Longevity & AgingHidden Asymmetric IgG Glycosylation Found in All Humans Drives Dengue Severity
Researchers developed WIgGWAM, an intact liquid chromatography/mass spectrometry method that profiles IgG antibody glycosylation while preserving the spatial pairing of glycans on each arm of the homodimeric Fc region. Analyzing plasma from healthy individuals, COVID-19 patients, and dengue patients, they found that asymmetrically glycosylated IgG1 antibodies—where each Fc protomer carries a different glycan—are universal in humans. Critically, the well-established link between IgG afucosylation and severe dengue was found to be driven not by symmetric afucosylation but by asymmetric monofucosylation. Engineered monofucosylated IgG1 antibodies behaved identically to fully afucosylated IgGs in binding FcγRIIIA and triggering immune effector functions, revealing a previously hidden layer of antibody biology with major implications for disease and therapeutics.
