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Copy number variations across the blood-brain barrier in multiple sclerosis. | LitMetric

Copy number variations across the blood-brain barrier in multiple sclerosis.

Ann Clin Transl Neurol

Department of Clinical Neuroscience and Centrum for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.

Published: July 2022

AI Article Synopsis

Article Abstract

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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268884PMC
http://dx.doi.org/10.1002/acn3.51573DOI Listing

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