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

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.