title: Clinical significance of anti-filaggrin antibody recognizing uncitrullinated filaggrin in rheumatoid arthritis.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Biology/Aging and Apoptosis Research Center, Seoul National University College of Medicine, Seoul 110-799, Korea.
authors.forename: Kyung Ho
authors.initials: KH
authors.lastname: Choi
authors.forename: Eun Bong
authors.initials: EB
authors.lastname: Lee
authors.forename: Chang Dal
authors.initials: CD
authors.lastname: Yoo
authors.forename: Han Joo
authors.initials: HJ
authors.lastname: Baek
authors.forename: Seong Wook
authors.initials: SW
authors.lastname: Kang
authors.forename: Ki Chul
authors.initials: KC
authors.lastname: Shin
authors.forename: Yun Jong
authors.initials: YJ
authors.lastname: Lee
authors.forename: Hyun Ah
authors.initials: HA
authors.lastname: Kim
authors.forename: Ju Hong
authors.initials: JH
authors.lastname: Jeon
authors.forename: Chai Wan
authors.initials: CW
authors.lastname: Kim
authors.forename: Dong Myung
authors.initials: DM
authors.lastname: Shin
authors.forename: In Gyu
authors.initials: IG
authors.lastname: Kim
authors.forename: Yeong Wook
authors.initials: YW
authors.lastname: Son
mesh_terms: D000595:Amino Acid Sequence; D000906:Antibodies / Q000097:blood* / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis* / Q000276:immunology*; D016022:Case-Control Studies; D002956:Citrulline / Q000032:analysis*; D000091344:Filaggrin Proteins; D006801:Humans; D007381:Intermediate Filament Proteins / Q000737:chemistry* / Q000276:immunology* / Q000302:isolation & purification; D008969:Molecular Sequence Data
chemical_list: D000906:Antibodies; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D002956:Citrulline