CD8+ T-cell pathogenicity in Rasmussen encephalitis elucidated by large-scale T-cell receptor sequencing

Tilman Schneider-Hohendorf, Hema Mohan, Christian G. Bien, Johanna Breuer, Albert Becker, Dennis Görlich, Tanja Kuhlmann, Guido Widman, Sebastian Herich, Christiane Elpers, Nico Melzer, Klaus Dornmair, Gerhard Kurlemann, Heinz Wiendl () and Nicholas Schwab ()
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Tilman Schneider-Hohendorf: University of Münster
Hema Mohan: University of Münster
Christian G. Bien: Epilepsy Center Bethel, Krankenhaus Mara
Johanna Breuer: University of Münster
Albert Becker: Institute of Neuropathology, University Hospital Bonn
Dennis Görlich: Institute of Biostatistics and Clinical Research, University of Münster
Tanja Kuhlmann: University of Münster
Guido Widman: University of Bonn
Sebastian Herich: University of Münster
Christiane Elpers: Children’s Hospital of the University Medical Center, University of Münster
Nico Melzer: University of Münster
Klaus Dornmair: Institute for Clinical Neuroimmunology, Ludwig-Maximilians-University Munich
Gerhard Kurlemann: Children’s Hospital of the University Medical Center, University of Münster
Heinz Wiendl: University of Münster
Nicholas Schwab: University of Münster

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms11153

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