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Identification of brain antigens recognized by autoantibodies in experimental autoimmune encephalomyelitis-induced animals treated with etomoxir or interferon-β

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  • Anne Skøttrup Mørkholt, Aalborg University
  • ,
  • Kenneth Kastaniegaard, Aalborg University
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  • Michael Sloth Trabjerg, Aalborg University
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  • Gopana Gopalasingam, Aalborg University
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  • Wanda Niganze, Aalborg University
  • ,
  • Agnete Larsen
  • Allan Stensballe
  • Søren Nielsen, Aalborg University
  • ,
  • John DIrk Nieland, Aalborg University

Multiple sclerosis (MS) is a neurodegenerative autoimmune disease, where chronic inflammation plays an essential role in its pathology. A feature of MS is the production of autoantibodies stimulated by an altered-peptide-ligand response and epitope spreading, resulting in loss of tolerance for self-proteins. The involvement of autoantibodies in MS pathogenesis has been suggested to initiate and drive progression of inflammation; however, the etiology of MS remains unknown. The effect of etomoxir and interferon-β (IFN-β) was examined in an experimental-autoimmune-encephalomyelitis (EAE) model of MS. Moreover, the impact of etomoxir and IFN-β on recognition of brain proteins in serum from EAE rats was examined with the purpose of identifying the autoantibody reactivities involved in MS. Animals treated with etomoxir on day 1 exhibited a statistically significantly lower disease score than animals treated with IFN-β (on day 1 or 5) or placebo. Etomoxir treatment on day 5 resulted in a significantly lower disease score than IFN-β treatment on day 1. After disease induction antibodies was induced to a broad pallet of antigens in the brain. Surprisingly, by blocking CPT1 and therewith lipid metabolism several alterations in the antibody response was observed suggesting that autoantibodies play a role in the EAE animal model.

Original languageEnglish
Article number7092
JournalScientific Reports
Volume8
Issue1
ISSN2045-2322
DOIs
Publication statusPublished - 1 Dec 2018

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