title: Use of the VH6-1 gene segment to code for anti-interleukin-18 autoantibodies in multiple sclerosis.
abstract: We investigated whether levels and repertoires of anti-interleukin-18 (IL-18) autoantibodies (auto-Abs) differ in multiple sclerosis (MS) patients and healthy donors (HDs). IL-18 concentration in MS patients' sera was higher than in HD, but the level of anti-IL-18 auto-Abs was lower in MS patients. Correlation patterns of IL-18/anti-IL-18 auto-Abs system differed in HD and MS patients, so we have compared segment composition of the anti-IL-18 single-chain variable fragments (scFvs) selected from MS and naïve phage display libraries. Considerable differences between anti-IL-18 auto-Abs of these libraries were found. MS panel contained auto-Abs displaying both signs of "fetal" and somatically hypermutated repertoires. Naïve panel mainly contained the naïve antibodies. These variations from the norm are possible results of abnormal regulation of the repertoire perhaps determined by remodeling of the molecular mechanisms involved in the V(D)J recombination and/or abnormal selection by antigen in MS pathogenesis.
authors.affiliation: Siberian Division of Russian Academy of Sciences, Institute of Chemical Biology and Fundamental Medicine, Novosibirsk, 630090, Russia. vikhrova_m@mail.ru.|The International Biotechnology Center (IBC) "Generium", Volginsky Village, Petushinski District, 601125, Russia. vikhrova_m@mail.ru.
authors.forename: Marina
authors.initials: M
authors.lastname: Tiumentseva
authors.affiliation: Siberian Division of Russian Academy of Sciences, Institute of Chemical Biology and Fundamental Medicine, Novosibirsk, 630090, Russia.
authors.forename: Vera
authors.initials: V
authors.lastname: Morozova
authors.affiliation: Siberian Division of Russian Academy of Sciences, Institute of Chemical Biology and Fundamental Medicine, Novosibirsk, 630090, Russia.
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Zakabunin
authors.affiliation: Regional Centre of MS and Other Autoimmune Diseases of the Nervous System, State Novosibirsk Regional Clinical Hospital, Novosibirsk, 630087, Russia.
authors.forename: Denis
authors.initials: D
authors.lastname: Korobko
authors.affiliation: Regional Centre of MS and Other Autoimmune Diseases of the Nervous System, State Novosibirsk Regional Clinical Hospital, Novosibirsk, 630087, Russia.|Novosibirsk State Medical University, Novosibirsk, 630091, Russia.
authors.forename: Nadezhda
authors.initials: N
authors.lastname: Malkova
authors.affiliation: Siberian Division of Russian Academy of Sciences, Institute of Chemical Biology and Fundamental Medicine, Novosibirsk, 630090, Russia.
authors.forename: Maksim
authors.initials: M
authors.lastname: Filipenko
authors.affiliation: Siberian Division of Russian Academy of Sciences, Institute of Chemical Biology and Fundamental Medicine, Novosibirsk, 630090, Russia.
authors.forename: Nina
authors.initials: N
authors.lastname: Tikunova
mesh_terms: D000293:Adolescent; D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000097:blood / Q000276:immunology; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D020382:Interleukin-18 / Q000097:blood / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology* / Q000473:pathology; D019151:Peptide Library; D057127:Single-Chain Antibodies / Q000235:genetics / Q000276:immunology*; D060152:V(D)J Recombination / Q000235:genetics / Q000276:immunology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D020382:Interleukin-18; D019151:Peptide Library; D057127:Single-Chain Antibodies
keywords: Autoantibodies; Immunoglobulin genes; Interleukin (IL)-18; Multiple sclerosis; Phage display