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

Fecha de publicación: 02/03/2021

Autores de IIS La Fe

María Del Carmen Alcalá Vicente

Autor
Bonaventura Casanova Estruch

Autor

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

Investigación en Neuroinmunología y Esclerosis Múltiple

Leader

Bonaventura Casanova Estruch

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:: -
DOI:: 10.1073/pnas.1916337118
Factor de Impacto:: 4,184 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Métricas

Filiaciones

Brändle SM:: Institute of Clinical Neuroimmunology, Biomedical Center and Hospital of the Ludwig-Maximilians-Universität München, D-82152 Martinsried, Germany
Cerina M:: Department of Neurology, Institute of Translational Neurology, University of Münster, D-48149 Münster, Germany
Weber S:: Institute of Clinical Neuroimmunology, Biomedical Center and Hospital of the Ludwig-Maximilians-Universität München, D-82152 Martinsried, Germany
Held K:: Division of Infectious Diseases and Tropical Medicine, University Hospital, Ludwig Maximilian University of Munich, D-80539 Munich, Germany

German Centre for Infection Research (DZIF), D-80937 Munich, Germany
Menke AF:: Department of Neurology, Institute of Translational Neurology, University of Münster, D-48149 Münster, Germany
Alcalá C:: Neuroimmunology Unit, Hospital Universitari i Politècnic la Fe, 46026 Valencia, Spain
Gebert D:: Institute of Clinical Neuroimmunology, Biomedical Center and Hospital of the Ludwig-Maximilians-Universität München, D-82152 Martinsried, Germany
Herrmann AM:: Department of Neurology, Institute of Translational Neurology, University of Münster, D-48149 Münster, Germany
Pellkofer H:: Institute of Clinical Neuroimmunology, Biomedical Center and Hospital of the Ludwig-Maximilians-Universität München, D-82152 Martinsried, Germany
Gerdes LA:: Institute of Clinical Neuroimmunology, Biomedical Center and Hospital of the Ludwig-Maximilians-Universität München, D-82152 Martinsried, Germany
Bittner S:: Department of Neurology, University of Mainz, D-55131 Mainz, Germany
Leypoldt F:: Institute of Clinical Chemistry, University of Kiel, D-24105 Kiel, Germany

Department of Neurology, University of Kiel, D-24105 Kiel, Germany
Teegen B:: Clinical-Immunological Laboratory Prof. Dr. Stöcker, D-23560 Lübeck, Germany
Komorowski L:: Institute for Experimental Immunology, Euroimmun AG, D-23560 Lübeck, Germany
Kümpfel T:: Institute of Clinical Neuroimmunology, Biomedical Center and Hospital of the Ludwig-Maximilians-Universität München, D-82152 Martinsried, Germany
Hohlfeld R:: Institute of Clinical Neuroimmunology, Biomedical Center and Hospital of the Ludwig-Maximilians-Universität München, D-82152 Martinsried, Germany

Munich Cluster for Systems Neurology (SyNergy), Ludwig-Maximilians-Universität München, D-81377 München, Germany
Meuth SG:: Department of Neurology, Heinrich-Heine-University of Düsseldorf, D-40225 Düsseldorf, Germany
Casanova B:: Neuroimmunology Unit, Hospital Universitari i Politècnic la Fe, 46026 Valencia, Spain
Melzer N:: Department of Neurology, Institute of Translational Neurology, University of Münster, D-48149 Münster, Germany
Beltrán E:: Institute of Clinical Neuroimmunology, Biomedical Center and Hospital of the Ludwig-Maximilians-Universität München, D-82152 Martinsried, Germany
Dornmair K:: Institute of Clinical Neuroimmunology, Biomedical Center and Hospital of the Ludwig-Maximilians-Universität München, D-82152 Martinsried, Germany

Munich Cluster for Systems Neurology (SyNergy), Ludwig-Maximilians-Universität München, D-81377 München, Germany

Keywords

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

Campos de estudio

Proyectos asociados

PROYECTO CAIBER

CAI08/01/0061 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2009

RED DE BIOBANCOS (BIOBANCOS)

RD09/0076/00021 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2010

PATRONES DE RM CEREBRAL Y MEDULAR EN RELACION CON LA PRESENCIA DE AUTOANTIGENOS NEURONALES RECONOCIDOS POR INMUNOGLOBULINAS M PRESENTES EN EL LIQUIDO CEFALORRAQUIDEO DE PACIENTES DE ESCLEROSIS MULTIPLE.

Investigador Principal: ISABEL BOSCÁ BLASCO

MERCK SERONO DR. CASANOVA . ALMIRALL S.A; FUNDACIÓN BIOGEN IDEC; MERCK S.L.U; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2010