PXD041093

PXD041093 is an original dataset announced via ProteomeXchange.

Title	Cerebrospinal fluid proteomics in recent-onset Narcolepsy type 1 reveals activation of the complement system
Description	Narcolepsy type 1 (NT1) is a rare, chronic and disabling neurological disease causing excessive daytime sleepiness and cataplexy. NT1 is characterized pathologically by an almost complete loss of neurons producing the orexin neuropeptides in the lateral hypothalamus. Genetic and environmental factors strongly suggest the involvement of the immune system in the loss of orexin neurons. The cerebrospinal fluid (CSF), secreted locally and surrounding the central nervous system (CNS), represents an accessible window into CNS pathological processes. To gain insight into the biological and molecular changes in NT1 patients, we performed a comparative proteomics analysis of the CSF from 21 recent-onset NT1 patients and from two control groups: group 1 with somatoform disorders, and group 2 patients with hypersomnia other than NT1, to control for any potential effect of sleep disturbances on CSF composition. To achieve an optimal proteomic coverage analysis, the twelve most abundant CSF proteins were depleted, and samples were analyzed by nano-flow liquid chromatography tandem mass spectrometry (nano-LC-MS/MS) using the latest generation of hybrid Orbitrap mass spectrometer. Our study allowed the identification and quantification of up to 1943 proteins, providing a remarkably deep analysis of the CSF proteome. Interestingly, gene set enrichment analysis indicated that the complement and coagulation systems were enriched and significantly activated in NT1 patients in both cohorts analyzed. Notably, the lectin and alternative complement pathway as well as the downstream lytic membrane attack complex were congruently increased in NT1. Our data suggest that the complement dysregulation in NT1 patients can contribute to immunopathology either by directly promoting tissue damage or as part of local inflammatory responses. We therefore reveal an altered composition of the CSF proteome in NT1 patients, which points to an ongoing inflammatory process contributed, at least in part, by the complement system.
HostingRepository	PRIDE
AnnounceDate	2023-04-06
AnnouncementXML	Submission_2023-04-06_08:20:20.474.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	EmmanuelleMouton Barbosa
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-24 04:45:09	ID requested
⏵ 1	2023-04-06 08:20:20	announced

Dataset with its publication pending

submitter keyword: Neuroimmunology, Coagulation system, Cerebrospinal fluid, Complement system, Immune response,Narcolepsy type 1, Proteomics

RollandLiblau
contact affiliation	Toulouse Institute for infectious and inflammatory diseases (Infinity), University of Toulouse, CNRS, INSERM, UPS, Toulouse, France. Department of Immunology, Toulouse University Hospitals, Toulouse, France.
contact email	roland.liblau@inserm.fr
lab head
EmmanuelleMouton Barbosa
contact affiliation	IPBS CNRS
contact email	emmanuelle.mouton@ipbs.fr
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/04/PXD041093

PRIDE project URI

• PRIDE
  1. PXD041093
     1. Label: PRIDE project
     2. Name: Cerebrospinal fluid proteomics in recent-onset Narcolepsy type 1 reveals activation of the complement system