Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands.
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands.
EBioMedicine. 2022 Apr;78:103957. doi: 10.1016/j.ebiom.2022.103957. Epub 2022 Mar 22.
Immunoglobulin G1 (IgG1) effector functions are impacted by the structure of fragment crystallizable (Fc) tail-linked N-glycans. Low fucosylation levels on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein-specific IgG1 has been described as a hallmark of severe coronavirus disease 2019 (COVID-19) and may lead to activation of macrophages via immune complexes thereby promoting inflammatory responses, altogether suggesting involvement of IgG1 Fc glycosylation modulated immune mechanisms in COVID-19.
In this prospective, observational single center cohort study, IgG1 Fc glycosylation was analyzed by liquid chromatography-mass spectrometry following affinity capturing from serial plasma samples of 159 SARS-CoV-2 infected hospitalized patients.
At baseline close to disease onset, anti-S IgG1 glycosylation was highly skewed when compared to total plasma IgG1. A rapid, general reduction in glycosylation skewing was observed during the disease course. Low anti-S IgG1 galactosylation and sialylation as well as high bisection were early hallmarks of disease severity, whilst high galactosylation and sialylation and low bisection were found in patients with low disease severity. In line with these observations, anti-S IgG1 glycosylation correlated with various inflammatory markers.
Association of low galactosylation, sialylation as well as high bisection with disease severity and inflammatory markers suggests that further studies are needed to understand how anti-S IgG1 glycosylation may contribute to disease mechanism and to evaluate its biomarker potential.
This project received funding from the European Commission's Horizon2020 research and innovation program for H2020-MSCA-ITN IMforFUTURE, under grant agreement number 721815, and supported by Crowdfunding Wake Up To Corona, organized by the Leiden University Fund.
免疫球蛋白 G1（IgG1）的效应功能受片段可结晶（Fc）尾部连接的 N-糖基化的结构影响。严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）刺突（S）蛋白特异性 IgG1 的低岩藻糖基化水平已被描述为严重 2019 冠状病毒病（COVID-19）的标志，可能通过免疫复合物激活巨噬细胞，从而促进炎症反应，这一切都表明 IgG1 Fc 糖基化调节的免疫机制参与了 COVID-19。
在这项前瞻性、观察性的单中心队列研究中，通过从 159 例 SARS-CoV-2 感染住院患者的连续血浆样本中进行亲和捕获，用液相色谱-质谱法分析 IgG1 Fc 糖基化。
在接近疾病发病的基线时，与总血浆 IgG1 相比，抗-S IgG1 糖基化高度偏斜。在疾病过程中观察到糖基化偏斜的快速、普遍减少。低抗-S IgG1 半乳糖基化和唾液酸化以及高双分叉是疾病严重程度的早期标志，而低疾病严重程度的患者则发现高半乳糖基化和唾液酸化以及低双分叉。与这些观察结果一致，抗-S IgG1 糖基化与各种炎症标志物相关。
低半乳糖基化、唾液酸化以及高双分叉与疾病严重程度和炎症标志物相关，这表明需要进一步研究以了解抗-S IgG1 糖基化如何有助于疾病机制，并评估其作为生物标志物的潜力。
本项目得到了欧盟 Horizon2020 研究和创新计划的资助，该计划是 H2020-MSCA-ITN IMforFUTURE 的一部分，资助协议号为 721815，并得到了由莱顿大学基金组织的众筹“唤醒对抗新冠”的支持。
