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

半乳糖（Gal）缺陷型铰链区O-聚糖的IgA 1在伊加肾病（IgAN）中起关键作用。为了表征与IgAN有关的IgA 1，应分析O-聚糖的微异质性和附着位点。在这项研究中，IgAN患者和健康对照（HC）的血清IgA 1分别进行了分析，以确定糖基化模式和糖基化位点，使用高分辨率质谱（MS）。尽管来自HC的IgA 1含有一些缺乏Gal的O-聚糖，但来自IgAN患者的IgA 1中缺乏Gal的O-聚糖的量大于来自HC的IgA 1 O-聚糖的量。串联质谱显示，Gal缺陷型O-聚糖的位点主要包括IgA 1中的三个位点，IgA 1来自IgAN患者，IgA 1来自HC。本研究首次明确鉴定了IgAN患者IgA 1上的O-糖基化，包括位点附着。我们的协议提供了有用的信息相关的IgAN的发病机制，通过识别不同的O-糖基化模式。

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.