Molecular Characterization of Glycosylation on Immunoglobulins: Implication for Pathogenesis of IgA Nephropathy

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IgA1 with galactose (Gal)-deficient hinge-region O-glycans plays a key role in IgA nephropathy (IgAN). To characterize IgA1 involved with IgAN, O-glycan microheterogeneity and attachment sites should be analyzed. In this study, serum IgA1 from IgAN patients and healthy controls (HCs) was individually analyzed to define the glycosylation patterns and glycosylation sites using high-resolution mass spectrometry (MS). Although IgA1 from HCs contain some Gal-deficient O-glycans, the amount of Gal-deficient O-glycans in IgA1 from IgAN patients was greater than that in IgA1 O-glycans from HCs. Tandem MS revealed that the sites with Gal-deficient O-glycans included mainly three sites in IgA1 from IgAN patients as well as IgA1 from HCs. This study shows first definitive identification of O-glycosylation including sites attachment on IgA1 from IgAN patients. Our protocol provides useful information relevant to pathogenesis of IgAN through the identification of distinct O-glycosylation patterns.