tetano
Editor, Senior Moderator
Nat Immunol
. 2020 Nov 9.
doi: 10.1038/s41590-020-00828-7. Online ahead of print.
Proinflammatory IgG Fc structures in patients with severe COVID-19
Saborni Chakraborty[SUP] 1 [/SUP], Joseph Gonzalez[SUP] 1 [/SUP], Karlie Edwards[SUP] 1 [/SUP], Vamsee Mallajosyula[SUP] 2 [/SUP], Anthony S Buzzanco[SUP] 1 [/SUP], Robert Sherwood[SUP] 3 [/SUP], Cindy Buffone[SUP] 1 [/SUP], Nimish Kathale[SUP] 1 [/SUP], Susan Providenza[SUP] 1 [/SUP], Markus M Xie[SUP] 1 [/SUP], Jason R Andrews[SUP] 1 [/SUP], Catherine A Blish[SUP] 1 4 [/SUP], Upinder Singh[SUP] 1 5 [/SUP], Haley Dugan[SUP] 6 [/SUP], Patrick C Wilson[SUP] 6 [/SUP], Tho D Pham[SUP] 7 [/SUP], Scott D Boyd[SUP] 8 9 [/SUP], Kari C Nadeau[SUP] 9 [/SUP], Benjamin A Pinsky[SUP] 1 8 [/SUP], Sheng Zhang[SUP] 3 [/SUP], Matthew J Memoli[SUP] 10 [/SUP], Jeffery K Taubenberger[SUP] 10 11 [/SUP], Tasha Morales[SUP] 12 [/SUP], Jeffrey M Schapiro[SUP] 12 [/SUP], Gene S Tan[SUP] 13 14 [/SUP], Prasanna Jagannathan[SUP] 1 5 [/SUP], Taia T Wang[SUP] 15 16 17 [/SUP]
Affiliations
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.
. 2020 Nov 9.
doi: 10.1038/s41590-020-00828-7. Online ahead of print.
Proinflammatory IgG Fc structures in patients with severe COVID-19
Saborni Chakraborty[SUP] 1 [/SUP], Joseph Gonzalez[SUP] 1 [/SUP], Karlie Edwards[SUP] 1 [/SUP], Vamsee Mallajosyula[SUP] 2 [/SUP], Anthony S Buzzanco[SUP] 1 [/SUP], Robert Sherwood[SUP] 3 [/SUP], Cindy Buffone[SUP] 1 [/SUP], Nimish Kathale[SUP] 1 [/SUP], Susan Providenza[SUP] 1 [/SUP], Markus M Xie[SUP] 1 [/SUP], Jason R Andrews[SUP] 1 [/SUP], Catherine A Blish[SUP] 1 4 [/SUP], Upinder Singh[SUP] 1 5 [/SUP], Haley Dugan[SUP] 6 [/SUP], Patrick C Wilson[SUP] 6 [/SUP], Tho D Pham[SUP] 7 [/SUP], Scott D Boyd[SUP] 8 9 [/SUP], Kari C Nadeau[SUP] 9 [/SUP], Benjamin A Pinsky[SUP] 1 8 [/SUP], Sheng Zhang[SUP] 3 [/SUP], Matthew J Memoli[SUP] 10 [/SUP], Jeffery K Taubenberger[SUP] 10 11 [/SUP], Tasha Morales[SUP] 12 [/SUP], Jeffrey M Schapiro[SUP] 12 [/SUP], Gene S Tan[SUP] 13 14 [/SUP], Prasanna Jagannathan[SUP] 1 5 [/SUP], Taia T Wang[SUP] 15 16 17 [/SUP]
Affiliations
- PMID: 33169014
- DOI: 10.1038/s41590-020-00828-7
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.