Intrathecal B-cell activation in LGI1 antibody encephalitis.

Abstract

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.

• Authors: Klaus Lehmann-Horn, Sarosh R Irani, Shengzhi Wang, Arumugam Palanichamy, Sarah Jahn, Ariele L Greenfield, Ravi Dandekar, Gildas Lepennetier, Sophia Michael, Jeffrey M Gelfand, Michael D Geschwind, Michael R Wilson, Scott S Zamvil, H-Christian von Büdingen
• Journal: Neurology(R) neuroimmunology & neuroinflammation (Neurol Neuroimmunol Neuroinflamm) Vol. 7 Issue 2 (03 2020) ISSN: 2332-7812 [Electronic] United States
• PMID: 32029531 (Publication Type: 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.)
• Copyright: Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Chemical References

• Autoantibodies
• Intracellular Signaling Peptides and Proteins
• LGI1 protein, human

Topics

• Adult
• Aged
• Autoantibodies (blood, cerebrospinal fluid, metabolism)
• B-Lymphocytes (immunology, metabolism)
• Encephalitis (blood, cerebrospinal fluid, immunology)
• Female
• Humans
• Intracellular Signaling Peptides and Proteins (immunology)
• Male
• Middle Aged