title: Protein microarrays guide tolerizing DNA vaccine treatment of autoimmune encephalomyelitis.
abstract: The diversity of autoimmune responses poses a formidable challenge to the development of antigen-specific tolerizing therapy. We developed 'myelin proteome' microarrays to profile the evolution of autoantibody responses in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS). Increased diversity of autoantibody responses in acute EAE predicted a more severe clinical course. Chronic EAE was associated with previously undescribed extensive intra- and intermolecular epitope spreading of autoreactive B-cell responses. Array analysis of autoantigens targeted in acute EAE was used to guide the choice of autoantigen cDNAs to be incorporated into expression plasmids so as to generate tolerizing vaccines. Tolerizing DNA vaccines encoding a greater number of array-determined myelin targets proved superior in treating established EAE and reduced epitope spreading of autoreactive B-cell responses. Proteomic monitoring of autoantibody responses provides a useful approach to monitor autoimmune disease and to develop and tailor disease- and patient-specific tolerizing DNA vaccines.
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA. wrobins@stanford.edu
authors.forename: William H
authors.initials: WH
authors.lastname: Robinson
authors.forename: Paulo
authors.initials: P
authors.lastname: Fontoura
authors.forename: Byung J
authors.initials: BJ
authors.lastname: Lee
authors.forename: Henry E Neuman
authors.initials: HE
authors.lastname: de Vegvar
authors.forename: Jennifer
authors.initials: J
authors.lastname: Tom
authors.forename: Rosetta
authors.initials: R
authors.lastname: Pedotti
authors.forename: Carla D
authors.initials: CD
authors.lastname: DiGennaro
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Mitchell
authors.forename: Derek
authors.initials: D
authors.lastname: Fong
authors.forename: Peggy P-K
authors.initials: PP
authors.lastname: Ho
authors.forename: Pedro J
authors.initials: PJ
authors.lastname: Ruiz
authors.forename: Emanual
authors.initials: E
authors.lastname: Maverakis
authors.forename: David B
authors.initials: DB
authors.lastname: Stevens
authors.forename: Claude C A
authors.initials: CC
authors.lastname: Bernard
authors.forename: Roland
authors.initials: R
authors.lastname: Martin
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Kuchroo
authors.forename: Johannes M
authors.initials: JM
authors.lastname: van Noort
authors.forename: Claude P
authors.initials: CP
authors.lastname: Genain
authors.forename: Sandra
authors.initials: S
authors.lastname: Amor
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Utz
authors.forename: Hideki
authors.initials: H
authors.lastname: Garren
authors.forename: Lawrence
authors.initials: L
authors.lastname: Steinman
mesh_terms: D000818:Animals; D004361:Drug Tolerance; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology*; D007118:Immunoassay / Q000379:methods*; D051379:Mice; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology; D009186:Myelin Sheath / Q000276:immunology*; D040081:Protein Array Analysis / Q000379:methods*; D025941:Protein Interaction Mapping / Q000379:methods; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000276:immunology* / Q000627:therapeutic use*
chemical_list: D019444:Vaccines, DNA