Journal article
Intrathecal B cell activation in LGI1-antibody encephalitis
- Abstract:
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Objective:
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.
Methods:
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.
Results:
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.
Conclusions:
Our results demonstrate that intrathecal immunoglobulin repertoire expansion is a feature of LGI1 antibody encephalitis and suggests a need for CNS-penetrant therapies.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, 899.5KB, Terms of use)
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- Publisher copy:
- 10.1212/NXI.0000000000000669
Authors
- Publisher:
- Lippincott, Williams and Wilkins
- Journal:
- Neurology, Neuroimmunology and Neuroinflammation More from this journal
- Volume:
- 7
- Issue:
- 2
- Article number:
- e669
- Publication date:
- 2020-02-06
- Acceptance date:
- 2019-12-24
- DOI:
- EISSN:
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2332-7812
- Language:
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English
- Keywords:
- Pubs id:
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pubs:1079566
- UUID:
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uuid:04c651ef-cf6d-4539-8ad5-747b9e1e5204
- Local pid:
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pubs:1079566
- Source identifiers:
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1079566
- Deposit date:
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2019-12-24
Terms of use
- Copyright holder:
- Lehmann-Horn et al.
- Copyright date:
- 2020
- Rights statement:
- Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
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