Absence of autoreactive CD4(+) T-cells targeting HLA-DQA1*01:02/DQB1*06:02 restricted hypocretin/orexin epitopes in narcolepsy type 1 when detected by EliSpot

Birgitte Rahbek Kornum; Kristoffer Sølvsten Burgdorf; Anja Holm; Henrik Ullum; Poul Jennum; Stine Knudsen

doi:10.1016/j.jneuroim.2017.05.001

Absence of autoreactive CD4(+) T-cells targeting HLA-DQA101:02/DQB106:02 restricted hypocretin/orexin epitopes in narcolepsy type 1 when detected by EliSpot

Birgitte Rahbek Kornum, Kristoffer Sølvsten Burgdorf, Anja Holm, Henrik Ullum, Poul Jennum, Stine Knudsen

Department of Clinical Medicine

10 Citations (Scopus)

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.

Original language	English
Journal	Journal of Neuroimmunology
Volume	309
Pages (from-to)	7-11
Number of pages	5
ISSN	0165-5728
DOIs	https://doi.org/10.1016/j.jneuroim.2017.05.001
Publication status	Published - 15 Aug 2017

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Absence of autoreactive CD4(+) T-cells targeting HLA-DQA1*01:02/DQB1*06:02 restricted hypocretin/orexin epitopes in narcolepsy type 1 when detected by EliSpot. / Kornum, Birgitte Rahbek ; Burgdorf, Kristoffer Sølvsten; Holm, Anja et al.

In: Journal of Neuroimmunology, Vol. 309, 15.08.2017, p. 7-11.

Research output: Contribution to journal › Journal article › Research › peer-review

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title = "Absence of autoreactive CD4(+) T-cells targeting HLA-DQA1*01:02/DQB1*06:02 restricted hypocretin/orexin epitopes in narcolepsy type 1 when 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.",

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AU - Kornum, Birgitte Rahbek

AU - Burgdorf, Kristoffer Sølvsten

AU - Holm, Anja

AU - Ullum, Henrik

AU - Jennum, Poul

AU - Knudsen, Stine

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N2 - 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.

AB - 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.

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