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Copy number variations across the blood–brain barrier in multiple sclerosis

OBJECTIVE: Multiple sclerosis (MS) is a neuroinflammatory disease where immune cells cross the blood–brain barrier (BBB) into the central nervous system (CNS). What predisposes these immune cells to cross the BBB is still unknown. Here, we examine the possibility that genomic rearrangements could pr...

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Autores principales: Bedri, Sahl Khalid, Evertsson, Björn, Khademi, Mohsen, Al Nimer, Faiez, Olsson, Tomas, Hillert, Jan, Glaser, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268884/
https://www.ncbi.nlm.nih.gov/pubmed/35560551
http://dx.doi.org/10.1002/acn3.51573
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author Bedri, Sahl Khalid
Evertsson, Björn
Khademi, Mohsen
Al Nimer, Faiez
Olsson, Tomas
Hillert, Jan
Glaser, Anna
author_facet Bedri, Sahl Khalid
Evertsson, Björn
Khademi, Mohsen
Al Nimer, Faiez
Olsson, Tomas
Hillert, Jan
Glaser, Anna
author_sort Bedri, Sahl Khalid
collection PubMed
description OBJECTIVE: Multiple sclerosis (MS) is a neuroinflammatory disease where immune cells cross the blood–brain barrier (BBB) into the central nervous system (CNS). What predisposes these immune cells to cross the BBB is still unknown. Here, we examine the possibility that genomic rearrangements could predisposespecific immune cells in the peripheral blood to cross the BBB and form sub‐populations of cells involved in the inflammatory process in the CNS. METHODS: We compared copy number variations in paired peripheral blood mononuclear cells (PBMCs) and cerebrospinal fluid (CSF) cells from MS patients. Thereafter, using next generation sequencing, we studied the T‐cell receptor beta (TRB) locus rearrangements and profiled the αβ T cell repertoire in peripheral CD4(+) and CD8(+) T cells and in the CSF. RESULTS: We identified deletions in the T‐cell receptor alpha/delta (TRA/D), gamma (TRG), and TRB loci in CSF cells compared to PBMCs. Further characterization revealed diversity of the TRB locus which was used to describe the character and clonal expansion of T cells in the CNS. T‐cell repertoire profiling from either side of the BBB concluded that the most frequent clones in the CSF samples are unique to an individual. Furthermore, we observed a difference in the proportion of expanded T‐cell clones when comparing samples from MS patients in relapse and remission with opposite trends in CSF and peripheral blood. INTERPRETATION: This study provides a characterization of the T cells in the CSF and might indicate a role of expanded clones in MS pathogenicity.
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spelling pubmed-92688842022-07-14 Copy number variations across the blood–brain barrier in multiple sclerosis Bedri, Sahl Khalid Evertsson, Björn Khademi, Mohsen Al Nimer, Faiez Olsson, Tomas Hillert, Jan Glaser, Anna Ann Clin Transl Neurol Research Articles OBJECTIVE: Multiple sclerosis (MS) is a neuroinflammatory disease where immune cells cross the blood–brain barrier (BBB) into the central nervous system (CNS). What predisposes these immune cells to cross the BBB is still unknown. Here, we examine the possibility that genomic rearrangements could predisposespecific immune cells in the peripheral blood to cross the BBB and form sub‐populations of cells involved in the inflammatory process in the CNS. METHODS: We compared copy number variations in paired peripheral blood mononuclear cells (PBMCs) and cerebrospinal fluid (CSF) cells from MS patients. Thereafter, using next generation sequencing, we studied the T‐cell receptor beta (TRB) locus rearrangements and profiled the αβ T cell repertoire in peripheral CD4(+) and CD8(+) T cells and in the CSF. RESULTS: We identified deletions in the T‐cell receptor alpha/delta (TRA/D), gamma (TRG), and TRB loci in CSF cells compared to PBMCs. Further characterization revealed diversity of the TRB locus which was used to describe the character and clonal expansion of T cells in the CNS. T‐cell repertoire profiling from either side of the BBB concluded that the most frequent clones in the CSF samples are unique to an individual. Furthermore, we observed a difference in the proportion of expanded T‐cell clones when comparing samples from MS patients in relapse and remission with opposite trends in CSF and peripheral blood. INTERPRETATION: This study provides a characterization of the T cells in the CSF and might indicate a role of expanded clones in MS pathogenicity. John Wiley and Sons Inc. 2022-05-13 /pmc/articles/PMC9268884/ /pubmed/35560551 http://dx.doi.org/10.1002/acn3.51573 Text en © 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Bedri, Sahl Khalid
Evertsson, Björn
Khademi, Mohsen
Al Nimer, Faiez
Olsson, Tomas
Hillert, Jan
Glaser, Anna
Copy number variations across the blood–brain barrier in multiple sclerosis
title Copy number variations across the blood–brain barrier in multiple sclerosis
title_full Copy number variations across the blood–brain barrier in multiple sclerosis
title_fullStr Copy number variations across the blood–brain barrier in multiple sclerosis
title_full_unstemmed Copy number variations across the blood–brain barrier in multiple sclerosis
title_short Copy number variations across the blood–brain barrier in multiple sclerosis
title_sort copy number variations across the blood–brain barrier in multiple sclerosis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268884/
https://www.ncbi.nlm.nih.gov/pubmed/35560551
http://dx.doi.org/10.1002/acn3.51573
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