Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands.
Front Immunol. 2018 Oct 23;9:2436. doi: 10.3389/fimmu.2018.02436. eCollection 2018.
The -glycosylation of immunoglobulin (Ig) G, the major antibody in the circulation of human adults, is well known for its influence on antibody effector functions and its alterations with various diseases. In contrast, knowledge on the role of glycans attached to IgA, which is a key immune defense agent in secretions, is very scarce. In this study we aimed to characterize the glycosylation of salivary (secretory) IgA, including the IgA joining chain (JC), and secretory component (SC) and to compare IgA and IgG glycosylation between human plasma and saliva samples to gain a first insight into oral cavity-specific antibody glycosylation. Plasma and whole saliva were collected from 19 healthy volunteers within a 2-h time window. IgG and IgA were affinity-purified from the two biofluids, followed by tryptic digestion and nanoLC-ESI-QTOF-MS(/MS) analysis. Saliva-derived IgG exhibited a slightly lower galactosylation and sialylation as compared to plasma-derived IgG. Glycosylation of IgA1, IgA2, and the JC showed substantial differences between the biofluids, with salivary proteins exhibiting a higher bisection, and lower galactosylation and sialylation as compared to plasma-derived IgA and JC. Additionally, all seven -glycosylation sites, characterized on the SC of secretory IgA in saliva, carried highly fucosylated and fully galactosylated diantennary -glycans. This study lays the basis for future research into the functional role of salivary Ig glycosylation as well as its biomarker potential.
免疫球蛋白(Ig)G 的 -糖基化是众所周知的,它会影响抗体的效应功能,并在各种疾病中发生改变。相比之下,对于附着在 IgA 上的聚糖的作用知之甚少,IgA 是分泌液中的主要免疫防御剂。在本研究中,我们旨在描述唾液(分泌型)IgA 的糖基化,包括 IgA 连接链(JC)和分泌成分(SC),并比较人血浆和唾液样本中 IgA 和 IgG 的糖基化,以初步了解口腔特异性抗体糖基化。在 2 小时的时间窗口内,从 19 名健康志愿者中采集了血浆和全唾液。从两种生物流体中亲和纯化 IgG 和 IgA,然后进行胰蛋白酶消化和纳升液相色谱-电喷雾-四极杆飞行时间质谱(/ MS)分析。与血浆来源的 IgG 相比,唾液来源的 IgG 表现出稍微较低的半乳糖基化和唾液酸化。IgA1、IgA2 和 JC 的糖基化在两种生物流体之间存在很大差异,唾液蛋白的二分叉程度更高,半乳糖基化和唾液酸化程度更低,与血浆来源的 IgA 和 JC 相比。此外,唾液分泌型 IgA 的 SC 上所鉴定的七个 -糖基化位点均带有高度岩藻糖基化和完全半乳糖基化的二天线 -聚糖。本研究为进一步研究唾液 Ig 糖基化的功能作用及其作为生物标志物的潜力奠定了基础。