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
- Tipo:
- Article
- Páginas:
- -
- PubMed:
- 33619082
- Factor de Impacto:
- 4,184 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA NATL ACAD SCIENCES
Citas Recibidas en Web of Science: 27
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- No hay documentos
Filiaciones
Keywords
- GABA-A-receptor encephalitis, autoantibody, autoimmune encephalitis, epilepsy, paraneoplastic encephalitis
Portal de investigación