title: The antiperinuclear factor and the so-called antikeratin antibodies are the same rheumatoid arthritis-specific autoantibodies.
abstract: The so-called antikeratin antibodies (AKA) and the antiperinuclear factor (APF) are the most specific serological markers of RA. Using indirect immunofluorescence, AKA label the stratum corneum of various cornified epithelia and APF the keratohyalin granules of human buccal mucosa epithelium. We recently demonstrated that AKA recognize human epidermal filaggrin. Here, we report the identification of the major APF antigen as a diffuse protein band of 200-400 kD. This protein is seen to be closely related to human epidermal (pro) filaggrin since it was recognized by four antifilaggrin mAbs specific for different epitopes, and since the APF titers of RA sera were found to be correlated to their AKA titers and to their immunoblotting reactivities to filaggrin. Immunoabsorption of RA sera on purified epidermal filaggrin abolished their reactivities to the granules of buccal epithelial cells and to the 200-400-kD antigen. Moreover, antifilaggrin autoantibodies, i.e., AKA, affinity purified from RA sera, were shown to immunodetect the 200-400-kD antigen and to stain these granules. These results indicate that AKA and APF are largely the same autoantibodies. They recognize human epidermal filaggrin and (pro) filaggrin-related proteins of buccal epithelial cells. Identification of the epitopes recognized by these autoantibodies, which we propose to name antifilaggrin autoantibodies, will certainly open new paths of research into the pathophysiology of RA.
authors.affiliation: Department of Biology and Pathology of the Cell, Toulouse-Purpan School of Medicine, University of Toulouse III, France.
authors.forename: M
authors.initials: M
authors.lastname: Sebbag
authors.forename: M
authors.initials: M
authors.lastname: Simon
authors.forename: C
authors.initials: C
authors.lastname: Vincent
authors.forename: C
authors.initials: C
authors.lastname: Masson-Bessière
authors.forename: E
authors.initials: E
authors.lastname: Girbal
authors.forename: J J
authors.initials: JJ
authors.lastname: Durieux
authors.forename: G
authors.initials: G
authors.lastname: Serre
mesh_terms: D000974:Antibodies, Antinuclear / Q000276:immunology*; D000918:Antibody Specificity; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D015415:Biomarkers; D015153:Blotting, Western; D000091344:Filaggrin Proteins; D005455:Fluorescent Antibody Technique; D006801:Humans; D007381:Intermediate Filament Proteins / Q000276:immunology*; D007633:Keratins / Q000276:immunology*; D008970:Molecular Weight; D009061:Mouth Mucosa / Q000276:immunology
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; C030902:antiperinuclear factor; D007633:Keratins