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Immunoglobulin G1 Fc glycosylation as an early hallmark of severe COVID-19.
Pongracz, Tamas; Nouta, Jan; Wang, Wenjun; van Meijgaarden, Krista E; Linty, Federica; Vidarsson, Gestur; Joosten, Simone A; Ottenhoff, Tom H M; Hokke, Cornelis H; de Vries, Jutte J C; Arbous, Sesmu M; Roukens, Anna H E; Wuhrer, Manfred.
  • Pongracz T; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands. Electronic address: t.pongracz@lumc.nl.
  • Nouta J; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands.
  • Wang W; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands.
  • van Meijgaarden KE; Department of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands.
  • Linty F; Department of Experimental Immunohematology, Sanquin Research, Amsterdam, Netherlands; Landsteiner Laboratory, Amsterdam University Medical Center, Amsterdam, Netherlands.
  • Vidarsson G; Department of Experimental Immunohematology, Sanquin Research, Amsterdam, Netherlands; Landsteiner Laboratory, Amsterdam University Medical Center, Amsterdam, Netherlands.
  • Joosten SA; Department of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands.
  • Ottenhoff THM; Department of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands.
  • Hokke CH; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands.
  • de Vries JJC; Department of Medical Microbiology, Leiden University Medical Center, Leiden, Netherlands.
  • Arbous SM; Department of Intensive Care, Leiden University Medical Center, Leiden, Netherlands.
  • Roukens AHE; Department of Intensive Care, Leiden University Medical Center, Leiden, Netherlands.
  • Wuhrer M; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands.
EBioMedicine ; 78: 103957, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1828375
ABSTRACT

BACKGROUND:

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.

METHODS:

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.

FINDINGS:

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.

INTERPRETATION:

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.

FUNDING:

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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study Limits: Humans Language: English Journal: EBioMedicine Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study Limits: Humans Language: English Journal: EBioMedicine Year: 2022 Document Type: Article