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

Abstract 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...

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Autores principales: Anne Skøttrup Mørkholt, Kenneth Kastaniegaard, Michael Sloth Trabjerg, Gopana Gopalasingam, Wanda Niganze, Agnete Larsen, Allan Stensballe, Søren Nielsen, John Dirk Nieland
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spelling oai:doaj.org-article:03ac8250d29948be8bb7fde0685694742021-12-02T16:07:51ZIdentification of brain antigens recognized by autoantibodies in experimental autoimmune encephalomyelitis-induced animals treated with etomoxir or interferon-β10.1038/s41598-018-25391-y2045-2322https://doaj.org/article/03ac8250d29948be8bb7fde0685694742018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25391-yhttps://doaj.org/toc/2045-2322Abstract 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.Anne Skøttrup MørkholtKenneth KastaniegaardMichael Sloth TrabjergGopana GopalasingamWanda NiganzeAgnete LarsenAllan StensballeSøren NielsenJohn Dirk NielandNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Anne Skøttrup Mørkholt
Kenneth Kastaniegaard
Michael Sloth Trabjerg
Gopana Gopalasingam
Wanda Niganze
Agnete Larsen
Allan Stensballe
Søren Nielsen
John Dirk Nieland
Identification of brain antigens recognized by autoantibodies in experimental autoimmune encephalomyelitis-induced animals treated with etomoxir or interferon-β
description Abstract 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.
format article
author Anne Skøttrup Mørkholt
Kenneth Kastaniegaard
Michael Sloth Trabjerg
Gopana Gopalasingam
Wanda Niganze
Agnete Larsen
Allan Stensballe
Søren Nielsen
John Dirk Nieland
author_facet Anne Skøttrup Mørkholt
Kenneth Kastaniegaard
Michael Sloth Trabjerg
Gopana Gopalasingam
Wanda Niganze
Agnete Larsen
Allan Stensballe
Søren Nielsen
John Dirk Nieland
author_sort Anne Skøttrup Mørkholt
title Identification of brain antigens recognized by autoantibodies in experimental autoimmune encephalomyelitis-induced animals treated with etomoxir or interferon-β
title_short Identification of brain antigens recognized by autoantibodies in experimental autoimmune encephalomyelitis-induced animals treated with etomoxir or interferon-β
title_full Identification of brain antigens recognized by autoantibodies in experimental autoimmune encephalomyelitis-induced animals treated with etomoxir or interferon-β
title_fullStr Identification of brain antigens recognized by autoantibodies in experimental autoimmune encephalomyelitis-induced animals treated with etomoxir or interferon-β
title_full_unstemmed Identification of brain antigens recognized by autoantibodies in experimental autoimmune encephalomyelitis-induced animals treated with etomoxir or interferon-β
title_sort identification of brain antigens recognized by autoantibodies in experimental autoimmune encephalomyelitis-induced animals treated with etomoxir or interferon-β
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/03ac8250d29948be8bb7fde068569474
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