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Intrathecal B-cell activation in LGI1 antibody encephalitis.
- Author(s): Lehmann-Horn, Klaus;
- Irani, Sarosh R;
- Wang, Shengzhi;
- Palanichamy, Arumugam;
- Jahn, Sarah;
- Greenfield, Ariele L;
- Dandekar, Ravi;
- Lepennetier, Gildas;
- Michael, Sophia;
- Gelfand, Jeffrey M;
- Geschwind, Michael D;
- Wilson, Michael R;
- Zamvil, Scott S;
- von Büdingen, H-Christian
- et al.
Published Web Locationhttps://doi.org/10.1212/nxi.0000000000000669
ObjectiveTo 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.
MethodsPaired 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.
ResultsSerum 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.
ConclusionsOur results demonstrate that intrathecal immunoglobulin repertoire expansion is a feature of LGI1 antibody encephalitis and suggests a need for CNS-penetrant therapies.
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