Abstract
Filaggrin is expressed in the cornified layer of epidermis and known to be one of the antigenic targets in rheumatoid arthritis. Although the citrulline residue in filaggrin is thought to be an antigenic determinant recognized by autoantibodies, the diagnostic sensitivity of synthetic citrullinated peptide is variable. To investigate the implication of anti-filaggrin antibodies recognizing uncitrullinated filaggrin in rheumatoid arthritis, we assayed antibody titers using unmodified recombinant filaggrin in the sera from 73 patients with rheumatoid arthritis, 150 patients with other connective tissue diseases and 70 normal controls. We also performed the correlation analysis between antibody titers and the clinical variables in patients with rheumatoid arthritis. Titers of IgG anti-filaggrin antibodies were significantly higher in rheumatoid arthritis patients compared to normal controls (P=0.02), but not in patients with osteoarthritis, ankylosing spondylitis or systemic lupus erythematosus. IgG anti-filaggrin antibodies were more frequently found in patients with rheumatoid arthritis compared to normal controls (12.3% vs 1.4% respectively, P=0.04). An anti-filaggrin antibody titer was correlated with visual analogue scale of pain, tender joint count, Ritchie articular index or C-reactive protein, but not with anti-nuclear antibody or rheumatoid factor. These results suggest that anti-filaggrin antibody recognizes the uncitrullinated filaggrin as an antigen and its titer correlates with clinical parameters, explaining the variable sensitivity of anti-filaggrin antibody test.
Highlights
Rheumatoid arthritis (RA) is a chronic inflammatory joint disease affecting around 1% of the general population (Kellgren, 1996)
We report that ELISA using unmodified recombinant filaggrin showed a 12.3% diagnostic sensitivity at a specificity of 95% which was correlated with visual analogue scale of pain, tender joint count, Ritchie articular index or C-reactive protein in RA patients
IgM antifilaggrin antibody (AFA) titer showed no difference between RA patients and normal controls (0.279 ± 0.029 a.u. versus 0.209 ± 0.026 a.u., P = 0.08) (Figure 3B)
Summary
Rheumatoid arthritis (RA) is a chronic inflammatory joint disease affecting around 1% of the general population (Kellgren, 1996). Various serologic markers were suggested to overcome the low specificity of the RF, including Sa, kalpastatin, antikeratin antibody (AKA) and antiperinuclear factor (APF) (Menard et al, 1998). The AKA and APF, which are the antibodies against the cornified epithelium of rat esophagus and human buccal mucosa respectively, are known to be specific for RA (Nienhuis et al, 1964; Young et al, 1979). The antigen targets of both antibodies were suggested to be the same protein which is filaggrin in the human epidermis (Hoet et al, 1991; Simon et al, 1993; Sebbag et al, 1995). Filaggrin monomer is released from profilaggrin and modified by peptidylarginine deiminase which converts the arginine residues found in filaggrin to the citrulline. Modified filaggrin is thought to be interacted and aggregated with the keratin intermediate filaments in keratinocytes, facilitating and guiding their alignment (Berthelot et al, 1995)
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