Reviewing the Clinical Implications of Treating Narcolepsy as an Autoimmune Disorder

Giannoccaro, Maria Pia; Liguori, Rocco; Plazzi, Giuseppe; Pizza, Fabio

doi:10.2147/nss.s275931

Cited by 11 publications

(5 citation statements)

References 113 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Such work is essential for bridging the gaps in the current understanding of narcolepsy in the scientific community [ 1 ]. Previous studies have predicted that narcolepsy is associated with autoimmunity after investigating the ‘criteria of autoimmune disease’ in narcolepsy cases [ 7 , 34 , 35 , 36 ]. The relationship between human leukocyte antigen (HLA) and NT1 was significantly discussed in a study conducted by Giannoccaro et al [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have predicted that narcolepsy is associated with autoimmunity after investigating the ‘criteria of autoimmune disease’ in narcolepsy cases [ 7 , 34 , 35 , 36 ]. The relationship between human leukocyte antigen (HLA) and NT1 was significantly discussed in a study conducted by Giannoccaro et al [ 36 ]. Thus, we investigated the presence of HLA in the patients’ samples selected for this study.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

LC-MS/MS-Based Proteomics Approach for the Identification of Candidate Serum Biomarkers in Patients with Narcolepsy Type 1

et al. 2023

Self Cite

View full text Add to dashboard Cite

Narcolepsy type 1 (NT1) is the most common type of narcolepsy known to be caused by the loss of specific neurons responsible for producing peptide neurotransmitters (orexins/hypocretins), resulting in a sleep-wake cycle disorder. It is characterized by its association with cataplexy and abnormalities in rapid eye movement. To date, no cure has been established for this life-threatening condition. Misdiagnosis of NT1 is also quite common, although it is not exceedingly rare. Therefore, successfully identifying candidate serum biomarkers for NT1 would be a head start for accurate diagnosis and development of therapeutics for this disorder. This study aims to identify such potential serum biomarkers. A depletion protocol was employed for 27 human serum samples (16 NT1 and 11 healthy controls), followed by applying LC-MS/MS bottom-up proteomics analysis, then LC-PRM-MS for validation. The comparison of the proteome profiles of the low-abundant proteins in the samples was then investigated based on age, sex, sample groups, and the presence of the Human Leukocyte Antigen (HLA) DQB1*0602 allele. The results were tracked to gene expression studies as well as system biology to identify key proteins and understand their relationship in the pathogenesis of NT1. Our results revealed 36 proteins significantly and differentially expressed. Among the impaired pathways and bioprocesses, the complement activation pathway is impaired by six of the differentially expressed proteins (DEPs). They are coded by the genes C2, CFB, C5, C1R, C1S, and MASP1, while 11 DEPs are involved in Acute Phase Response Signaling (APRS), which are coded by the genes FN1, AMBP, APOH, CFB, CP, ITIH2, C5, C2, F2, C1, and ITIH4. The combined AUCs of the downregulated and upregulated DEPs are 0.95 and 0.76, respectively. Overall, this study reveals potential serum-protein biomarkers of NT1 and explains the possible correlation between the biomarkers and pathophysiological effects, as well as important biochemical pathways involved in NT1.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

LC-MS/MS-Based Proteomics Approach for the Identification of Candidate Serum Biomarkers in Patients with Narcolepsy Type 1

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…To understand NT1, a disease that has not yet been fully investigated, it is crucial to discover the glycosylation sites in glycoproteins in disease samples and therefore increase prediction for its diagnosis [4]. Due to a meaningful relationship between human leukocyte antigen (HLA) and NT1 [49], patient samples with existing HLA typing were chosen for this study. The focus of the present study was to profile the N-glycopeptides derived and enriched from low-abundance serum glycoproteins, because the wide dynamic range of high-abundance serum proteins would cover the presence of the low-abundance proteins that play a prominent role in the development of numerous diseases [50][51][52] and, more specifically, for NT1 patients in this study.…”

Section: Discussionmentioning

confidence: 99%

LC-MS/MS Quantitation of HILIC-Enriched N-glycopeptides Derived from Low-Abundance Serum Glycoproteins in Patients with Narcolepsy Type 1

Atashi,

Reyes,

Sandilya

et al. 2023

Biomolecules

Self Cite

View full text Add to dashboard Cite

Glycoproteomic analysis is always challenging because of low abundance and complex site-specific heterogeneity. Glycoproteins are involved in various biological processes such as cell signaling, adhesion, and cell–cell communication and may serve as potential biomarkers when analyzing different diseases. Here, we investigate glycoproteins in narcolepsy type 1 (NT1) disease, a form of narcolepsy characterized by cataplexy—the sudden onset of muscle paralysis that is typically triggered by intense emotions. In this study, 27 human blood serum samples were analyzed, 16 from NT1 patients and 11 from healthy individuals serving as controls. We quantified hydrophilic interaction liquid chromatography (HILIC)-enriched glycopeptides from low-abundance serum samples of controls and NT1 patients via LC-MS/MS. Twenty-eight unique N-glycopeptides showed significant changes between the two studied groups. The sialylated N-glycopeptide structures LPTQNITFQTESSVAEQEAEFQSPK HexNAc6, Hex3, Neu5Ac2 (derived from the ITIH4 protein) and the structure IVLDPSGSMNIYLVLDGSDSIGASNFTGAK HexNAc5, Hex4, Fuc1 (derived from the CFB protein), with p values of 0.008 and 0.01, respectively, were elevated in NT1 samples compared with controls. In addition, the N-glycopeptide protein sources Ceruloplasmin, Complement factor B, and ITH4 were observed to play an important role in the complement activation and acute-phase response signaling pathways. This may explain the possible association between the biomarkers and pathophysiological effects.

show abstract

“…In addition, interactions between sleep and innate immunity are considered as bidirectional, as immune activation alters sleep, and sleep disturbance in turn could affect immune functions 48 . Until now, immunotherapies in narcoleptic patients have reported poor beneficial results 49 . However, immunotherapy intervention in targeted patients such as RWG children could give the opportunity to stop the autoimmune process and thus reduce the hypocretin neuronal loss at the early stages of the disease.…”

Section: Discussionmentioning

confidence: 99%

Characterization of rapid weight gain phenotype in children with narcolepsy

et al. 2022

View full text Add to dashboard Cite

Objectives To characterize the rapid weight gain (RWG) phenotype associated with the onset of childhood narcolepsy and to determine whether it could constitute a marker of severity of the disease. Methods RWG was defined using the BMI z‐score slope reported to one year (>0.67 SD) from symptom onset to disease diagnosis. We compared the clinical, metabolic, and sleep characteristics between patients with or without RWG at diagnosis. Pharmacological management, anthropometric, and clinical progression were also evaluated during the follow‐up. Results A total of 84 de novo narcoleptic pediatric patients were included; their median age at diagnosis was 12.0 years; 59.5% boys, 90.5% cataplexy, and 98.7% HLA‐DQB1*06:02, 57% had RWG profile. RWG patients were younger at diagnosis than non‐RWG patients, despite a shorter diagnostic delay. They had a higher BMI z‐score and a higher prevalence of obesity at diagnosis, but not at symptom onset, and higher adapted Epworth Sleepiness Scale and Insomnia Severity Index scores than non‐RWG patients. No differences on nocturnal polysomnography and multiple sleep latency tests were found between groups at disease diagnosis. After a median follow‐up of 5 years, RWG patients still had a higher BMI z‐score and a higher prevalence of obesity despite benefiting from the same therapeutic management and displaying improvement in sleepiness and school difficulties. Conclusions Narcoleptic RWG patients were younger, sleepier, and the prevalence of obesity was higher at diagnosis despite a shorter diagnostic delay than that of non‐RWG patients. These patients had also a higher risk of developing a long‐term obesity, despite a positive progression of their narcoleptic symptoms. RGW could then represent a maker of a more severe phenotype of childhood narcolepsy, which should inspire a prompt and more offensive management to prevent obesity and its complications.

show abstract

Reviewing the Clinical Implications of Treating Narcolepsy as an Autoimmune Disorder

Cited by 11 publications

References 113 publications

LC-MS/MS-Based Proteomics Approach for the Identification of Candidate Serum Biomarkers in Patients with Narcolepsy Type 1

LC-MS/MS-Based Proteomics Approach for the Identification of Candidate Serum Biomarkers in Patients with Narcolepsy Type 1

LC-MS/MS Quantitation of HILIC-Enriched N-glycopeptides Derived from Low-Abundance Serum Glycoproteins in Patients with Narcolepsy Type 1

Characterization of rapid weight gain phenotype in children with narcolepsy

Contact Info

Product

Resources

About