Dataset Information

Neurodegeneration and humoral response proteins in cerebrospinal fluid associate with pediatric-onset multiple sclerosis -- Validation

ABSTRACT: The pathogenesis of multiple sclerosis (MS) remains to be elucidated. Pediatric-onset MS (POMS) represents the earliest stage of the disease. CSF proteins in POMS may therefore provide causal information. Therefore, the aim of the current study was to analyze CSF proteins in children with an initial CNS acquired demyelinating syndrome (ADS) and to make a comparison between POMS and monophasic ADS (mADS). Patients were selected from two prospective pediatric ADS studies. Liquid chromatography-mass spectrometry was performed in a Dutch discovery cohort (POMS n=28; mADS n=39). Parallel reaction monitoring-mass spectrometry was performed on selected proteins more abundant in POMS with ≥ 8 unique peptides in a combined Dutch and Canadian validation cohort (POMS n=48; mADS n=106).

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cerebrospinal Fluid

DISEASE(S): Multiple Sclerosis,Pediatric Onset

SUBMITTER: Christoph Stingl

LAB HEAD: Theo M. Luider

PROVIDER: PXD031022 | Pride | 2022-09-30

REPOSITORIES: Pride

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Publications

Neurodegeneration and humoral response proteins in cerebrospinal fluid associate with pediatric-onset multiple sclerosis and not monophasic demyelinating syndromes in childhood.

Bruijstens Arlette L AL Stingl Christoph C Güzel Coşkun C Stoop Marcel P MP Wong Yu Yi M YYM van Pelt E Daniëlle ED Banwell Brenda L BL Bar-Or Amit A Luider Theo M TM Neuteboom Rinze F RF

Multiple sclerosis (Houndmills, Basingstoke, England) 20220924 1

<h4>Background</h4>Pediatric-onset multiple sclerosis (POMS) represents the earliest stage of disease pathogenesis. Investigating the cerebrospinal fluid (CSF) proteome in POMS may provide novel insights into early MS processes.<h4>Objective</h4>To analyze CSF obtained from children at time of initial central nervous system (CNS) acquired demyelinating syndrome (ADS), to compare CSF proteome of those subsequently ascertained as having POMS versus monophasic acquired demyelinating syndrome (mADS) ...[more]

PMID: 36154753

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Project description:A quadrupole time-of-flight mass spectrometry coupled with a trapped ion mobility mass spectrometer operated in parallel accumulation-serial fragmentation mode has recently emerged as proteome profiling platform capable of providing four dimensional features of elution time, collision cross section, precursor and fragment ion masses of peptides. The PASEF mode has demonstrated its superior performance by providing nearly 100% ion sampling efficiency both in data-dependent acquisition and data-independent acquisition modes without sacrificing sensitivity. In addition, the substantial gain in selectivity has been proven in targeted measurements using PASEF integrated parallel reaction monitoring mode. However, because these are emerging technologies in the field of proteomics, their applicability to clinical samples has been less investigated. Cerebrospinal fluid is in direct contact with brain and has been shown to contain biomarkers related to a variety of neurological diseases although the proteomics data have been mainly generated using orbitrap-based mass spectrometers. Thus, we acquired in-depth proteome profiles of human CSF in DDA mode to generate a spectral library of 3,478 proteins. The benefit of applying the spectral library to PRM experiments was demonstrated by using CSF samples from 15 Alzheimer’s disease patients and 19 controls and utilizing the spectral library to determine elution times and ion mobility values of targeting peptide. Further, we acquired DIA data from the same CSF samples, and analyzed using the spectral library without additional efforts to generate study-specific library, which also resulted in sensitive protein identification compared to a library-free approach. Overall, we established resource of CSF proteome profiles with 4D features and demonstrated the significant gain for designing and analyzing targeted and DIA studies, which is expected to facilitate 4D proteomics of CSF to study various neurological disorders.

Dataset Information

Neurodegeneration and humoral response proteins in cerebrospinal fluid associate with pediatric-onset multiple sclerosis -- Validation

Publications

Neurodegeneration and humoral response proteins in cerebrospinal fluid associate with pediatric-onset multiple sclerosis and not monophasic demyelinating syndromes in childhood.

Similar Datasets

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