Risk HLA Variants Affect the T-Cell Repertoire in Multiple Sclerosis.
Journal
Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
received:
02
08
2022
accepted:
14
12
2022
entrez:
15
2
2023
pubmed:
16
2
2023
medline:
18
2
2023
Statut:
epublish
Résumé
The major histocompatibility complex (MHC) locus has a predominant role in the genetic predisposition to multiple sclerosis (MS), with 32 associations found to be involved. We aimed to investigate the impact of MHC MS-risk alleles on T-cell repertoire in patients with MS. We studied 161 untreated patients with relapsing-remitting MS for whom Class I and II human leukocyte antigen (HLA) alleles were inferred from whole-genome genotyping data, and T-cell receptor (TCR) CDR3 sequences were obtained through next-generation sequencing. T-cell repertoire features including diversity, public clones, and architecture were evaluated. We identified 5 MS-risk loci associated with TCR diversity: HLA-DRB1*15:01 (7.65 × 10 Our study supports the association between MHC-risk alleles and macrofeatures of the T-cell repertoire in the context of MS. Further studies are needed to understand the underlying molecular mechanisms.
Sections du résumé
BACKGROUND AND OBJECTIVES
The major histocompatibility complex (MHC) locus has a predominant role in the genetic predisposition to multiple sclerosis (MS), with 32 associations found to be involved. We aimed to investigate the impact of MHC MS-risk alleles on T-cell repertoire in patients with MS.
METHODS
We studied 161 untreated patients with relapsing-remitting MS for whom Class I and II human leukocyte antigen (HLA) alleles were inferred from whole-genome genotyping data, and T-cell receptor (TCR) CDR3 sequences were obtained through next-generation sequencing. T-cell repertoire features including diversity, public clones, and architecture were evaluated.
RESULTS
We identified 5 MS-risk loci associated with TCR diversity: HLA-DRB1*15:01 (7.65 × 10
DISCUSSION
Our study supports the association between MHC-risk alleles and macrofeatures of the T-cell repertoire in the context of MS. Further studies are needed to understand the underlying molecular mechanisms.
Identifiants
pubmed: 36792371
pii: 10/3/e200093
doi: 10.1212/NXI.0000000000200093
pmc: PMC9931183
pii:
doi:
Substances chimiques
HLA-DRB1 Chains
0
Receptors, Antigen, T-Cell
0
HLA Antigens
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
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