IgG, IgA, IgM antibodies to a viral citrullinated peptide in patients affected by rheumatoid arthritis, chronic arthritides and connective tissue disorders

OBJECTIVES: Anti-citrullinated protein/peptide antibodies (ACPA), a family of antibodies with overlapping specificities, represent a specific marker of rheumatoid arthritis (RA). The aim of the present study is to investigate the prevalence and clinical significance of IgG, IgA and IgM ACPA by a newly described assay employing a viral citrullinated peptide (VCP). METHODS: IgG, IgA and IgM anti-VCP antibodies have been measured in sera from 146 patients affected by RA and 404 controls, including 204 chronic arthritides, 111 connective tissue disorders and 89 healthy subjects. The affinity of the different isotypes for VCP was analysed by liquid phase inhibition assays. RESULTS: Among RA patients, 40 were single positive for IgG anti-VCP, five for IgA and 11 for IgM. Ten patients were double positive for IgG and IgA, four for IgG and IgM, six for IgA and IgM. In 15 RA patients IgG, IgA and IgM anti-VCP antibodies were detected. No correlation could be found between the isotype and the clinical manifestations or duration of the disease. IgA anti-VCP were strongly associated with RA, whereas IgM anti-VCP were detected also in a low percentage of systemic lupus erythematosus, psoriatic arthritis and mixed cryoglobulinaemia (MC) patients. IgG anti-VCP displayed a higher affinity for the antigen than IgA or IgM. CONCLUSIONS: These data show that anti-VCP of IgG and IgA isotype discriminate RA from other chronic arthritides and disease controls and suggest an independent production of each isotype.