N-Glycosylation of Serum IgG and Total Glycoproteins in MAN1B1 Deficiency

J Proteome Res. 2015 Oct 2;14(10):4402-12. doi: 10.1021/acs.jproteome.5b00709. Epub 2015 Sep 24.

Abstract

MAN1B1-CDG has recently been characterized as a type II congenital disorder of glycosylation (CDG), disrupting not only protein N-glycosylation but also general Golgi morphology. Using our high-throughput, quantitative ultra-performance liquid chromatography assay, we achieved a detailed characterization of the glycosylation changes in both total serum glycoproteins and isolated serum IgG from ten previously reported MAN1B1-CDG patients. We have identified and quantified novel hybrid high-mannosylated MAN1B1-CDG-specific IgG glycans and found an increase of sialyl Lewis x (sLex) glycans on serum proteins of all patients. This increase in sLex has not been previously reported in any CDG. These findings may provide insight into the pathophysiology of this CDG.

Keywords: CDG; IgG; MAN1B1; N-glycans; biomarkers; glycomics; human serum; sialyl Lewis x; ultra performance liquid chromatography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood
  • Carbohydrate Sequence
  • Case-Control Studies
  • Chromatography, Liquid
  • Congenital Disorders of Glycosylation / blood*
  • Congenital Disorders of Glycosylation / diagnosis*
  • Congenital Disorders of Glycosylation / genetics
  • Congenital Disorders of Glycosylation / pathology
  • Gene Expression Regulation
  • Glycomics
  • Glycoproteins / blood
  • Glycoproteins / genetics
  • Glycosylation
  • Golgi Apparatus / metabolism
  • Golgi Apparatus / pathology
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / genetics*
  • Lewis X Antigen / blood
  • Lewis X Antigen / genetics*
  • Molecular Sequence Data
  • alpha-Mannosidase / deficiency
  • alpha-Mannosidase / genetics*

Substances

  • Biomarkers
  • Glycoproteins
  • Immunoglobulin G
  • Lewis X Antigen
  • alpha-Mannosidase