[HTML][HTML] Proinflammatory IgG Fc structures in patients with severe COVID-19

S Chakraborty, J Gonzalez, K Edwards… - Nature …, 2021 - nature.com
S Chakraborty, J Gonzalez, K Edwards, V Mallajosyula, AS Buzzanco, R Sherwood…
Nature immunology, 2021nature.com
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 …
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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