Intrathecal B-cell activation in LGI1 antibody encephalitis.
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:
03 2020
03 2020
Historique:
received:
05
09
2019
accepted:
23
12
2019
entrez:
8
2
2020
pubmed:
8
2
2020
medline:
7
5
2021
Statut:
epublish
Résumé
To study intrathecal B-cell activity in leucine-rich, glioma-inactivated 1 (LGI1) antibody encephalitis. In patients with LGI1 antibodies, the lack of CSF lymphocytosis or oligoclonal bands and serum-predominant LGI1 antibodies suggests a peripherally initiated immune response. However, it is unknown whether B cells within the CNS contribute to the ongoing pathogenesis of LGI1 antibody encephalitis. Paired CSF and peripheral blood (PB) mononuclear cells were collected from 6 patients with LGI1 antibody encephalitis and 2 patients with other neurologic diseases. Deep B-cell immune repertoire sequencing was performed on immunoglobulin heavy chain transcripts from CSF B cells and sorted PB B-cell subsets. In addition, LGI1 antibody levels were determined in CSF and PB. Serum LGI1 antibody titers were on average 127-fold higher than CSF LGI1 antibody titers. Yet, deep B-cell repertoire analysis demonstrated a restricted CSF repertoire with frequent extensive clusters of clonally related B cells connected to mature PB B cells. These clusters showed intensive mutational activity of CSF B cells, providing strong evidence for an independent CNS-based antigen-driven response in patients with LGI1 antibody encephalitis but not in controls. Our results demonstrate that intrathecal immunoglobulin repertoire expansion is a feature of LGI1 antibody encephalitis and suggests a need for CNS-penetrant therapies.
Identifiants
pubmed: 32029531
pii: 7/2/e669
doi: 10.1212/NXI.0000000000000669
pmc: PMC7051206
pii:
doi:
Substances chimiques
Autoantibodies
0
Intracellular Signaling Peptides and Proteins
0
LGI1 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Wellcome Trust
ID : 104079/Z/14/Z
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG031189
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI142186
Pays : United States
Organisme : NINDS NIH HHS
ID : K02 NS072288
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS092835
Pays : United States
Informations de copyright
Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
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