Flow cytometry analysis of T-cell subsets in cerebrospinal fluid of narcolepsy type 1 patients with long-lasting disease

Monica Moresco; Mariangela Lecciso; Darina Ocadlikova; Marco Filardi; Silvia Melzi; Birgitte Rahbek Kornum; Elena Antelmi; Fabio Pizza; Emmanuel Mignot; Antonio Curti; Giuseppe Plazzi

doi:10.1016/j.sleep.2017.11.1150

Flow cytometry analysis of T-cell subsets in cerebrospinal fluid of narcolepsy type 1 patients with long-lasting disease

Monica Moresco, Mariangela Lecciso, Darina Ocadlikova, Marco Filardi, Silvia Melzi, Birgitte Rahbek Kornum, Elena Antelmi, Fabio Pizza, Emmanuel Mignot, Antonio Curti, Giuseppe Plazzi

6 Citations (Scopus)

Abstract

BACKGROUND: Type 1 narcolepsy (NT1) is a central hypersomnia linked to the destruction of hypocretin-producing neurons. A great body of genetic and epidemiological data points to likely autoimmune disease aetiology. Recent reports have characterized peripheral blood T-cell subsets in NT1, whereas data regarding the cerebrospinal fluid (CSF) immune cell composition are lacking. The current study aimed to characterize the T-cell and natural killer (NK) cell subsets in NT1 patients with long disease course.

METHODS: Immune cell subsets from CSF and peripheral blood mononuclear cell (PBMC) samples were analysed by flow cytometry in two age-balanced and sex-balanced groups of 14 NT1 patients versus 14 healthy controls. The frequency of CSF cell groups was compared with PBMCs. Non-parametric tests were used for statistical analyses.

RESULTS: The NT1 patients did not show significant differences of CSF immune cell subsets compared to controls, despite a trend towards higher CD4+ terminally differentiated effector memory T cells. T cells preferentially displayed a memory phenotype in the CSF compared to PBMCs. Furthermore, a reduced frequency of CD4+ terminally differentiated effector memory T cells and an increased frequency of NK CD56bright cells was observed in PBMCs from patients compared to controls. Finally, the ratio between CSF and peripheral CD4+ terminally differentiated effector memory T cells was two-fold increased in NT1 patients versus controls.

CONCLUSIONS: Significant differences in PBMCs and in CSF/PBMC ratios of immune cell profile were found in NT1 patients compared to healthy controls. These differences might have arisen from the different HLA status, or be primary or secondary to hypocretin deficiency. Further functional studies in patients close to disease onset are required to understand NT1 pathophysiology.

Original language	English
Journal	Sleep Medicine
Volume	44
Pages (from-to)	53-60
Number of pages	8
ISSN	1389-9457
DOIs	https://doi.org/10.1016/j.sleep.2017.11.1150
Publication status	Published - Apr 2018
Externally published	Yes

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10.1016/j.sleep.2017.11.1150

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@article{0bda364d00a44fd2a3f74d9e10849812,

title = "Flow cytometry analysis of T-cell subsets in cerebrospinal fluid of narcolepsy type 1 patients with long-lasting disease",

abstract = "BACKGROUND: Type 1 narcolepsy (NT1) is a central hypersomnia linked to the destruction of hypocretin-producing neurons. A great body of genetic and epidemiological data points to likely autoimmune disease aetiology. Recent reports have characterized peripheral blood T-cell subsets in NT1, whereas data regarding the cerebrospinal fluid (CSF) immune cell composition are lacking. The current study aimed to characterize the T-cell and natural killer (NK) cell subsets in NT1 patients with long disease course.METHODS: Immune cell subsets from CSF and peripheral blood mononuclear cell (PBMC) samples were analysed by flow cytometry in two age-balanced and sex-balanced groups of 14 NT1 patients versus 14 healthy controls. The frequency of CSF cell groups was compared with PBMCs. Non-parametric tests were used for statistical analyses.RESULTS: The NT1 patients did not show significant differences of CSF immune cell subsets compared to controls, despite a trend towards higher CD4+ terminally differentiated effector memory T cells. T cells preferentially displayed a memory phenotype in the CSF compared to PBMCs. Furthermore, a reduced frequency of CD4+ terminally differentiated effector memory T cells and an increased frequency of NK CD56bright cells was observed in PBMCs from patients compared to controls. Finally, the ratio between CSF and peripheral CD4+ terminally differentiated effector memory T cells was two-fold increased in NT1 patients versus controls.CONCLUSIONS: Significant differences in PBMCs and in CSF/PBMC ratios of immune cell profile were found in NT1 patients compared to healthy controls. These differences might have arisen from the different HLA status, or be primary or secondary to hypocretin deficiency. Further functional studies in patients close to disease onset are required to understand NT1 pathophysiology.",

author = "Monica Moresco and Mariangela Lecciso and Darina Ocadlikova and Marco Filardi and Silvia Melzi and Kornum, {Birgitte Rahbek} and Elena Antelmi and Fabio Pizza and Emmanuel Mignot and Antonio Curti and Giuseppe Plazzi",

year = "2018",

month = apr,

doi = "10.1016/j.sleep.2017.11.1150",

language = "English",

volume = "44",

pages = "53--60",

journal = "Sleep Medicine",

issn = "1389-9457",

publisher = "Elsevier",

}

TY - JOUR

T1 - Flow cytometry analysis of T-cell subsets in cerebrospinal fluid of narcolepsy type 1 patients with long-lasting disease

AU - Moresco, Monica

AU - Lecciso, Mariangela

AU - Ocadlikova, Darina

AU - Filardi, Marco

AU - Melzi, Silvia

AU - Kornum, Birgitte Rahbek

AU - Antelmi, Elena

AU - Pizza, Fabio

AU - Mignot, Emmanuel

AU - Curti, Antonio

AU - Plazzi, Giuseppe

PY - 2018/4

Y1 - 2018/4

N2 - BACKGROUND: Type 1 narcolepsy (NT1) is a central hypersomnia linked to the destruction of hypocretin-producing neurons. A great body of genetic and epidemiological data points to likely autoimmune disease aetiology. Recent reports have characterized peripheral blood T-cell subsets in NT1, whereas data regarding the cerebrospinal fluid (CSF) immune cell composition are lacking. The current study aimed to characterize the T-cell and natural killer (NK) cell subsets in NT1 patients with long disease course.METHODS: Immune cell subsets from CSF and peripheral blood mononuclear cell (PBMC) samples were analysed by flow cytometry in two age-balanced and sex-balanced groups of 14 NT1 patients versus 14 healthy controls. The frequency of CSF cell groups was compared with PBMCs. Non-parametric tests were used for statistical analyses.RESULTS: The NT1 patients did not show significant differences of CSF immune cell subsets compared to controls, despite a trend towards higher CD4+ terminally differentiated effector memory T cells. T cells preferentially displayed a memory phenotype in the CSF compared to PBMCs. Furthermore, a reduced frequency of CD4+ terminally differentiated effector memory T cells and an increased frequency of NK CD56bright cells was observed in PBMCs from patients compared to controls. Finally, the ratio between CSF and peripheral CD4+ terminally differentiated effector memory T cells was two-fold increased in NT1 patients versus controls.CONCLUSIONS: Significant differences in PBMCs and in CSF/PBMC ratios of immune cell profile were found in NT1 patients compared to healthy controls. These differences might have arisen from the different HLA status, or be primary or secondary to hypocretin deficiency. Further functional studies in patients close to disease onset are required to understand NT1 pathophysiology.

AB - BACKGROUND: Type 1 narcolepsy (NT1) is a central hypersomnia linked to the destruction of hypocretin-producing neurons. A great body of genetic and epidemiological data points to likely autoimmune disease aetiology. Recent reports have characterized peripheral blood T-cell subsets in NT1, whereas data regarding the cerebrospinal fluid (CSF) immune cell composition are lacking. The current study aimed to characterize the T-cell and natural killer (NK) cell subsets in NT1 patients with long disease course.METHODS: Immune cell subsets from CSF and peripheral blood mononuclear cell (PBMC) samples were analysed by flow cytometry in two age-balanced and sex-balanced groups of 14 NT1 patients versus 14 healthy controls. The frequency of CSF cell groups was compared with PBMCs. Non-parametric tests were used for statistical analyses.RESULTS: The NT1 patients did not show significant differences of CSF immune cell subsets compared to controls, despite a trend towards higher CD4+ terminally differentiated effector memory T cells. T cells preferentially displayed a memory phenotype in the CSF compared to PBMCs. Furthermore, a reduced frequency of CD4+ terminally differentiated effector memory T cells and an increased frequency of NK CD56bright cells was observed in PBMCs from patients compared to controls. Finally, the ratio between CSF and peripheral CD4+ terminally differentiated effector memory T cells was two-fold increased in NT1 patients versus controls.CONCLUSIONS: Significant differences in PBMCs and in CSF/PBMC ratios of immune cell profile were found in NT1 patients compared to healthy controls. These differences might have arisen from the different HLA status, or be primary or secondary to hypocretin deficiency. Further functional studies in patients close to disease onset are required to understand NT1 pathophysiology.

U2 - 10.1016/j.sleep.2017.11.1150

DO - 10.1016/j.sleep.2017.11.1150

M3 - Journal article

C2 - 29530370

SN - 1389-9457

VL - 44

SP - 53

EP - 60

JO - Sleep Medicine

JF - Sleep Medicine

ER -

Flow cytometry analysis of T-cell subsets in cerebrospinal fluid of narcolepsy type 1 patients with long-lasting disease

Abstract

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