新冠病毒刺突蛋白免疫球蛋白G Fc段N-聚糖改变与成人新型冠状病毒肺炎及儿童多系统炎症综合征的高炎症状态相关。
Altered Spike Immunoglobulin G Fc N-Linked Glycans Are Associated With Hyperinflammatory State in Adult Coronavirus Disease 2019 and Multisystem Inflammatory Syndrome in Children.
作者信息
Sherman Jacob D, Karmali Vinit, Kumar Bhoj, Simon Trevor W, Bechnak Sarah, Panjwani Anusha, Ciric Caroline R, Wang Dongli, Huerta Christopher, Johnson Brandi, Anderson Evan J, Rouphael Nadine, Collins Matthew H, Rostad Christina A, Azadi Parastoo, Scherer Erin M
机构信息
Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA.
出版信息
Open Forum Infect Dis. 2024 Oct 16;11(11):ofae626. doi: 10.1093/ofid/ofae626. eCollection 2024 Nov.
BACKGROUND
Severe coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome (MIS-C) are characterized by excessive inflammatory cytokines/chemokines. In adults, disease severity is associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulin G (IgG) Fc afucosylation, which induces proinflammatory cytokine secretion from innate immune cells. This study aimed to define spike IgG Fc glycosylation following SARS-CoV-2 infection in adults and children and following SARS-CoV-2 vaccination in adults and the relationships between glycan modifications and cytokines/chemokines.
METHODS
We analyzed longitudinal (n = 146) and cross-sectional (n = 49) serum/plasma samples from adult and pediatric COVID-19 patients, MIS-C patients, adult vaccinees, and adult and pediatric controls. We developed methods for characterizing bulk and spike IgG Fc glycosylation by capillary electrophoresis and measured levels of 10 inflammatory cytokines/chemokines by multiplexed enzyme-linked immunosorbent assay.
RESULTS
Spike IgG was more afucosylated than bulk IgG during acute adult COVID-19 and MIS-C. We observed an opposite trend following vaccination, but it was not significant. Spike IgG was more galactosylated and sialylated and less bisected than bulk IgG during adult COVID-19, with similar trends observed during pediatric COVID-19/MIS-C and following SARS-CoV-2 vaccination. Spike IgG glycosylation changed with time following adult COVID-19 or vaccination. Afucosylated spike IgG exhibited inverse and positive correlations with inflammatory markers in MIS-C and following vaccination, respectively; galactosylated and sialylated spike IgG inversely correlated with proinflammatory cytokines in adult COVID-19 and MIS-C; and bisected spike IgG positively correlated with inflammatory cytokines/chemokines in multiple groups.
CONCLUSIONS
We identified previously undescribed relationships between spike IgG glycan modifications and inflammatory cytokines/chemokines that expand our understanding of IgG glycosylation changes that may impact COVID-19 and MIS-C immunopathology.
背景
2019年冠状病毒病（COVID-19）重症和多系统炎症综合征（MIS-C）的特征是炎症细胞因子/趋化因子过多。在成人中，疾病严重程度与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）特异性免疫球蛋白G（IgG）Fc去岩藻糖基化有关，后者可诱导先天免疫细胞分泌促炎细胞因子。本研究旨在确定成人和儿童感染SARS-CoV-2后以及成人接种SARS-CoV-2疫苗后刺突IgG Fc糖基化情况，以及聚糖修饰与细胞因子/趋化因子之间的关系。
方法
我们分析了成人和儿童COVID-19患者、MIS-C患者、成人疫苗接种者以及成人和儿童对照的纵向（n = 146）和横断面（n = 49）血清/血浆样本。我们开发了通过毛细管电泳表征整体和刺突IgG Fc糖基化的方法，并通过多重酶联免疫吸附测定法测量了10种炎症细胞因子/趋化因子的水平。
结果
在成人急性COVID-19和MIS-C期间，刺突IgG比整体IgG的去岩藻糖基化程度更高。接种疫苗后我们观察到相反的趋势，但不显著。在成人COVID-19期间，刺突IgG比整体IgG的半乳糖基化和唾液酸化程度更高，平分型聚糖更少，在儿童COVID-19/MIS-C期间以及接种SARS-CoV-2疫苗后也观察到类似趋势。成人COVID-19或接种疫苗后，刺突IgG糖基化随时间变化。去岩藻糖基化的刺突IgG在MIS-C和接种疫苗后分别与炎症标志物呈负相关和正相关；半乳糖基化和唾液酸化的刺突IgG在成人COVID-19和MIS-C中与促炎细胞因子呈负相关；平分型刺突IgG在多个组中与炎症细胞因子/趋化因子呈正相关。
结论
我们确定了刺突IgG聚糖修饰与炎症细胞因子/趋化因子之间以前未描述的关系，这扩展了我们对可能影响COVID-19和MIS-C免疫病理学的IgG糖基化变化的理解。
Zotero 插件