title: Anti-citrullinated collagen type I antibody is a target of autoimmunity in rheumatoid arthritis.
abstract: Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, but its autoimmune mechanisms are not clearly understood. Recently, anti-citrullinated peptide antibodies have been specifically observed in sera of RA patients. Furthermore, we identified RA-susceptible variant in a gene encoding citrullinating enzyme, peptidylarginine deiminase type 4 (PADI4). Therefore, we hypothesized that proteins which are modified in RA synovium by PADI4 act as autoantigens. Subsequently, we obtained human collagen type I (huCI) as one of the autoantigens using a RA synoviocyte cDNA library by immunoscreening. We also investigated that the levels of anti-citrullinated huCI were significantly higher in RA patient sera than in normal control sera with high specificity (99%) and positively correlated with the levels of anti-cyclic citrullinated peptide (anti-CCP) antibodies. We concluded that huCI is a novel substrate protein of PADIs and that citrullinated huCI is a candidate autoantigen of RA.
authors.affiliation: Laboratory for Rheumatic Diseases, SNP Research Center, The Institute of Physical and Chemical Research, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Akari
authors.initials: A
authors.lastname: Suzuki
authors.forename: Ryo
authors.initials: R
authors.lastname: Yamada
authors.forename: Miyako
authors.initials: M
authors.lastname: Ohtake-Yamanaka
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okazaki
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Sawada
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D002956:Citrulline / Q000276:immunology; D024042:Collagen Type I / Q000276:immunology*; D005260:Female; D006801:Humans; D006867:Hydrolases / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D000076342:Protein-Arginine Deiminases; D013583:Synovial Membrane / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D024042:Collagen Type I; D002956:Citrulline; D006867:Hydrolases; D000076342:Protein-Arginine Deiminases