IgG-mediated activities are regulated by IgG subclass, Fc glycosylation, and Type I and II Fcγ receptors on effector cells.

Afucosylation of IgG1 is a mechanism for enhancing activating/pro-inflammatory effector functions.

Afucosylation of IgG1 is associated with pathological inflammatory sequelae in severe COVID-19 and dengue disease.

Sialylated IgG1 is anti-inflammatory and therapeutic in a number of disease states, such as Kawasaki disease, immune thrombocytopenic purpura, and multisystem inflammatory syndrome in children.

The effector activity of IgG antibodies is regulated at several levels, including IgG subclass, modifications of the Fc glycan, and the distribution of Type I and II Fcγ receptors (FcγR) on effector cells. Here, we explore how Fc glycosylation, particularly sialylation and fucosylation, tunes cellular responses to immune complexes. We review the current understanding of the pathways and mechanisms underlying this biology, address FcγR in antigen presentation, and discuss aspects of the clinical understanding of Fc glycans in therapies and disease.

© 2022 Published by Elsevier Ltd.