Quantitative Modeling of IgG N-Glycosylation Profiles from Population Data

Glycosylation of immunoglobulin G (IgG) is a critical regulator of its functional properties. We present an original mathematical model, calibrated and validated using quantitative IgG N-glycosylation data from two independent cohorts, 915 individuals from Korčula Island and 890 individuals from Vis Island, Croatia, reported in prior studies. The datasets comprise relative glycan levels measured by ultrahigh-performance liquid chromatography (UHPLC), represented by 22 chromatographic peaks per individual. By fitting the model to these data, we estimated the total concentrations of seven key enzymes involved in glycan biosynthesis across four Golgi compartments. The model revealed an age-related decline in β-N-acetylglucosaminylglycopeptide β-1,4-galactosyltransferase (GalT) concentrations in both populations, emphasizing its essential role in driving age-dependent changes in IgG glycan profiles and underscoring its potential as a biomarker of aging.