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

Findings suggest narcolepsy type 1 to be a T-cell mediated autoimmune disease targeting hypocretin-producing Neurons.

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.

In the study by Latorre et al., 2018 a sensitive cellular screens have been used and hypocretin-specific CD4+ T cells in all 19 patients tested have been detected; 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.

In another study (Pedersen et al., 2019), 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 suggest that a certain level of CD8+ T-cell reactivity combined with HLA-DQB1*06:02 expression is important for NT1 development and solidify the autoimmune aetiology of narcolepsy, providing a basis for rapid diagnosis and treatment of this disease.

Key Points

  • T cells in patients with narcolepsy target self-antigens of hypocretin neurons
  • Hypocretin-specific CD4+ T cells detected in all patients tested (NT1 and NT2)
  • T cells specific for tribbles homologue 2—another self-antigen of hypocretin neurons—were also found
  • Autoreactive CD8+ cells clonotypes were serially detected in the blood of the same—and even of different—patients, but not in healthy control individuals

References

<link www.nature.com/articles/s41586-018-0540-1>T cells in patients with narcolepsy target self-antigens of hypocretin neurons</link>

Daniela Latorre, Ulf Kallweit, Eric Armentani, Mathilde Foglierini, Federico Mele, Antonino Cassotta,

Sandra Jovic, David Jarrossay, Johannes Mathis, Francesco Zellini6, Burkhard Becher, Antonio Lanzavecchia, Ramin Khatami8, Mauro Manconi, Mehdi Tafti, Claudio L. Bassetti & Federica Sallusto

 

<link www.nature.com/articles/s41467-019-08774-1&gt;CD8+ T cells from patients with narcolepsy and healthy controls recognize hypocretin neuron-specific antigens</link>

Natasja Wulff Pedersen, Anja Holm, Nikolaj Pagh Kristensen, Anne-Mette Bjerregaard ,

Amalie Kai Bentzen, Andrea Marion Marquard, Tripti Tamhane1, Kristoffer Sølvsten Burgdorf, Henrik Ullum,

Poul Jennum, Stine Knudsen, Sine Reker Hadrup  & Birgitte Rahbek Kornum

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