Protein microarrays guide, tolerizing DNA vaccine treatment of autoimmune encephalomyelitis

William H. Robinson, Paulo Fontoura, Byung J. Lee, Henry E Neuman De Vegvar, Jennifer Tom, Rosetta Pedotti, Carla D. DiGennaro, Dennis J. Mitchell, Derek Fong, Peggy P K Ho, Pedro J. Ruiz, Emanual Michael Maverakis, David B. Stevens, Claude C A Bernard, Roland Martin, Vijay K. Kuchroo, Johannes M. Van Noort, Claude P. Genain, Sandra Amor, Tomas OlssonPaul J. Utz, Hideki Garren, Lawrence Steinman

Research output: Contribution to journalArticlepeer-review

205 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1033-1039
Number of pages7
JournalNature Biotechnology
Volume21
Issue number9
DOIs
StatePublished - Sep 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology

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