THE CYTOKERATIN FILAMENT-AGGREGATING PROTEIN FILAGGRIN IS THE TARGET OF THE SO-CALLED ANTIKERATIN ANTIBODIES, AUTOANTIBODIES SPECIFIC FOR RHEUMATOID-ARTHRITIS

In rheumatoid arthritis (RA), the high diagnostic value of serum antib odies to the stratum corneum of rat esophagus epithelium has been wide ly reported. These so-called ''antikeratin antibodies,'' detected by i ndirect immunofluorescence, were found to be autoantibodies since they also labeled human epidermis. Despite their name, the actual target o f these autoantibodies was not known. In this study, a 40-kD protein ( designated as 40K), extracted from human epidermis and specifically im munodetected by 75% of RA sera, was purified and identified as a neutr al / acidic isoform of basic filaggrin, a cytokeratin filament-aggrega ting protein, by peptide mapping studies and by the following evidence s: (a) mAbs specific for filaggrin reacted with the 40K protein; (b) t he autoantibodies, affinity-purified from RA sem on the 40K protein, i mmunodetected purified filaggrin; (c) the reactivity of RA sera to the 40K protein was abolished after immunoadsorption with purified filagg rin; (d) the 40K protein and filaggrin had similar amino acid composit ions. Furthermore, autoantibodies against the 40K protein and the so-c alled ''antikeratin antibodies'' were shown, by immunoadsorption exper iments, to be largely the same. The identification of filaggrin as a R A-specific autoantigen could contribute to the understanding of the pa thogenesis of this disease and, ultimately, to the development of meth ods for preventing the autoimmune response.