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Epigenetic modulation of AREL1 and increased HLA expression in brains of multiple system atrophy patients

Multiple system atrophy (MSA) is a rare disease with a fatal outcome. To date, little is known about the molecular processes underlying disease development. Its clinical overlap with related neurodegenerative movement disorders underlines the importance for expanding the knowledge of pathological br...

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Autores principales: Rydbirk, Rasmus, Folke, Jonas, Busato, Florence, Roché, Elodie, Chauhan, Alisha Shahzad, Løkkegaard, Annemette, Hejl, Anne-Mette, Bode, Matthias, Blaabjerg, Morten, Møller, Mette, Danielsen, Erik Hvid, Brudek, Tomasz, Pakkenberg, Bente, Tost, Jorg, Aznar, Susana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063795/
https://www.ncbi.nlm.nih.gov/pubmed/32151281
http://dx.doi.org/10.1186/s40478-020-00908-7
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author Rydbirk, Rasmus
Folke, Jonas
Busato, Florence
Roché, Elodie
Chauhan, Alisha Shahzad
Løkkegaard, Annemette
Hejl, Anne-Mette
Bode, Matthias
Blaabjerg, Morten
Møller, Mette
Danielsen, Erik Hvid
Brudek, Tomasz
Pakkenberg, Bente
Tost, Jorg
Aznar, Susana
author_facet Rydbirk, Rasmus
Folke, Jonas
Busato, Florence
Roché, Elodie
Chauhan, Alisha Shahzad
Løkkegaard, Annemette
Hejl, Anne-Mette
Bode, Matthias
Blaabjerg, Morten
Møller, Mette
Danielsen, Erik Hvid
Brudek, Tomasz
Pakkenberg, Bente
Tost, Jorg
Aznar, Susana
author_sort Rydbirk, Rasmus
collection PubMed
description Multiple system atrophy (MSA) is a rare disease with a fatal outcome. To date, little is known about the molecular processes underlying disease development. Its clinical overlap with related neurodegenerative movement disorders underlines the importance for expanding the knowledge of pathological brain processes in MSA patients to improve distinction from similar diseases. In the current study, we investigated DNA methylation changes in brain samples from 41 MSA patients and 37 healthy controls. We focused on the prefrontal cortex, a moderately affected area in MSA. Using Illumina MethylationEPIC arrays, we investigated 5-methylcytosine (5mC) as well as 5-hydroxymethylcytosine (5hmC) changes throughout the genome. We identified five significantly different 5mC probes (adj. P < 0.05), of which one probe mapping to the AREL1 gene involved in antigen presentation was decreased in MSA patients. This decrease correlated with increased 5hmC levels. Further, we identified functional DNA methylation modules involved in inflammatory processes. As expected, the decreased 5mC levels on AREL1 was concordant with increased gene expression levels of both AREL1 as well as MHC Class I HLA genes in MSA brains. We also investigated whether these changes in antigen-related processes in the brain associated with changes in peripheral mononuclear cells. Using flow cytometry on an independent cohort of MSA patients, we identified a decrease in circulating non-classical CD14(+)CD16(++) blood monocytes, whereas T and NK cell populations were unchanged. Taken together, our results support the view of an active neuroimmune response in brains of MSA patients.
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spelling pubmed-70637952020-03-13 Epigenetic modulation of AREL1 and increased HLA expression in brains of multiple system atrophy patients Rydbirk, Rasmus Folke, Jonas Busato, Florence Roché, Elodie Chauhan, Alisha Shahzad Løkkegaard, Annemette Hejl, Anne-Mette Bode, Matthias Blaabjerg, Morten Møller, Mette Danielsen, Erik Hvid Brudek, Tomasz Pakkenberg, Bente Tost, Jorg Aznar, Susana Acta Neuropathol Commun Research Multiple system atrophy (MSA) is a rare disease with a fatal outcome. To date, little is known about the molecular processes underlying disease development. Its clinical overlap with related neurodegenerative movement disorders underlines the importance for expanding the knowledge of pathological brain processes in MSA patients to improve distinction from similar diseases. In the current study, we investigated DNA methylation changes in brain samples from 41 MSA patients and 37 healthy controls. We focused on the prefrontal cortex, a moderately affected area in MSA. Using Illumina MethylationEPIC arrays, we investigated 5-methylcytosine (5mC) as well as 5-hydroxymethylcytosine (5hmC) changes throughout the genome. We identified five significantly different 5mC probes (adj. P < 0.05), of which one probe mapping to the AREL1 gene involved in antigen presentation was decreased in MSA patients. This decrease correlated with increased 5hmC levels. Further, we identified functional DNA methylation modules involved in inflammatory processes. As expected, the decreased 5mC levels on AREL1 was concordant with increased gene expression levels of both AREL1 as well as MHC Class I HLA genes in MSA brains. We also investigated whether these changes in antigen-related processes in the brain associated with changes in peripheral mononuclear cells. Using flow cytometry on an independent cohort of MSA patients, we identified a decrease in circulating non-classical CD14(+)CD16(++) blood monocytes, whereas T and NK cell populations were unchanged. Taken together, our results support the view of an active neuroimmune response in brains of MSA patients. BioMed Central 2020-03-09 /pmc/articles/PMC7063795/ /pubmed/32151281 http://dx.doi.org/10.1186/s40478-020-00908-7 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Rydbirk, Rasmus
Folke, Jonas
Busato, Florence
Roché, Elodie
Chauhan, Alisha Shahzad
Løkkegaard, Annemette
Hejl, Anne-Mette
Bode, Matthias
Blaabjerg, Morten
Møller, Mette
Danielsen, Erik Hvid
Brudek, Tomasz
Pakkenberg, Bente
Tost, Jorg
Aznar, Susana
Epigenetic modulation of AREL1 and increased HLA expression in brains of multiple system atrophy patients
title Epigenetic modulation of AREL1 and increased HLA expression in brains of multiple system atrophy patients
title_full Epigenetic modulation of AREL1 and increased HLA expression in brains of multiple system atrophy patients
title_fullStr Epigenetic modulation of AREL1 and increased HLA expression in brains of multiple system atrophy patients
title_full_unstemmed Epigenetic modulation of AREL1 and increased HLA expression in brains of multiple system atrophy patients
title_short Epigenetic modulation of AREL1 and increased HLA expression in brains of multiple system atrophy patients
title_sort epigenetic modulation of arel1 and increased hla expression in brains of multiple system atrophy patients
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063795/
https://www.ncbi.nlm.nih.gov/pubmed/32151281
http://dx.doi.org/10.1186/s40478-020-00908-7
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