Higher MRI lesion load in multiple sclerosis is related to the N-glycosylation changes of cerebrospinal fluid immunoglobulin G

•The composition of IgG N-glycans modulates the IgG Fc effector functions.•Only CSF-IgG N-glycans are changed in MS.•CSF-IgG N-glycans changes are related to the biomarkers of intrathecal inflammation.•The N-glycan FA2[6]BG1 is associated with higher CNS radiological activity. Intrathecal clonal exp...

Full description

Saved in:
Bibliographic Details
Published in:Multiple sclerosis and related disorders 2023-11, Vol.79, p.104921-104921, Article 104921
Main Authors: Turčić, Ana, Radovani, Barbara, Vogrinc, Željka, Habek, Mario, Rogić, Dunja, Gabelić, Tereza, Zaninović, Ljiljana, Lauc, Gordan, Gudelj, Ivan
Format: Article
Language:English
Subjects:
autoimmune diseases
demyelinating diseases
immunoglobulin G
multiple sclerosis
N-glycosylation
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:•The composition of IgG N-glycans modulates the IgG Fc effector functions.•Only CSF-IgG N-glycans are changed in MS.•CSF-IgG N-glycans changes are related to the biomarkers of intrathecal inflammation.•The N-glycan FA2[6]BG1 is associated with higher CNS radiological activity. Intrathecal clonal expansion of antibody-producing plasma cells in multiple sclerosis (MS) perpetuates central nervous system injury and is associated with active demyelination. Immunoglobulin G (IgG) effector functions are modulated by linked N-glycan structures. The aim of the study was to detect potential differences in N-glycosylation of IgG in serum and cerebrospinal fluid (CSF) and total sera proteins between people with MS and those in whom the diagnosis of MS was excluded. Furthermore, we investigated the association with standard laboratory biomarkers of intrathecal inflammation as well as clinical and neuroradiological disease activity. This cross-sectional study included patients with suspected demyelinating disease. MS diagnosis was based on the 2017 McDonald criteria and controls were patients with excluded MS diagnosis. N-glycans were compared with Expanded Disability Status Scale (EDSS), magnetic resonance imaging (MRI) markers of disease activity and biomarkers of intrathecal inflammation (cell count, CSF-IgG concentration, percentage of intrathecal IgG, oligoclonal bands (OCB), virus-specific antibody index (MRZH reaction)). Differences between groups were observed only in the CSF-IgG N-glycome. In MS, the presence of bisecting N-acetylglucosamine (Padj=2.63E-05) and monogalactosylation (Padj=1.49E-06) were more abundant and associated with positive OCBs. N-glycans monogalactosylated at the α6 arm FA2[6]G1 (r=0.56) and FA2[6]BG1 (r=0.45) correlated with percentage of intrathecal IgG, but not total CSF-IgG. This trait was also more abundant in MRZH positive people with MS who had higher MRI lesion load (P=0.018) but unrelated to active lesions or EDSS. More abundant monogalactosylation of intrathecally synthesized IgG is the most prominent trait in MS and is associated with higher MRI lesion load.
ISSN:2211-0348
2211-0356
DOI:10.1016/j.msard.2023.104921