in 44% of RA patients; anti-VCP2 in 52%; anti-HCP1 in 46% and anti-HCP2 in 63%. CA and PCA independently demonstrated that ACPA levels are associated with RF positivity, and lung involvement. Subdividing patients in 5 groups according to the number of anti-peptide antibodies, mean antibody level and RF positivity, as well as the frequency of lung involvement, progressively increase in parallel with the number of ACPA specificities.

Higher number/levels of ACPA subtypes is associated with lung involvement but not with erosive disease. Moreover, a broader ACPA repertoire may identify patients treated with biological therapy, probably affected by a more severe disease. In conclusion, ACPA typing might be relevant for a better characterization of some disease features in established RA.