T cells in patients with narcolepsy target self-antigens of hypocretin neurons

Daniela Latorre, Ulf Kallweit, Eric Armentani, Mathilde Foglierini, Federico Mele, Antonino Cassotta, Sandra Jovic, David Jarrossay, Johannes Mathis, Francesco Zellini, Burkhard Becher, Antonio Lanzavecchia, Ramin Khatami, Mauro Manconi, Mehdi Tafti, Claudio L. Bassetti () and Federica Sallusto ()
Additional contact information
Daniela Latorre: Università della Svizzera italiana
Ulf Kallweit: University Hospital
Eric Armentani: Università della Svizzera italiana
Mathilde Foglierini: Università della Svizzera italiana
Federico Mele: Università della Svizzera italiana
Antonino Cassotta: Università della Svizzera italiana
Sandra Jovic: Università della Svizzera italiana
David Jarrossay: Università della Svizzera italiana
Johannes Mathis: University Hospital
Francesco Zellini: Neurocenter of Southern Switzerland
Burkhard Becher: University of Zurich
Antonio Lanzavecchia: Università della Svizzera italiana
Ramin Khatami: Clinic Barmelweid
Mauro Manconi: University Hospital
Mehdi Tafti: Faculty of Biology and Medicine, University of Lausanne
Claudio L. Bassetti: University Hospital
Federica Sallusto: Università della Svizzera italiana

Nature, 2018, vol. 562, issue 7725, 63-68

Abstract: Abstract Narcolepsy is a chronic sleep disorder caused by the loss of neurons that produce hypocretin. The close association with HLA-DQB1*06:02, evidence for immune dysregulation and increased incidence upon influenza vaccination together suggest that this disorder has an autoimmune origin. However, there is little evidence of autoreactive lymphocytes in patients with narcolepsy. Here we used sensitive cellular screens and detected hypocretin-specific CD4+ T cells in all 19 patients that we tested; T cells specific for tribbles homologue 2—another self-antigen of hypocretin neurons—were found in 8 out of 13 patients. Autoreactive CD4+ T cells were polyclonal, targeted multiple epitopes, were restricted primarily by HLA-DR and did not cross-react with influenza antigens. Hypocretin-specific CD8+ T cells were also detected in the blood and cerebrospinal fluid of several patients with narcolepsy. Autoreactive clonotypes were serially detected in the blood of the same—and even of different—patients, but not in healthy control individuals. These findings solidify the autoimmune aetiology of narcolepsy and provide a basis for rapid diagnosis and treatment of this disease.

Keywords: Hypocretin (HCRT); HCRT Neurons; Tribbles Homologue 2 (TRIB2); Clonotypes; Narcolepsy Type (search for similar items in EconPapers)
Date: 2018
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DOI: 10.1038/s41586-018-0540-1

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