CSF proteome in multiple sclerosis subtypes related to brain lesion transcriptomes

Abstract To identify markers in the CSF of multiple sclerosis (MS) subtypes, we used a two-step proteomic approach: (i) Discovery proteomics compared 169 pooled CSF from MS subtypes and inflammatory/degenerative CNS diseases (NMO spectrum and Alzheimer disease) and healthy controls. (ii) Next, 299 p...

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Autores principales: Maria L. Elkjaer, Arkadiusz Nawrocki, Tim Kacprowski, Pernille Lassen, Anja Hviid Simonsen, Romain Marignier, Tobias Sejbaek, Helle H. Nielsen, Lene Wermuth, Alyaa Yakut Rashid, Peter Høgh, Finn Sellebjerg, Richard Reynolds, Jan Baumbach, Martin R. Larsen, Zsolt Illes
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:e937c16553044bfc90da330ef33a440f2021-12-02T12:11:45ZCSF proteome in multiple sclerosis subtypes related to brain lesion transcriptomes10.1038/s41598-021-83591-52045-2322https://doaj.org/article/e937c16553044bfc90da330ef33a440f2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83591-5https://doaj.org/toc/2045-2322Abstract To identify markers in the CSF of multiple sclerosis (MS) subtypes, we used a two-step proteomic approach: (i) Discovery proteomics compared 169 pooled CSF from MS subtypes and inflammatory/degenerative CNS diseases (NMO spectrum and Alzheimer disease) and healthy controls. (ii) Next, 299 proteins selected by comprehensive statistics were quantified in 170 individual CSF samples. (iii) Genes of the identified proteins were also screened among transcripts in 73 MS brain lesions compared to 25 control brains. F-test based feature selection resulted in 8 proteins differentiating the MS subtypes, and secondary progressive (SP)MS was the most different also from controls. Genes of 7 out these 8 proteins were present in MS brain lesions: GOLM was significantly differentially expressed in active, chronic active, inactive and remyelinating lesions, FRZB in active and chronic active lesions, and SELENBP1 in inactive lesions. Volcano maps of normalized proteins in the different disease groups also indicated the highest amount of altered proteins in SPMS. Apolipoprotein C-I, apolipoprotein A-II, augurin, receptor-type tyrosine-protein phosphatase gamma, and trypsin-1 were upregulated in the CSF of MS subtypes compared to controls. This CSF profile and associated brain lesion spectrum highlight non-inflammatory mechanisms in differentiating CNS diseases and MS subtypes and the uniqueness of SPMS.Maria L. ElkjaerArkadiusz NawrockiTim KacprowskiPernille LassenAnja Hviid SimonsenRomain MarignierTobias SejbaekHelle H. NielsenLene WermuthAlyaa Yakut RashidPeter HøghFinn SellebjergRichard ReynoldsJan BaumbachMartin R. LarsenZsolt IllesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Maria L. Elkjaer
Arkadiusz Nawrocki
Tim Kacprowski
Pernille Lassen
Anja Hviid Simonsen
Romain Marignier
Tobias Sejbaek
Helle H. Nielsen
Lene Wermuth
Alyaa Yakut Rashid
Peter Høgh
Finn Sellebjerg
Richard Reynolds
Jan Baumbach
Martin R. Larsen
Zsolt Illes
CSF proteome in multiple sclerosis subtypes related to brain lesion transcriptomes
description Abstract To identify markers in the CSF of multiple sclerosis (MS) subtypes, we used a two-step proteomic approach: (i) Discovery proteomics compared 169 pooled CSF from MS subtypes and inflammatory/degenerative CNS diseases (NMO spectrum and Alzheimer disease) and healthy controls. (ii) Next, 299 proteins selected by comprehensive statistics were quantified in 170 individual CSF samples. (iii) Genes of the identified proteins were also screened among transcripts in 73 MS brain lesions compared to 25 control brains. F-test based feature selection resulted in 8 proteins differentiating the MS subtypes, and secondary progressive (SP)MS was the most different also from controls. Genes of 7 out these 8 proteins were present in MS brain lesions: GOLM was significantly differentially expressed in active, chronic active, inactive and remyelinating lesions, FRZB in active and chronic active lesions, and SELENBP1 in inactive lesions. Volcano maps of normalized proteins in the different disease groups also indicated the highest amount of altered proteins in SPMS. Apolipoprotein C-I, apolipoprotein A-II, augurin, receptor-type tyrosine-protein phosphatase gamma, and trypsin-1 were upregulated in the CSF of MS subtypes compared to controls. This CSF profile and associated brain lesion spectrum highlight non-inflammatory mechanisms in differentiating CNS diseases and MS subtypes and the uniqueness of SPMS.
format article
author Maria L. Elkjaer
Arkadiusz Nawrocki
Tim Kacprowski
Pernille Lassen
Anja Hviid Simonsen
Romain Marignier
Tobias Sejbaek
Helle H. Nielsen
Lene Wermuth
Alyaa Yakut Rashid
Peter Høgh
Finn Sellebjerg
Richard Reynolds
Jan Baumbach
Martin R. Larsen
Zsolt Illes
author_facet Maria L. Elkjaer
Arkadiusz Nawrocki
Tim Kacprowski
Pernille Lassen
Anja Hviid Simonsen
Romain Marignier
Tobias Sejbaek
Helle H. Nielsen
Lene Wermuth
Alyaa Yakut Rashid
Peter Høgh
Finn Sellebjerg
Richard Reynolds
Jan Baumbach
Martin R. Larsen
Zsolt Illes
author_sort Maria L. Elkjaer
title CSF proteome in multiple sclerosis subtypes related to brain lesion transcriptomes
title_short CSF proteome in multiple sclerosis subtypes related to brain lesion transcriptomes
title_full CSF proteome in multiple sclerosis subtypes related to brain lesion transcriptomes
title_fullStr CSF proteome in multiple sclerosis subtypes related to brain lesion transcriptomes
title_full_unstemmed CSF proteome in multiple sclerosis subtypes related to brain lesion transcriptomes
title_sort csf proteome in multiple sclerosis subtypes related to brain lesion transcriptomes
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/e937c16553044bfc90da330ef33a440f
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