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

Autor: Mørkholt AS; Department of Health Science and Technology, Aalborg University, Aalborg, Denmark., Kastaniegaard K; Department of Health Science and Technology, Aalborg University, Aalborg, Denmark., Trabjerg MS; Department of Health Science and Technology, Aalborg University, Aalborg, Denmark., Gopalasingam G; Department of Health Science and Technology, Aalborg University, Aalborg, Denmark., Niganze W; Department of Health Science and Technology, Aalborg University, Aalborg, Denmark., Larsen A; Department of Biomedicine, Aarhus University, Aarhus, Denmark., Stensballe A; Department of Health Science and Technology, Aalborg University, Aalborg, Denmark., Nielsen S; Department of Health Science and Technology, Aalborg University, Aalborg, Denmark., Nieland JD; Department of Health Science and Technology, Aalborg University, Aalborg, Denmark. jdn@hst.aau.dk.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2018 May 04; Vol. 8 (1), pp. 7092. Date of Electronic Publication: 2018 May 04.
DOI: 10.1038/s41598-018-25391-y
Abstrakt: 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.
Databáze: MEDLINE