Protein microarrays guide tolerizing DNA vaccine treatment of autoimmune encephalomyelitis |
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Authors: | Robinson William H Fontoura Paulo Lee Byung J de Vegvar Henry E Neuman Tom Jennifer Pedotti Rosetta DiGennaro Carla D Mitchell Dennis J Fong Derek Ho Peggy P-K Ruiz Pedro J Maverakis Emanual Stevens David B Bernard Claude C A Martin Roland Kuchroo Vijay K van Noort Johannes M Genain Claude P Amor Sandra Olsson Tomas Utz Paul J Garren Hideki Steinman Lawrence |
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Institution: | Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA. wrobins@stanford.edu |
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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. |
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