RT Journal Article
SR Electronic
T1 Intrathecal B-cell activation in LGI1 antibody encephalitis
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e669
DO 10.1212/NXI.0000000000000669
VO 7
IS 2
A1 Lehmann-Horn, Klaus
A1 Irani, Sarosh R.
A1 Wang, Shengzhi
A1 Palanichamy, Arumugam
A1 Jahn, Sarah
A1 Greenfield, Ariele L.
A1 Dandekar, Ravi
A1 Lepennetier, Gildas
A1 Michael, Sophia
A1 Gelfand, Jeffrey M.
A1 Geschwind, Michael D.
A1 Wilson, Michael R.
A1 Zamvil, Scott S.
A1 von Büdingen, H.-Christian
YR 2020
UL http://nn.neurology.org/content/7/2/e669.abstract
AB 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.BBB=blood-brain barrier; BCR=B-cell receptor; cDNA=complementary DNA; DIRS=deep B-cell immune repertoire sequencing; IgD=immunoglobulin D; IgG=immunoglobulin G; IgM=immunoglobulin M; LGI1=leucine-rich, glioma-inactivated 1; NMDAR=NMDA receptor; PB=peripheral blood; SHM=somatic hypermutation; SM=switched memory; UCSF=University of California, San Francisco; VH=heavy chain variable region