Proinflammatory IgG Fc structures in patients with severe COVID-19

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 ZhangMatthew J. Memoli, Jeffery K. Taubenberger, Tasha Morales, Jeffrey M. Schapiro, Gene S. Tan, Prasanna Jagannathan, Taia T. Wang

Research output: Contribution to journalArticlepeer-review

125 Scopus citations

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.

Original languageEnglish
Pages (from-to)67-73
Number of pages7
JournalNature Immunology
Volume22
Issue number1
DOIs
StatePublished - Jan 2021
Externally publishedYes

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