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Increased HLA-DR expression and cortical demyelination in MS links with HLA-DR15.
Enz, Lukas Simon; Zeis, Thomas; Schmid, Daniela; Geier, Florian; van der Meer, Franziska; Steiner, Guido; Certa, Ulrich; Binder, Thomas Martin Christian; Stadelmann, Christine; Martin, Roland; Schaeren-Wiemers, Nicole.
Afiliação
  • Enz LS; From the Neurobiology (L.S.E., T.Z., D.S., N.S.-W.), Department of Biomedicine, University Hospital Basel, University Basel, Zentrum für Lehre und Forschung, Switzerland; Department of Biomedicine (F.G.), Bioinformatics Core Facility, University Hospital Basel, Switzerland; SIB Swiss Institute of Bi
  • Zeis T; From the Neurobiology (L.S.E., T.Z., D.S., N.S.-W.), Department of Biomedicine, University Hospital Basel, University Basel, Zentrum für Lehre und Forschung, Switzerland; Department of Biomedicine (F.G.), Bioinformatics Core Facility, University Hospital Basel, Switzerland; SIB Swiss Institute of Bi
  • Schmid D; From the Neurobiology (L.S.E., T.Z., D.S., N.S.-W.), Department of Biomedicine, University Hospital Basel, University Basel, Zentrum für Lehre und Forschung, Switzerland; Department of Biomedicine (F.G.), Bioinformatics Core Facility, University Hospital Basel, Switzerland; SIB Swiss Institute of Bi
  • Geier F; From the Neurobiology (L.S.E., T.Z., D.S., N.S.-W.), Department of Biomedicine, University Hospital Basel, University Basel, Zentrum für Lehre und Forschung, Switzerland; Department of Biomedicine (F.G.), Bioinformatics Core Facility, University Hospital Basel, Switzerland; SIB Swiss Institute of Bi
  • van der Meer F; From the Neurobiology (L.S.E., T.Z., D.S., N.S.-W.), Department of Biomedicine, University Hospital Basel, University Basel, Zentrum für Lehre und Forschung, Switzerland; Department of Biomedicine (F.G.), Bioinformatics Core Facility, University Hospital Basel, Switzerland; SIB Swiss Institute of Bi
  • Steiner G; From the Neurobiology (L.S.E., T.Z., D.S., N.S.-W.), Department of Biomedicine, University Hospital Basel, University Basel, Zentrum für Lehre und Forschung, Switzerland; Department of Biomedicine (F.G.), Bioinformatics Core Facility, University Hospital Basel, Switzerland; SIB Swiss Institute of Bi
  • Certa U; From the Neurobiology (L.S.E., T.Z., D.S., N.S.-W.), Department of Biomedicine, University Hospital Basel, University Basel, Zentrum für Lehre und Forschung, Switzerland; Department of Biomedicine (F.G.), Bioinformatics Core Facility, University Hospital Basel, Switzerland; SIB Swiss Institute of Bi
  • Binder TMC; From the Neurobiology (L.S.E., T.Z., D.S., N.S.-W.), Department of Biomedicine, University Hospital Basel, University Basel, Zentrum für Lehre und Forschung, Switzerland; Department of Biomedicine (F.G.), Bioinformatics Core Facility, University Hospital Basel, Switzerland; SIB Swiss Institute of Bi
  • Stadelmann C; From the Neurobiology (L.S.E., T.Z., D.S., N.S.-W.), Department of Biomedicine, University Hospital Basel, University Basel, Zentrum für Lehre und Forschung, Switzerland; Department of Biomedicine (F.G.), Bioinformatics Core Facility, University Hospital Basel, Switzerland; SIB Swiss Institute of Bi
  • Martin R; From the Neurobiology (L.S.E., T.Z., D.S., N.S.-W.), Department of Biomedicine, University Hospital Basel, University Basel, Zentrum für Lehre und Forschung, Switzerland; Department of Biomedicine (F.G.), Bioinformatics Core Facility, University Hospital Basel, Switzerland; SIB Swiss Institute of Bi
  • Schaeren-Wiemers N; From the Neurobiology (L.S.E., T.Z., D.S., N.S.-W.), Department of Biomedicine, University Hospital Basel, University Basel, Zentrum für Lehre und Forschung, Switzerland; Department of Biomedicine (F.G.), Bioinformatics Core Facility, University Hospital Basel, Switzerland; SIB Swiss Institute of Bi
Neurol Neuroimmunol Neuroinflamm ; 7(2)2020 03.
Article em En | MEDLINE | ID: mdl-31882398
ABSTRACT

OBJECTIVE:

To investigate molecular changes in multiple sclerosis (MS) normal-appearing cortical gray matter (NAGM).

METHODS:

We performed a whole-genome gene expression microarray analysis of human brain autopsy tissues from 64 MS NAGM samples and 42 control gray matter samples. We further examined our cases by HLA genotyping and performed immunohistochemical and immunofluorescent analysis of all human brain tissues.

RESULTS:

HLA-DRB1 is the transcript with highest expression in MS NAGM with a bimodal distribution among the examined cases. Genotyping revealed that every case with the MS-associated HLA-DR15 haplotype also shows high HLA-DRB1 expression and also of the tightly linked HLA-DRB5 allele. Quantitative immunohistochemical analysis confirmed the higher expression of HLA-DRB1 in HLA-DRB1*1501 cases at the protein level. Analysis of gray matter lesion size revealed a significant increase of cortical lesion size in cases with high HLA-DRB1 expression.

CONCLUSIONS:

Our data indicate that increased HLA-DRB1 and -DRB5 expression in the brain of patients with MS may be an important factor in how the HLA-DR15 haplotype contributes to MS pathomechanisms in the target organ.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cadeias HLA-DRB1 / Cadeias HLA-DRB5 / Subtipos Sorológicos de HLA-DR / Substância Cinzenta / Esclerose Múltipla Limite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Neurol Neuroimmunol Neuroinflamm Ano de publicação: 2020 Tipo de documento: Article
Texto completo
Adicionar na Minha BVS
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cadeias HLA-DRB1 / Cadeias HLA-DRB5 / Subtipos Sorológicos de HLA-DR / Substância Cinzenta / Esclerose Múltipla Limite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Neurol Neuroimmunol Neuroinflamm Ano de publicação: 2020 Tipo de documento: Article