Journal
NATURE BIOTECHNOLOGY
Volume 21, Issue 9, Pages 1033-1039Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nbt859
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Funding
- NHLBI NIH HHS [N01 HV 28183] Funding Source: Medline
- NIAID NIH HHS [AI51614, AI50865, AI50864] Funding Source: Medline
- NIAMS NIH HHS [K08 AR02133, AR49328] Funding Source: Medline
- NIDDK NIH HHS [U19 DK61934, DK61934] Funding Source: Medline
- NINDS NIH HHS [5R01NS18235] Funding Source: Medline
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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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