Children with Narcolepsy type 1 have increased T-cell responses to orexins.

Andrew C Cogswell,Thomas E Scammell,Zachary S Orban,Igor J Koralnik,Dominique Tucker,Kiran Maski

doi:10.1002/acn3.50908

Abstract

Narcolepsy type 1 (NT1) is caused by severe loss of the orexin neurons, and is highly associated with HLA DQB1*06:02. Using intracellular cytokine staining, we observed a higher frequency of IFN‐γ‐ and TNF‐α‐producing CD4+ and CD8+ T‐cells in response to orexins in 27 children with NT1 compared to 15 healthy control children. Conversely, no such difference was observed between 14 NT1 and 16 HC adults. In addition, priming with flu peptides amplified the T‐cell response to orexins in children with NT1. Our data suggests that NT1 may be caused by an autoimmune T‐cell response to orexins, possibly triggered by flu antigens.

Highlights

Narcolepsy type 1 (NT1) is a neurological disorder characterized by chronic daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis
We characterized the cellular immune response to orexins mediated by CD4+ and CD8+ T-cells in peripheral blood of NT1 subjects and determined whether it can be amplified by priming these cells with flu antigen
All NT1 subjects were positive for the HLA DQB1*06:02 allele

Summary

Introduction

Narcolepsy type 1 (NT1) is a neurological disorder characterized by chronic daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis. We characterized the cellular immune response to orexins mediated by CD4+ and CD8+ T-cells in peripheral blood of NT1 subjects and determined whether it can be amplified by priming these cells with flu antigen. The orexin peptide library was subdivided and pulsed into four equal pools at a final concentration of 2 ug/uL, each spanning an equivalent amount of the protein. Due to the limited number of PBMCs obtained from pediatric subjects, cells were pulsed with the entire orexin peptide library together at a final concentration of 2 ug/ uL. PBMCs from a subset of 10 pediatric NT1 and 7 HC subjects were initially pulsed with either the orexin (O) or H1 flu (F) peptide libraries and cultured as previously described.

Results

Discussion

Conflicts of interests