Glycobiology of rheumatic diseases

Abstract

Glycosylation has a profound influence on protein activity and cell biology through a variety of mechanisms, such as protein stability, receptor interactions and signal transduction. In many rheumatic diseases, a shift in protein glycosylation occurs, and is associated with inflammatory processes and disease progression. For example, the Fc-glycan composition on (auto)antibodies is associated with disease activity, and the presence of additional glycans in the antigen-binding domains of some autoreactive B cell receptors can affect B cell activation. In addition, changes in synovial fibroblast cell-surface glycosylation can alter the synovial microenvironment and are associated with an altered inflammatory state and disease activity in rheumatoid arthritis. The development of our understanding of the role of glycosylation of plasma proteins (particularly (auto)antibodies), cells and tissues in rheumatic pathological conditions suggests that glycosylation-based interventions could be used in the treatment of these diseases.

Glycoproteome remodelling and granule-specificN-glycosylation accompany neutrophil granulopoiesis

“…Finally, the Ge and Se granules each hosted ∼200 N -glycoproteins carrying predominantly oligomannosidic- and less sialylated/fucosylated complex-type N -glycans. While traditionally regarded as an intracellular glyco-feature pertaining to immaturely-processed N -glycoproteins trafficking the secretory machinery, oligomannosylation is increasingly reported i) on mature (fully processed) neutrophil glycoproteins as comprehensively reviewed 4,20 , ii) to decorate the surface of neutrophils 41 and other blood 42 and epithelial 43,44 cells, and iii) to be elevated in cancer 45,46 and other neutrophil-related diseases 47 . Our study supports that oligomannosylation is a prominent feature of the Ge and Se compartments.…”

N-Glycosylation as a Modulator of Protein Conformation and Assembly in Disease

“…It thus comes as no surprise that defects in protein glycosylation are associated with a variety of diseases. We direct the reader to excellent reviews on glycosylation in cancer [ 43 , 44 , 45 , 46 , 47 , 48 ], neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, autism spectrum disorder, and schizophrenia [ 49 , 50 , 51 ], congenital disorders [ 52 , 53 ], infection, and inflammation [ 54 , 55 , 56 , 57 , 58 ]. To understand how the nature and conformation of the glycan can drastically change the interaction of a protein with another in the context of health and disease, we direct the reader to several review articles [ 47 , 59 , 60 , 61 ].…”

N-linked Fc glycosylation is not required for IgG-B-cell receptor function in a GC-derived B-cell line

“…To date, it has been extensively studied and shown that IgG-Fc glycan composition is highly variable and changes with age, sex, health, and disease 4 , 6 , 7 . Specific IgG-Fc glycosylation patterns lacking terminal galactoses have been identified, for example, in rheumatic (e.g., rheumatoid arthritis, systemic lupus erythematosus, and ANCA-associated vasculitis) and other inflammatory diseases and are clearly associated with inflammation and disease activity 8 . In addition, alterations in Fc glycosylation have recently been highlighted in studies of anti-spike protein IgG responses in patients with COVID-19, showing highly dynamic glycosylation patterns, including low core fucosylation that correlates with disease severity 9 – 11 .…”