Cross-reactivity of a pathogenic autoantibody to a tumor antigen in GABA A receptor encephalitis.

Fecha de publicación:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Brändle SM
  • Cerina M
  • Weber S
  • Held K
  • Menke AF
  • Gebert D
  • Herrmann AM
  • Pellkofer H
  • Gerdes LA
  • Bittner S
  • Leypoldt F
  • Teegen B
  • Komorowski L
  • Kümpfel T
  • Hohlfeld R
  • Meuth SG
  • Melzer N
  • Beltrán E
  • Dornmair K

Grupos

Abstract

Encephalitis associated with antibodies against the neuronal gamma-aminobutyric acid A receptor (GABA A -R) is a rare form of autoimmune encephalitis. The pathogenesis is still unknown but autoimmune mechanisms were surmised. Here we identified a strongly expanded B cell clone in the cerebrospinal fluid of a patient with GABA A -R encephalitis. We expressed the antibody produced by it and showed by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry that it recognizes the GABA A -R. Patch-clamp recordings revealed that it tones down inhibitory synaptic transmission and causes increased excitability of hippocampal CA1 pyramidal neurons. Thus, the antibody likely contributed to clinical disease symptoms. Hybridization to a protein array revealed the cross-reactive protein LIM-domain-only protein 5 (LMO5), which is related to cell-cycle regulation and tumor growth. We confirmed LMO5 recognition by immunoprecipitation and ELISA and showed that cerebrospinal fluid samples from two other patients with GABA A -R encephalitis also recognized LMO5. This suggests that cross-reactivity between GABA A -R and LMO5 is frequent in GABA A -R encephalitis and supports the hypothesis of a paraneoplastic etiology.

Datos de la publicación

ISSN/ISSNe:
0027-8424, 1091-6490

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA  NATL ACAD SCIENCES

Tipo:
Article
Páginas:
-
PubMed:
33619082
Factor de Impacto:
4,184 SCImago
Cuartil:
Q1 SCImago

Citas Recibidas en Web of Science: 27

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Keywords

  • GABA-A-receptor encephalitis, autoantibody, autoimmune encephalitis, epilepsy, paraneoplastic encephalitis

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