PDF(Pubmed)
Abstract：
UNASSIGNED: Severe COVID and multisystem inflammatory syndrome (MIS-C) are characterized by excessive inflammatory cytokines/chemokines. In adults, disease severity is associated with SARS-CoV-2-specific IgG Fc afucosylation, which induces pro-inflammatory 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 cytokine/chemokine levels.
UNASSIGNED: We analyzed longitudinal (n=146) and cross-sectional (n=49) serum/plasma samples from adult and pediatric COVID patients, MIS-C patients, adult vaccinees, and adult and pediatric healthy controls. We developed methods for characterizing bulk and spike IgG Fc glycosylation by capillary electrophoresis (CE) and measured levels of ten inflammatory cytokines/chemokines by multiplexed ELISA.
UNASSIGNED: Spike IgG were more afucosylated than bulk IgG during acute adult COVID and MIS-C. We observed an opposite trend following vaccination, but it was not significant. Spike IgG were more galactosylated and sialylated and less bisected than bulk IgG during adult COVID, with similar trends observed during pediatric COVID/MIS-C and following SARS-CoV-2 vaccination. Spike IgG glycosylation changed with time following adult COVID 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 pro-inflammatory cytokines in adult COVID and MIS-C; and bisected spike IgG positively correlated with inflammatory cytokines/chemokines in multiple groups.
UNASSIGNED: 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 and MIS-C immunopathology.
UNASSIGNED: We analyzed longitudinal (n=146) and cross-sectional (n=49) serum/plasma samples from adult and pediatric COVID patients, MIS-C patients, adult vaccinees, and adult and pediatric healthy controls. We developed methods for characterizing bulk and spike IgG Fc glycosylation by capillary electrophoresis (CE) and measured levels of ten inflammatory cytokines/chemokines by multiplexed ELISA.
UNASSIGNED: Spike IgG were more afucosylated than bulk IgG during acute adult COVID and MIS-C. We observed an opposite trend following vaccination, but it was not significant. Spike IgG were more galactosylated and sialylated and less bisected than bulk IgG during adult COVID, with similar trends observed during pediatric COVID/MIS-C and following SARS-CoV-2 vaccination. Spike IgG glycosylation changed with time following adult COVID 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 pro-inflammatory cytokines in adult COVID and MIS-C; and bisected spike IgG positively correlated with inflammatory cytokines/chemokines in multiple groups.
UNASSIGNED: 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 and MIS-C immunopathology.
摘要：
■严重的COVID和多系统炎症综合征（MIS-C）的特征是过度的炎症细胞因子/趋化因子。在成年人中,疾病严重程度与SARS-CoV-2特异性IgGFc非岩藻糖基化有关，诱导先天性免疫细胞分泌促炎细胞因子。这项研究旨在定义成人和儿童SARS-CoV-2感染后以及成人SARS-CoV-2疫苗接种后的尖峰IgGFc糖基化以及聚糖修饰与细胞因子/趋化因子水平之间的关系。
■我们分析了成人和儿童COVID患者的纵向（n=146）和横截面（n=49）血清/血浆样本，MIS-C患者,成人疫苗接种者,以及成人和儿童健康对照。我们开发了通过毛细管电泳（CE）表征本体和尖峰IgGFc糖基化的方法，并通过多重ELISA测量了十种炎性细胞因子/趋化因子的水平。
■在急性成人COVID和MIS-C期间，尖刺IgG比散装IgG更无岩藻糖基化。我们在接种疫苗后观察到相反的趋势，但这并不重要。在成年COVID期间，穗状蛋白IgG的半乳糖基化和唾液酸化程度更高，并且比散装IgG的二等分程度更低，在儿科COVID/MIS-C和SARS-CoV-2疫苗接种期间观察到类似的趋势。成年COVID或接种疫苗后，尖峰IgG糖基化随时间变化。在MIS-C和接种后，脱藻糖基化的刺突IgG与炎症标志物呈负相关和正相关，分别；在成人COVID和MIS-C中，半乳糖基化和唾液酸化的spikeIgG与促炎细胞因子呈负相关；在多组中，spikeIgG与炎性细胞因子/趋化因子呈正相关。
■我们确定了之前未描述的尖峰IgG聚糖修饰与炎性细胞因子/趋化因子之间的关系，这扩大了我们对可能影响COVID和MIS-C免疫病理学的IgG糖基化变化的理解。
■我们分析了成人和儿童COVID患者的纵向（n=146）和横截面（n=49）血清/血浆样本，MIS-C患者,成人疫苗接种者,以及成人和儿童健康对照。我们开发了通过毛细管电泳（CE）表征本体和尖峰IgGFc糖基化的方法，并通过多重ELISA测量了十种炎性细胞因子/趋化因子的水平。
■在急性成人COVID和MIS-C期间，尖刺IgG比散装IgG更无岩藻糖基化。我们在接种疫苗后观察到相反的趋势，但这并不重要。在成年COVID期间，穗状蛋白IgG的半乳糖基化和唾液酸化程度更高，并且比散装IgG的二等分程度更低，在儿科COVID/MIS-C和SARS-CoV-2疫苗接种期间观察到类似的趋势。成年COVID或接种疫苗后，尖峰IgG糖基化随时间变化。在MIS-C和接种后，脱藻糖基化的刺突IgG与炎症标志物呈负相关和正相关，分别；在成人COVID和MIS-C中，半乳糖基化和唾液酸化的spikeIgG与促炎细胞因子呈负相关；在多组中，spikeIgG与炎性细胞因子/趋化因子呈正相关。
■我们确定了之前未描述的尖峰IgG聚糖修饰与炎性细胞因子/趋化因子之间的关系，这扩大了我们对可能影响COVID和MIS-C免疫病理学的IgG糖基化变化的理解。
