Altered Spike Immunoglobulin G Fc N-Linked Glycans Are Associated With Hyperinflammatory State in Adult Coronavirus Disease 2019 and Multisystem Inflammatory Syndrome in Children.

IF 3.8 4区 医学 Q2 IMMUNOLOGY
Open Forum Infectious Diseases Pub Date : 2024-10-16 eCollection Date: 2024-11-01 DOI:10.1093/ofid/ofae626
Jacob D Sherman, Vinit Karmali, Bhoj Kumar, Trevor W Simon, Sarah Bechnak, Anusha Panjwani, Caroline R Ciric, Dongli Wang, Christopher Huerta, Brandi Johnson, Evan J Anderson, Nadine Rouphael, Matthew H Collins, Christina A Rostad, Parastoo Azadi, Erin M Scherer
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引用次数: 0

Abstract

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.

尖峰免疫球蛋白 G Fc N 联糖蛋白的改变与成人冠状病毒病 2019 和儿童多系统炎症综合征的高炎症状态有关。
背景:2019年严重冠状病毒病(COVID-19)和多系统炎症综合征(MIS-C)的特点是炎性细胞因子/凝血因子过多。在成人中,疾病的严重程度与严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)特异性免疫球蛋白 G(IgG)的 Fc afucosyl 化有关,这种 Fc afucosyl 化会诱导先天性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 疫苗后的尖峰 IgG Fc 糖基化,以及糖修饰与细胞因子/造血因子之间的关系:我们分析了来自成人和儿童 COVID-19 患者、MIS-C 患者、成人疫苗接种者以及成人和儿童对照组的纵向(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大量和尖峰 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/凝血因子的水平:结果:在COVID-19和MIS-C急性成人接种期间,尖峰IgG比大量IgG有更多的afucosyl化。我们观察到接种疫苗后出现了相反的趋势,但并不显著。在成人 COVID-19 期间,尖峰 IgG 的半乳糖基化和糖基化程度高于大体 IgG,而双糖基化程度低于大体 IgG,在小儿 COVID-19/MIS-C 和接种 SARS-CoV-2 疫苗后也观察到类似的趋势。成人 COVID-19 或接种疫苗后,尖峰 IgG 的糖基化随着时间的推移而变化。在 MIS-C 和接种疫苗后,Afucosyl 化的尖峰 IgG 分别与炎症标记物呈反向和正向相关;在成人 COVID-19 和 MIS-C 中,半乳糖基化和硅氨酰化的尖峰 IgG 与促炎症细胞因子呈反向相关;在多个组中,双连接的尖峰 IgG 与炎症细胞因子/造血因子呈正向相关:我们发现了尖峰 IgG 糖基化修饰与炎性细胞因子/趋化因子之间以前未曾描述过的关系,这拓展了我们对可能影响 COVID-19 和 MIS-C 免疫病理学的 IgG 糖基化变化的认识。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Open Forum Infectious Diseases
Open Forum Infectious Diseases Medicine-Neurology (clinical)
CiteScore
6.70
自引率
4.80%
发文量
630
审稿时长
9 weeks
期刊介绍: Open Forum Infectious Diseases provides a global forum for the publication of clinical, translational, and basic research findings in a fully open access, online journal environment. The journal reflects the broad diversity of the field of infectious diseases, and focuses on the intersection of biomedical science and clinical practice, with a particular emphasis on knowledge that holds the potential to improve patient care in populations around the world. Fully peer-reviewed, OFID supports the international community of infectious diseases experts by providing a venue for articles that further the understanding of all aspects of infectious diseases.
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