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

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

doi:10.1016/j.sleep.2017.11.1150

Cited by 17 publications

(5 citation statements)

References 39 publications

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“…When comparing patients with NT1 to age-matched siblings, we did not find any differences between blood mononuclear cell levels of CD4 and CD8 T lymphocytes, B lymphocytes, NK or NKT cells. This is consistent with previous reports [52,53].…”

Section: Discussionsupporting

confidence: 94%

High nocturnal sleep fragmentation is associated with low T lymphocyte P2Y11 protein levels in narcolepsy type 1

Viste

Viken

Lie

et al. 2021

Sleep

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Study objectives Narcolepsy type 1 (NT1) is associated with hypocretin neuron loss. However, there are still unexplained phenotypic NT1 features. We investigated the associations between clinical and sleep phenotypic characteristics, the NT1-associated P2RY11 polymorphism rs2305795, and P2Y11 protein levels in T lymphocytes in patients with NT1, their first-degree relatives and unrelated controls. Methods The P2RY11 SNP was genotyped in 100 patients (90/100 H1N1-(Pandemrix TM)-vaccinated), 119 related and 123 non-related controls. CD4 and CD8 T lymphocyte P2Y11 protein levels were quantified using flow cytometry in 167 patients and relatives. Symptoms and sleep recording parameters were also collected. Results We found an association between NT1 and the rs2305795 A allele (OR= 2, 95% CI (1.3, 3.0), p= 0.001). T lymphocyte P2Y11 protein levels were significantly lower in patients and relatives homozygous for the rs2305795 risk A allele (CD4: p= 0.012; CD8: p= 0.007). The nocturnal sleep fragmentation index was significantly negatively correlated with patients’ P2Y11 protein levels (CD4: p= 0.004; CD8: p= 0.006). Mean MSLT sleep latency, REM-sleep latency, and core clinical symptoms were not associated with P2Y11 protein levels. Conclusions We confirmed that the P2RY11 polymorphism rs2305795 is associated with NT1 also in a mainly H1N1-(Pandemrix™)-vaccinated cohort. We demonstrated that homozygosity for the A risk allele is associated with lower P2Y11 protein levels. A high level of nocturnal sleep fragmentation was associated with low P2Y11 levels in patients. This suggests that P2Y11 has a previously unknown function in sleep-wake stabilisation that affects the severity of NT1.

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Section: Discussionsupporting

confidence: 94%

High nocturnal sleep fragmentation is associated with low T lymphocyte P2Y11 protein levels in narcolepsy type 1

Viste

Viken

Lie

et al. 2021

Sleep

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“…Schinkelshoek, et al Journal of Neuroimmunology 332 (2019) 167-175 Another limitation in our study is that we are performing our experiments in blood, while the actual destruction of Hcrt-producing neurons is taking place at the other side of the blood-brain barrier. It was recently described that T cell composition in cerebrospinal fluid differed between narcolepsy type 1 patients and healthy controls (Moresco et al, 2018). Repeating our experiments in cerebrospinal fluid would therefore be a better environment to test for cross-reactive T cells.…”

Section: Discussionmentioning

confidence: 81%

H1N1 hemagglutinin-specific HLA-DQ6-restricted CD4+ T cells can be readily detected in narcolepsy type 1 patients and healthy controls

Schinkelshoek

Fronczek

Kooy-Winkelaar

et al. 2019

Journal of Neuroimmunology

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Following the 2009 H1N1 influenza pandemic, an increased risk of narcolepsy type 1 was observed. Homology between an H1N1 hemagglutinin and two hypocretin sequences has been reported. T cell reactivity to these peptides was assessed in 81 narcolepsy type 1 patients and 19 HLA-DQ6-matched healthy controls. HLA-DQ6-restricted H1N1 hemagglutinin-specific T cell responses were detected in 28.4% of patients and 15.8% of controls. Despite structural homology between HLA-DQ6-hypocretin and-H1N1 peptide complexes, T cell cross-reactivity was not detected. These results indicate that it is unlikely that cross-reactivity between H1N1 hemagglutinin and hypocretin peptides presented by HLA-DQ6 is involved in the development of narcolepsy.

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“…In our study, this subset was similar in the two groups, and high percentage and absolute count of Tregs, while we only found an increase in Tr1 in ROHHAD(NET), and no difference in Treg; cytokine production by CD4 + and CD8 + T cells—including IL-8 levels—was not modified in NT1 patients in this study. Other authors [ 40 ] found no significant difference in PB CD4 + or CD8 + between 14 NT1 patients and healthy individuals. Even though NT1 has some clinical and biochemical features in common with ROHHAD(NET), namely the hypothalamic involvement, the presence of obesity, central precocious puberty, altered sleep pattern, and reduced CSF hypocretin levels [ 41-44 ], PB lymphocyte subsets do not show the same alterations in these 2 diseases.…”

Section: Discussionmentioning

confidence: 88%

Blood Lymphocyte Subsets and Proinflammatory Cytokine Profile in ROHHAD(NET) and non-ROHHAD(NET) Obese Individuals

Fava

Morandi

Prigione

et al. 2023

Journal of the Endocrine Society

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Context Rapid-onset obesity with central hypoventilation, hypothalamic dysfunction, and autonomic dysregulation with neural crest tumors (ROHHAD-NET) syndrome pathophysiology remains elusive. Acquired neuroimmunological dysfunction has been proposed as a possible pathogenetic pathway. Objective The aim of our study was to characterize lymphocyte subpopulations subsets in peripheral blood (PB) and to evaluate a panel of proinflammatory cytokines/chemokines in ROHHAD(NET) patients vs controls. Methods We included 11 ROHHAD(NET) patients, 7 ROHHAD and 4 ROHHAD-NET, selected by clinical criteria. Controls were 11 simple obese children, matched for age and sex. Flow cytometric analysis and enzyme-linked immunosorbent assay were performed on PB and serum samples of the 2 groups. Results Analysis revealed that T lymphocytes are significantly increased in ROHHAD(NET) patients (P = .04) with a prevalence of CD4-T cells (P = .03) and a lower number of activated CD8-T cells (P = .02). With regard to regulatory subset, patients displayed increased regulatory B cells (P = .05) and type-1 regulatory T cells (P = .03). With regard to CD8-T cells, a lower number of T effector memory was observed (P = .02). In contrast, among CD4-T cells, we found a higher number of T naive (P = .04) and T effector (P = .0008). Interleukin-8 (IL-8) levels and monocyte chemotactic protein-1 were increased in patients vs controls (P = .008 and P = .01, respectively). Furthermore, IL-8 levels were higher in the subgroup with neural tumor (P = .0058) (ROHHAD-NET) than in patients without neural tumor (ROHHAD). Soluble HLA-G was significantly lower in patients vs controls (P = .03). Conclusion Our findings contribute to support the hypothesis of immune dysregulation, which may underlie this complex, often fatal disease. Because ROHHAD(NET) syndrome is an ultra-rare disease, multicentric studies are needed to improve the effect of our data in the management of this condition.

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

Cited by 17 publications

References 39 publications

High nocturnal sleep fragmentation is associated with low T lymphocyte P2Y11 protein levels in narcolepsy type 1

High nocturnal sleep fragmentation is associated with low T lymphocyte P2Y11 protein levels in narcolepsy type 1

H1N1 hemagglutinin-specific HLA-DQ6-restricted CD4+ T cells can be readily detected in narcolepsy type 1 patients and healthy controls

Blood Lymphocyte Subsets and Proinflammatory Cytokine Profile in ROHHAD(NET) and non-ROHHAD(NET) Obese Individuals

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