Highlights
- •Narcolepsy type 1 is a suspected autoimmune sleep disorder associated with HLA-DQB1*06:02
- •The hypocretin/orexin producing neurons are selectively destroyed.
- •Genetic association points the involvement of CD4+ T-cells.
- •Five epitopes from the hypocretin precursor are predicted to bind MHC DQA1*01:02/DQB1*06:02.
- •CD4+ T-cells from narcolepsy type 1 patients targeting these epitopes are not detected by EliSpot.
Abstract
Narcolepsy type 1, a neurological sleep disorder strongly associated with Human Leukocyte
Antigen (HLA-)DQB1*06:02, is caused by the loss of hypothalamic neurons producing
the wake-promoting neuropeptide hypocretin (hcrt, also known as orexin). This loss
is believed to be caused by an autoimmune reaction. To test whether hcrt itself could
be a possible target in the autoimmune attack, CD4+ T-cell reactivity towards six different 15-mer peptides from prepro-hypocretin with
high predicted affinity to the DQA1*01:02/DQB1*06:02 MHC class II dimer was tested
using EliSpot in a cohort of 22 narcolepsy patients with low CSF hcrt levels, and
23 DQB1*06:02 positive healthy controls. Our ELISpot assay had a detection limit of
1:10,000 cells.
We present data showing that autoreactive CD4+ T-cells targeting epitopes from the hcrt precursor in the context of MHC-DQA1*01:02/DQB1*06:02
are either not present or present in a frequency is <1:10,000 among peripheral CD4+ T-cells from narcolepsy type 1 patients.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: May 04, 2017
Accepted:
May 1,
2017
Received in revised form:
April 27,
2017
Received:
January 10,
2017
Identification
Copyright
© 2017 Elsevier B.V. All rights reserved.
