title: Presence of aberrant VH6 domains in anti-interferon-γ autoantibodies in multiple sclerosis.
abstract: BACKGROUND
  Anti-cytokine autoantibodies (auto-Abs) are ubiquitous both in patients suffering from infectious, inflammatory and autoimmune diseases and in healthy individuals. Particularly anti-IFN-γ auto-Abs are shown to be elevated in blood of multiple sclerosis (MS) patients.
  
  
  OBJECTIVE
  The aim of present study was to investigate whether repertoires of anti-IFN-γ auto-Abs differ in MS patients and healthy donors.
  
  
  METHODS
  Using phage display technique we have compared repertoires of the genes encoding anti-IFN-γ single-chain variable fragments selected from MS and naïve phage display libraries.
  
  
  RESULTS
  The panel of anti-IFN-γ auto-Abs selected from MS library includes (i) 'fetal' auto-Abs, encoded by the VH6-1 gene segment and the combination proximal D segments with distal JH segments; (ii) naïve auto-Abs; (iii) affinity maturated antibodies; and (iv) abnormal single-domain antibodies. Meanwhile, the panel of anti-IFN-γ auto-Abs selected from naïve library mainly contains the naïve antibodies. Moreover, the overall antibody repertoire of MS library is skewed compared to the overall repertoire of naïve library and also contained the antibodies carrying a 'fetal' VH6 domain and the ratio of κ and λ chains was reversed.
  
  
  CONCLUSIONS
  These results suggest existence of a special mechanism or trigger that provides for reconstitution of the immune system in MS.
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia.
authors.forename: Marina A
authors.initials: MA
authors.lastname: Tyumentseva
authors.forename: Vera V
authors.initials: VV
authors.lastname: Morozova
authors.forename: Leonid R
authors.initials: LR
authors.lastname: Lebedev
authors.forename: Igor V
authors.initials: IV
authors.lastname: Babkin
authors.forename: Nina V
authors.initials: NV
authors.lastname: Tikunova
mesh_terms: D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000097:blood / Q000737:chemistry*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000097:blood / Q000737:chemistry*; D007145:Immunoglobulin kappa-Chains / Q000097:blood / Q000737:chemistry*; D007146:Immunoglobulin lambda-Chains / Q000097:blood / Q000737:chemistry*; D007371:Interferon-gamma / Q000097:blood* / Q000276:immunology; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology* / Q000473:pathology; D019151:Peptide Library; D017434:Protein Structure, Tertiary; D017422:Sequence Analysis, DNA; D057127:Single-Chain Antibodies / Q000097:blood / Q000737:chemistry*
chemical_list: D001323:Autoantibodies; D007143:Immunoglobulin Heavy Chains; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D019151:Peptide Library; D057127:Single-Chain Antibodies; D007371:Interferon-gamma
keywords: Immunoglobulin genes; autoantibodies; interferon (IFN)-γ; multiple sclerosis; phage display