D3.347 - AllergoOncology: a systematic review of the impact of glycosylation on IgE antibody structure function and mechanisms of disease

The impact of human IgE glycosylation on structure, function, and disease mechanisms is not fully elucidated, with heterogeneity across existing studies. Previous reviews on IgE glycosylation focus on topics such as health and disease, FcεR binding, or functional impact.

We conducted the first systematic review of human IgE glycosylation, utilising the PRISMA guidelines where we sought to define the current consensus on roles of glycosylation on IgE structure, biology and disease.

Despite diverse analytical methodologies, biological sources, expression systems and the sparsity of data on IgE antibodies from non-allergic individuals, evidence indicates differential glycosylation profiles may exist for IgE, particularly in allergic disease. Such glycosylation patterns may have functional impact, and contribute to IgE-mediated hypersensitivities and atopic diseases. Outside of allergy, dysregulated terminal glycan structures, including sialic acid, may regulate IgE metabolism, whilst specific glycan sites such as N394 may contribute to stabilising IgE structure. Alterations to these sites likely  influences both structure and IgE-FcεR interactions.

Our findings highlight critical IgE glycosylation attributes in health and disease within this systematic review that may be exploitable for therapeutic intervention. Presence of potential differential glycosylation may indicate potential novel biomarkers, with potential to shed further light on the pathology of IgE-mediated disease. Targeting of specific residues within the IgE glycome may allow for modulation of IgE function. Finally, we highlight the need for novel analytics to explore pertinent research avenues.