title: CD8(+) T-cell pathogenicity in Rasmussen encephalitis elucidated by large-scale T-cell receptor sequencing.
abstract: Rasmussen encephalitis (RE) is a rare paediatric epilepsy with uni-hemispheric inflammation and progressive neurological deficits. To elucidate RE immunopathology, we applied T-cell receptor (TCR) sequencing to blood (n=23), cerebrospinal fluid (n=2) and brain biopsies (n=5) of RE patients, and paediatric controls. RE patients present with peripheral CD8(+) T-cell expansion and its strength correlates with disease severity. In addition, RE is the only paediatric epilepsy with prominent T-cell expansions in the CNS. Consistently, common clones are shared between RE patients, who also share MHC-I alleles. Public RE clones share Vβ genes and length of the CDR3. Rituximab/natalizumab/basiliximab treatment does not change TCR diversity, stem cell transplantation replaces the TCR repertoire with minimal overlap between donor and recipient, as observed in individual cases. Our study supports the hypothesis of an antigen-specific attack of peripherally expanded CD8(+) lymphocytes against CNS structures in RE, which might be ameliorated by restricting access to the CNS.
authors.affiliation: Department of Neurology, University of Münster, 48149 Münster, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Schneider-Hohendorf
authors.affiliation: Department of Neurology, University of Münster, 48149 Münster, Germany.
authors.forename: Hema
authors.initials: H
authors.lastname: Mohan
authors.affiliation: Epilepsy Center Bethel, Krankenhaus Mara, 33617 Bielefeld, Germany.
authors.forename: Christian G
authors.initials: CG
authors.lastname: Bien
authors.affiliation: Department of Neurology, University of Münster, 48149 Münster, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Breuer
authors.affiliation: Institute of Neuropathology, University Hospital Bonn, 53105 Bonn, Germany.
authors.forename: Albert
authors.initials: A
authors.lastname: Becker
authors.affiliation: Institute of Biostatistics and Clinical Research, University of Münster, 48149 Münster, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Görlich
authors.affiliation: Department of Neuropathology, University of Münster, 48149 Münster, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Kuhlmann
authors.affiliation: Department of Epileptology, University of Bonn, 53127 Bonn, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Widman
authors.affiliation: Department of Neurology, University of Münster, 48149 Münster, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Herich
authors.affiliation: Children's Hospital of the University Medical Center, University of Münster, 48149 Münster, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Elpers
authors.affiliation: Department of Neurology, University of Münster, 48149 Münster, Germany.
authors.forename: Nico
authors.initials: N
authors.lastname: Melzer
authors.affiliation: Institute for Clinical Neuroimmunology, Ludwig-Maximilians-University Munich, 80539 Munich, Germany.|Biomedical Center, Ludwig-Maximilians-University Munich, 80539 Munich, Germany.|Munich Cluster for Systems Neurology (SyNergy), Ludwig-Maximilians-University Munich, 80539 Munich, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Dornmair
authors.affiliation: Children's Hospital of the University Medical Center, University of Münster, 48149 Münster, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Kurlemann
authors.affiliation: Department of Neurology, University of Münster, 48149 Münster, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Wiendl
authors.affiliation: Department of Neurology, University of Münster, 48149 Münster, Germany.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Schwab
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000077552:Basiliximab; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002490:Central Nervous System / Q000473:pathology*; D004660:Encephalitis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008969:Molecular Sequence Data; D000069442:Natalizumab / Q000627:therapeutic use; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D000069283:Rituximab / Q000627:therapeutic use; D020539:Sequence Analysis, Protein
chemical_list: D000911:Antibodies, Monoclonal; D000069442:Natalizumab; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D000069283:Rituximab; D000077552:Basiliximab