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)f laggrin 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. (J. Clin. Invest. 1995. 95:2672-2679

The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide

“…Hoet and coworkers (9) described colocalization of APF with a monoclonal antibody specific for the protein (pro)filaggrin in buccal mucosa cells. This finding was confirmed and extended by the biochemical characterization of (pro)filaggrin as the antigen in the APF test and the related so-called antikeratin antibody (AKA) test (12,13), and the APF/ AKA antibodies are therefore more correctly referred to as "antifilaggrin" antibody.…”

Clinical Significance of Anti-CCP Antibodies in Rheumatoid Arthritis

“…They finally demonstrated that this protein was the target antigen of AKA by absorption study, and was a molecule called filaggrin by peptide mapping, which was involved in the aggregation of intracellular cytokeratin filaments. They further recognized that AKA and APF had almost the same specificity, because the target molecule of APF was profilaggrin, the precursor molecule of filaggrin (4).…”

Deiminated Epstein‐Barr virus nuclear antigen 1 is a target of anti–citrullinated protein antibodies in rheumatoid arthritis

“…A clear disease specificity was demonstrated for antiperinuclear factors (APFs) (1) and antikeratin antibodies (AKAs) (2), but for many years the antigen recognized by APFs and AKAs remained unknown. Finally, in 1993, Simon et al (3) showed that the target of AKA is filaggrin, and in 1995 Sebbag et al (4) demonstrated that there was a partial overlap between APFs and AKAs, and that filaggrin-binding IgG was reactive in both the AKA and APF tests.…”