The Human Blood N-Glycome: Unraveling Disease Glycosylation Patterns

Abstract

Most of the proteins in the circulation are Nglycosylated, shaping together the total blood N-glycome (TBNG). Glycosylation is known to affect protein function, stability, and clearance. The TBNG is influenced by genetic, environmental, and metabolic factors, in part epigenetically imprinted, and responds to a variety of bioactive signals including cytokines and hormones. Accordingly, physiological and pathological events are reflected in distinct TBNG signatures. Here, we assess the specificity of the emerging disease-associated TBNG signatures with respect to a number of key glycosylation motifs including antennarity, linkagespecific sialylation, fucosylation, as well as expression of complex, hybrid-type and oligomannosidic N-glycans, and show perplexing complexity of the glycomic dimension of the studied diseases. Perspectives are given regarding the protein-and site-specific analysis of N-glycosylation, and the dissection of underlying regulatory layers and functional roles of blood protein N-glycosylation.

Total plasma N-glycomic signature of SARS-CoV-2 infection

“…In this respect we would like to mention the elevated levels of α2,6-linked sialic acids as well as reduced levels of galactosylation of fucosylated, non-sialylated, di-antennary glycans (A2FS0G; Figure 4 B), the latter generally being linked to IgG glycosylation which showed reduced levels in a number of diverse diseases. 42 Therefore, we cannot exclude the possibility that the observed glycosylation profiles are not COVID-19 specific but represent more general phenotypes.…”