MassIVE MSV000100808

Partial Public

The CNS compartmentalized IgG aggregates and glycosylation in multiple sclerosis contribute to oligoclonal bands and neuronal cytotoxicity

Subscribe Comment Convert Spectra Add Reanalysis

Description

Background: Oligoclonal bands (OCBs) are a hallmark of multiple sclerosis (MS), yet their molecular characteristics and pathogenic relevance remain incompletely understood. Recent evidence suggests that immunoglobulin G (IgG) aggregates and glycosylation may contribute to neuroinflammation and neuronal injury in MS. Methods: We analyzed paired cerebrospinal fluid (CSF) and plasma samples from MS patients and other neurological controls using transmission electron microscopy, protein aggregation assays, proteomics, isoelectric focusing immunoblotting, and western blots. Neuronal cytotoxicity was assessed using human iPSC-derived neurons and SH-SY5Y cells. IgG glycosylation was evaluated by enzymatic deglycosylation and lectin-based detection. Results: We identified large IgG aggregates (>100 nm) in MS CSF, which were absent in controls and induced complement-dependent neuronal apoptosis. These aggregates were enriched in OCBs and were disrupted by urea or glycine-HCl, resulting in the loss of OCBs. Proteomic analysis revealed enrichment of IgG subclasses and complement components in MS CSF. In addition, MS CSF contained significantly elevated levels of galactosylated and sialylated IgG compared to paired plasma. Enzymatic removal of glycans reduced both OCB intensity and neuronal cytotoxicity. Conclusions: Our findings demonstrate that CNS-compartmentalized IgG aggregates and glycosylation contribute to the formation of OCBs and neuronal cytotoxicity in MS. These results provide new insights into the molecular basis of OCBs and suggest that targeting IgG glycosylation or aggregation may offer novel therapeutic strategies for MS. [doi:10.25345/C57W67K5V] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Multiple sclerosis, IgG aggregates, glycosylation, oligoclonal bands, cerebrospinal fluid, neuronal cytotoxicity, complement activation, neuroinflammation, autoantibodies, protein aggregation ; DatasetType:Proteomics

Contact

Principal Investigators:
(in alphabetical order) 		Xiaoli Yu, University of Colorado Anschutz Medical Campus, United States
Submitting User: mdziecia
Number of Files:
Total Size:
Spectra:
Subscribers:
 
Owner Reanalyses
Experimental Design
    Conditions:
    Biological Replicates:
    Technical Replicates:
 
Identification Results
    Proteins (Human, Remapped):
    Proteins (Reported):
    Peptides:
    Variant Peptides:
    PSMs:
 
Quantification Results
    Differential Proteins:
    Quantified Proteins:
 
Browse Dataset Files
 
FTP Download Link (click to copy):

Species

Instrument

Modifications

- Dataset Reanalyses

+ Dataset History

Click here to queue conversion of this dataset's submitted spectrum files to open formats (e.g. mzML). This process may take some time.

When complete, the converted files will be available in the "ccms_peak" subdirectory of the dataset's FTP space (accessible via the "FTP Download" link to the right).
Number of distinct conditions across all analyses (original submission and reanalyses) associated with this dataset.

Distinct condition labels are counted across all files submitted in the "Metadata" category having a "Condition" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct biological replicates across all analyses (original submission and reanalyses) associated with this dataset.

Distinct replicate labels are counted across all files submitted in the "Metadata" category having a "BioReplicate" or "Replicate" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct technical replicates across all analyses (original submission and reanalyses) associated with this dataset.

The technical replicate count is defined as the maximum number of times any one distinct combination of condition and biological replicate was analyzed across all files submitted in the "Metadata" category. In the case of fractionated experiments, only the first fraction is considered.

"N/A" means no results of this type were submitted.
Originally identified proteins that were automatically remapped by MassIVE to proteins in the SwissProt human reference database.

"N/A" means no results of this type were submitted.
Number of distinct protein accessions reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct unmodified peptide sequences reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct peptide sequences (including modified variants or peptidoforms) reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Total number of peptide-spectrum matches (i.e. spectrum identifications) reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct proteins quantified across all analyses (original submission and reanalyses) associated with this dataset.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct proteins found to be differentially abundant in at least one comparison across all analyses (original submission and reanalyses) associated with this dataset.

A protein is differentially abundant if its change in abundance across conditions is found to be statistically significant with an adjusted p-value <= 0.05 and lists no issues associated with statistical tests for differential abundance.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
This dataset may not contain all raw spectra data as originally deposited in PRIDE. It has been imported to MassIVE for reanalysis purposes, so its spectra data here may consist solely of processed peak lists suitable for reanalysis with most software.