CD4+ T-Cell Reactivity to Orexin/Hypocretin in Patients With Narcolepsy Type 1.

Abstract

Introduction:

Narcolepsy type 1 is accompanied by a selective loss of orexin/hypocretin (hcrt) neurons in the lateral hypothalamus caused by yet unknown mechanisms. Epidemiologic and genetic associations strongly suggest an immune-mediated pathogenesis of the disease.

Methods:

We compared specific T-cell reactivity to orexin/hcrt peptides in peripheral blood mononuclear cells of narcolepsy type 1 patients to healthy controls by a carboxyfluorescein succinimidyl ester proliferation assay. Orexin/hcrt-specific T-cell reactivity was also determined by cytokine (interferon gamma and granulocyte-macrophage colony-stimulating factor) analysis. Individuals were considered as responders if the cell division index of CD3+CD4+ T cells and both stimulation indices of cytokine secretion exceeded the cutoff 3. Additionally, T-cell reactivity to orexin/hcrt had to be confirmed by showing reactivity to single peptides present in different peptide pools.

Results:

Using these criteria, 3/15 patients (20%) and 0/13 controls (0%) showed orexin/hcrt-specific CD4+ T-cell proliferation (p = .2262). The heterogeneous reactivity pattern did not allow the identification of a preferential target epitope.

Conclusions:

A significant role of orexin/hcrt-specific T cells in narcolepsy type 1 patients could not be confirmed in this study. Further studies are needed to assess the exact role of CD4+ T cells and possible target antigens in narcolepsy type 1 patients.

• Authors: Melanie Ramberger, Birgit Högl, Ambra Stefani, Thomas Mitterling, Markus Reindl, Andreas Lutterotti
• Journal: Sleep (Sleep) Vol. 40 Issue 3 (Mar 01 2017) ISSN: 1550-9109 [Electronic] United States
• PMID: 28364420 (Publication Type: Journal Article)
• Copyright: © Sleep Research Society 2016. Published by Oxford University Press [on behalf of the Sleep Research Society].

Chemical References

• Intracellular Signaling Peptides and Proteins
• Orexins

Topics

• Adolescent
• Adult
• Aged
• Amino Acid Sequence
• CD4-Positive T-Lymphocytes (drug effects, immunology, metabolism)
• Cells, Cultured
• Child
• Female
• Humans
• Intracellular Signaling Peptides and Proteins (genetics, pharmacology)
• Leukocytes, Mononuclear (drug effects, immunology, metabolism)
• Male
• Middle Aged
• Narcolepsy (blood, immunology)
• Neurons (drug effects, immunology, metabolism)
• Orexins (genetics, pharmacology)
• Young Adult