Nat Immunol . Proinflammatory IgG Fc structures in patients with severe COVID-19

[tetano]

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 ¹ , Joseph Gonzalez ¹ , Karlie Edwards ¹ , Vamsee Mallajosyula ² , Anthony S Buzzanco ¹ , Robert Sherwood ³ , Cindy Buffone ¹ , Nimish Kathale ¹ , Susan Providenza ¹ , Markus M Xie ¹ , Jason R Andrews ¹ , Catherine A Blish ^{1 4} , Upinder Singh ^{1 5} , Haley Dugan ⁶ , Patrick C Wilson ⁶ , Tho D Pham ⁷ , Scott D Boyd ^{8 9} , Kari C Nadeau ⁹ , Benjamin A Pinsky ^{1 8} , Sheng Zhang ³ , Matthew J Memoli ¹⁰ , Jeffery K Taubenberger ^{10 11} , Tasha Morales ¹² , Jeffrey M Schapiro ¹² , Gene S Tan ^{13 14} , Prasanna Jagannathan ^{1 5} , Taia T Wang ^{15 16 17}



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.