Research ArticleENCEPHALITIS

Autoimmune receptor encephalitis in mice induced by active immunization with conformationally stabilized holoreceptors

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Science Translational Medicine  10 Jul 2019:
Vol. 11, Issue 500, eaaw0044
DOI: 10.1126/scitranslmed.aaw0044

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  • RE: Active immunization, autoimmunity and encephalitis: The missing links
    • Hannelore Ehrenreich, Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen
    • Other Contributors:
      • Hong Pan, Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen
      • Michael Hollmann2, Department of Biochemistry I – Receptor Biochemistry, Ruhr University, Bochum

    We read with interest the article by Jones et al ‘Autoimmune receptor encephalitis in mice induced by active immunization with conformationally stabilized holoreceptors’ (1). The authors immunized mice with conformationally stabilized tetrameric NMDA receptors (GluN1/GluN2B or GluN1/GluN2A), liposome-embedded, and induced fulminant encephalitis. Highly variable behavioral changes included hyperactivity, immobility, circling, seizures, hunched back/lethargy and increased mortality - all non-specific features of any severe encephalitis. Besides neuroinflammation/immune cell infiltration, presence of NMDAR-AB was confirmed by immunohistochemistry/Western blot.

    While we agree that this encephalitis model, using an elegant immunization strategy, may be of value to study fulminant brain inflammation, we are not yet convinced that it ‘recapitulates the core features of human anti-NMDA receptor encephalitis’. To substantiate such claim, more adequate controls and additional information are required: (i) Instead of injecting liposomes or saline, other liposome-embedded holoreceptors would be proper controls. With the expertise of Eric Gouaux, control mice could have been immunized with GABAA-proteoliposomes (2). It cannot be excluded that a similar non-specific clinical picture would arise. (ii) Another control protein of similar size (preferably peripherally expressed or even non-mammalian) would be required to try and causally link any encephalitis with brain-expressed pro...

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    Competing Interests: None declared.