title: Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein.
abstract: The role of autoantibodies in the pathogenesis of multiple sclerosis (MS) and other demyelinating diseases is controversial, in part because widely used western blotting and ELISA methods either do not permit the detection of conformation-sensitive antibodies or do not distinguish them from conformation-independent antibodies. We developed a sensitive assay based on self-assembling radiolabeled tetramers that allows discrimination of antibodies against folded or denatured myelin oligodendrocyte glycoprotein (MOG) by selective unfolding of the antigen domain. The tetramer radioimmunoassay (RIA) was more sensitive for MOG autoantibody detection than other methodologies, including monomer-based RIA, ELISA or fluorescent-activated cell sorting (FACS). Autoantibodies from individuals with acute disseminated encephalomyelitis (ADEM) selectively bound the folded MOG tetramer, whereas sera from mice with experimental autoimmune encephalomyelitis induced with MOG peptide immunoprecipitated only the unfolded tetramer. MOG-specific autoantibodies were identified in a subset of ADEM but only rarely in adult-onset MS cases, indicating that MOG is a more prominent target antigen in ADEM than MS.
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: O'Connor
authors.forename: Katherine A
authors.initials: KA
authors.lastname: McLaughlin
authors.forename: Philip L
authors.initials: PL
authors.lastname: De Jager
authors.forename: Tanuja
authors.initials: T
authors.lastname: Chitnis
authors.forename: Estelle
authors.initials: E
authors.lastname: Bettelli
authors.forename: Chenqi
authors.initials: C
authors.lastname: Xu
authors.forename: William H
authors.initials: WH
authors.lastname: Robinson
authors.forename: Sunil V
authors.initials: SV
authors.lastname: Cherry
authors.forename: Amit
authors.initials: A
authors.lastname: Bar-Or
authors.forename: Brenda
authors.initials: B
authors.lastname: Banwell
authors.forename: Hikoaki
authors.initials: H
authors.lastname: Fukaura
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Fukazawa
authors.forename: Silvia
authors.initials: S
authors.lastname: Tenembaum
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Wong
authors.forename: Norma P
authors.initials: NP
authors.lastname: Tavakoli
authors.forename: Zhannat
authors.initials: Z
authors.lastname: Idrissova
authors.forename: Vissia
authors.initials: V
authors.lastname: Viglietta
authors.forename: Kevin
authors.initials: K
authors.lastname: Rostasy
authors.forename: Daniela
authors.initials: D
authors.lastname: Pohl
authors.forename: Russell C
authors.initials: RC
authors.lastname: Dale
authors.forename: Mark
authors.initials: M
authors.lastname: Freedman
authors.forename: Lawrence
authors.initials: L
authors.lastname: Steinman
authors.forename: Guy J
authors.initials: GJ
authors.lastname: Buckle
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Kuchroo
authors.forename: David A
authors.initials: DA
authors.lastname: Hafler
authors.forename: Kai W
authors.initials: KW
authors.lastname: Wucherpfennig
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000302:isolation & purification* / Q000378:metabolism; D004673:Encephalomyelitis, Acute Disseminated / Q000097:blood / Q000276:immunology*; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D051379:Mice; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology* / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D017510:Protein Folding; D012680:Sensitivity and Specificity
chemical_list: D001323:Autoantibodies; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein