Intrathecal B-cell activation in LGI1 antibody encephalitis

Neurol Neuroimmunol Neuroinflamm. 2020 Feb 6;7(2):e669. doi: 10.1212/NXI.0000000000000669. Print 2020 Mar.


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 types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

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


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