In rheumatoid arthritis (RA), the high diagnostic value of serum antibodies to the stratum corneum of rat esophagus epithelium has been widely reported. These so-called "antikeratin antibodies," detected by indirect immunofluorescence, were found to be autoantibodies since they also labeled human epidermis. Despite their name, the actual target of these autoantibodies was not known. In this study, a 40-kD protein (designated as 40K), extracted from human epidermis and specifically immunodetected by 75% of RA sera, was purified and identified as a neutral/acidic isoform of basic filaggrin, a cytokeratin filament-aggregating protein, by peptide mapping studies and by the following evidences: (a) mAbs specific for filaggrin reacted with the 40K protein; (b) the autoantibodies, affinity-purified from RA sera on the 40K protein, immunodetected purified filaggrin; (c) the reactivity of RA sera to the 40K protein was abolished after immunoadsorption with purified filaggrin; (d) the 40K protein and filaggrin had similar amino acid compositions. Furthermore, autoantibodies against the 40K protein and the so-called "antikeratin antibodies" were shown, by immunoadsorption experiments, to be largely the same. The identification of filaggrin as a RA-specific autoantigen could contribute to the understanding of the pathogenesis of this disease and, ultimately, to the development of methods for preventing the autoimmune response. (J. Clin. Invest. 1993.

Objectives-An attempt was made to characterise the antigens recognised by serum IgG antibodies directed to the stratum corneum of rat oesophagus epithelium, the so-called 'antikeratin antibodies', which were shown to be highly specific for rheumatoid arthritis (RA) and thus to have an actual diagnostic value. Methods-Immunoblotting was performed with RA serum samples on different extracts of rat oesophagus epithelium separated by various monodimensional and two dimensional electrophoreses. Results-Three low-salt-soluble antigens sensitive to proteinase K and, therefore, of protein nature were identified. Two proteins, with apparent molecular masses of 210 and 120-90 kilodaltons, shared isoelectric points ranging from 5 8 to 8 5; the third protein exhibited isoelectric points from 4'5 to 7-2 while its molecular mass ranged from 130 to 60 kilodaltons.

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