Intrathecal T-cell clonal expansions in patients with multiple sclerosis
File(s)
Author(s)
Type
Journal Article
Abstract
Objective
Analysis of the T-cell receptor (TCR) repertoire in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) can reveal antigen-specific immune responses potentially implicated in the disease process. We applied a new unbiased deep-sequencing method for TCR repertoire analysis to accurately measure and compare receptor diversity and clonal expansions within the peripheral and CSF-trafficking T-cell populations of patients with MS and control individuals with idiopathic intracranial hypertension (IIH).
Methods
Paired blood and CSF TCR β-chain libraries from five MS patients and five IIH controls were sequenced, yielding a total of 80 million reads.
Results
Although TCR repertoire diversity was greater in the blood and CSF compartments of MS patients when compared with IIH controls, it is notable that the frequency of clonal expansions was also significantly higher in both compartments of MS patients. Highly expanded T-cell clones were enriched in the CSF compartment of MS patients compared to peripheral blood, very few of them were detected in both compartments.
Interpretation
Collectively, our data provide a proof of principle that private compartmentalized T-cell expansion exists in the intrathecal space of MS patients.
Analysis of the T-cell receptor (TCR) repertoire in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) can reveal antigen-specific immune responses potentially implicated in the disease process. We applied a new unbiased deep-sequencing method for TCR repertoire analysis to accurately measure and compare receptor diversity and clonal expansions within the peripheral and CSF-trafficking T-cell populations of patients with MS and control individuals with idiopathic intracranial hypertension (IIH).
Methods
Paired blood and CSF TCR β-chain libraries from five MS patients and five IIH controls were sequenced, yielding a total of 80 million reads.
Results
Although TCR repertoire diversity was greater in the blood and CSF compartments of MS patients when compared with IIH controls, it is notable that the frequency of clonal expansions was also significantly higher in both compartments of MS patients. Highly expanded T-cell clones were enriched in the CSF compartment of MS patients compared to peripheral blood, very few of them were detected in both compartments.
Interpretation
Collectively, our data provide a proof of principle that private compartmentalized T-cell expansion exists in the intrathecal space of MS patients.
Date Issued
2016-04-20
Date Acceptance
2016-03-20
Citation
Annals of Clinical and Translational Neurology, 2016, 3 (6), pp.422-433
ISSN
2328-9503
Publisher
Wiley
Start Page
422
End Page
433
Journal / Book Title
Annals of Clinical and Translational Neurology
Volume
3
Issue
6
Copyright Statement
© 2016 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Publication Status
Published