Proinflammatory IgG Fc Structures in Patients with Severe COVID-19

Overview

Journal Nat Immunol

Date 2020 Nov 10

PMID 33169014

Citations 186

Authors

Saborni Chakraborty

Joseph Gonzalez

Karlie Edwards

Vamsee Mallajosyula

Anthony S Buzzanco

Robert Sherwood

Cindy Buffone

Nimish Kathale

Susan Providenza

Markus M Xie

Jason R Andrews

Catherine A Blish

Upinder Singh

Haley Dugan

Patrick C Wilson

Tho D Pham

Scott D Boyd

Kari C Nadeau

Benjamin A Pinsky

Sheng Zhang

Matthew J Memoli

Jeffery K Taubenberger

Tasha Morales

Jeffrey M Schapiro

Gene S Tan

Prasanna Jagannathan

Taia T Wang

Affiliations

Soon will be listed here.

Abstract

Severe acute respiratory syndrome coronavirus 2 infections can cause coronavirus disease 2019 (COVID-19), which manifests with a range of severities from mild illness to life-threatening pneumonia and multi-organ failure. Severe COVID-19 is characterized by an inflammatory signature, including high levels of inflammatory cytokines, alveolar inflammatory infiltrates and vascular microthrombi. Here we show that patients with severe COVID-19 produced a unique serologic signature, including an increased likelihood of IgG1 with afucosylated Fc glycans. This Fc modification on severe acute respiratory syndrome coronavirus 2 IgGs enhanced interactions with the activating Fcγ receptor FcγRIIIa; when incorporated into immune complexes, Fc afucosylation enhanced production of inflammatory cytokines by monocytes, including interleukin-6 and tumor necrosis factor. These results show that disease severity in COVID-19 correlates with the presence of proinflammatory IgG Fc structures, including afucosylated IgG1.

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