The cytokeratin filament-aggregating protein filaggrin is the target of the so-called "antikeratin antibodies," autoantibodies specific for rheumatoid arthritis.

Abstract

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 autoanti- bodies 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 stud- ies and by the following evidences: (a) mAbs specific for filag- grin reacted with the 40K protein; (b) the autoantibodies, affin- ity-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 filag- grin; (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 dis- ease and, ultimately, to the development of methods for preventing the autoimmune response.(J.Clin.Invest.1993.92:1387-1393.)Key words: autoimmunity * autoantigen * diag- nosis * intermediate filament-associated protein * epidermis was submitted to SDS-PAGE and electrotransferred to immobilon- PVDF membranes (Millipore Corp., Bedford, MA).The 40K protein Antifilaggrin Autoantibodies Specificfor Rheumatoid Arthritis 1387