title: Identification of citrullinated eukaryotic translation initiation factor 4G1 as novel autoantigen in rheumatoid arthritis.
abstract: Antibodies against citrullinated proteins are highly specific for rheumatoid arthritis. We previously reported that functional variants of the gene encoding peptidylarginine deiminase type 4 were closely associated with RA. The purpose of this study was to investigate the citrullinated autoantigens recognized by serum samples from patients with RA. The human chondrocyte cDNA expression library was citrullinated by PADI4 and was immunoscreened with anti-modified citrulline antibodies and sera from patients with rheumatoid arthritis. One immunoreactive cDNA clone containing a 2480-base pair insert was isolated and sequence analysis revealed that the cDNA included a part of the eukaryotic translation initiation factor 4G1. Immunoreactivity against a recombinant citrullinated eIF4G1 fragment was observed with high specificity in 50.0% of RA patients. The levels of antibodies against citrullinated eIF4G1 were correlated with those of anti-CCP antibodies. Citrullinated eIF4G1 was identified as a candidate citrullinated autoantigen in RA patients. Citrullination of eIF4G1 may thus be involved in the pathogenesis of RA.
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okazaki
authors.forename: Akari
authors.initials: A
authors.lastname: Suzuki
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Sawada
authors.forename: Miyako
authors.initials: M
authors.lastname: Ohtake-Yamanaka
authors.forename: Tetsufumi
authors.initials: T
authors.lastname: Inoue
authors.forename: Terumitsu
authors.initials: T
authors.lastname: Hasebe
authors.forename: Ryo
authors.initials: R
authors.lastname: Yamada
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*; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D001483:Base Sequence; D002956:Citrulline / Q000276:immunology*; D039603:Eukaryotic Initiation Factor-4G / Q000032:analysis* / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data
chemical_list: D001324:Autoantigens; C113920:EIF4G1 protein, human; D039603:Eukaryotic Initiation Factor-4G; D002956:Citrulline