The Epitopes Targeted by the Rheumatoid Arthritis-Associated Antifilaggrin Autoantibodies are Posttranslationally Generated on Various Sites of (Pro)Filaggrin by Deimination of Arginine Residues

摘要: Antifilaggrin autoantibodies (AFA) are a population of IgG associated to rheumatoid arthritis (RA), which includes the so-called "antikeratin" Abs and antiperinuclear factor. AFA most specific serological markers RA. We previously showed that they recognize human epidermal filaggrin other profilaggrin-related proteins various epithelial tissues. Here, we report further characterization protein Ags epitopes targeted by AFA. All exhibit numerous neutral/ acidic isoelectric variants were immunochemically demonstrated be deiminated proteins. In vitro deimination recombinant peptidylarginine deiminase generated on protein. Moreover, two three filaggrin-derived synthetic peptides with citrulline in central position specifically widely recognized affinity-purified from series RA sera. These results indicate residues constitutive epitopes, but only context amino acid sequences filaggrin. competition experiments, abolished reactivity sera, showing present major epitopes. data should help identification putative AFA-inducing or cross-reactive articular autoantigen provide new insights into pathogenesis They could also open way toward immunosuppressive and/or preventive therapy