Marked differences in fine specificity and isotype usage of the anti-citrullinated protein antibody in health and disease.

摘要: Objective Anti–citrullinated protein antibodies (ACPAs) display high association with rheumatoid arthritis (RA) and are implicated in its pathogenesis. The presence of ACPAs is known to precede the onset RA. In order identify features that could confer pathogenicity, we extensively characterized this antibody response a unique North American native population patients RA their unaffected relatives. Methods The levels IgA, IgM, IgG ACPAs, as well IgM IgA factor (RF), were measured serum samples obtained from 81 195 relatives. isotype distribution, fine specificity ACPA response, RF compared health disease. Results ACPA positivity was observed 19% healthy relatives ∼91% usage strikingly lower than (1–2 versus 5–6 isotypes). Fine studies showed reactivity citrullinated fibrinogen vimentin present sera RA, while it virtually absent Finally, responses associated but discordant Extended analyses revealed irrespective status, disease relied on interaction ACPAs. Conclusion The qualitatively different disease. Epitope spreading expansion repertoire might be necessary for development facilitated by antibodies.