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

具有半乳糖(Gal)缺陷铰链区O-糖链的IgA1在IgA肾病(IgAN)中起着关键作用。为了确定与IgAN相关的IgA1的特征，需要分析O-糖链的微异质性和附着位置。在这项研究中，分别分析了IgAN患者和健康对照组(HCS)的血清IgA1，以确定糖基化模式和糖基化位点。虽然HCS的IgA1含有一些半乳糖缺乏的O-糖链，但IgAN患者的IgA1的O-糖链数量多于HCS的IgA1O-糖链。串联MS分析表明，Gal缺失O-糖链的位点主要包括IgAN患者的IgA1和HCS的IgA1中的3个位点。这项研究首次明确鉴定了IgAN患者的O-糖基化，包括结合在IgA1上的位点。我们的方案通过鉴定不同的O-糖基化模式，为IgAN的发病机制提供了有用的信息。

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.