tetano
Editor, Senior Moderator
Sci Transl Med
. 2022 Jan 18;eabm7853.
doi: 10.1126/scitranslmed.abm7853. Online ahead of print.
Early non-neutralizing, afucosylated antibody responses are associated with COVID-19 severity
Saborni Chakraborty[SUP] #[/SUP][SUP] 1 [/SUP], Joseph C Gonzalez[SUP] #[/SUP][SUP] 1 2 [/SUP], Benjamin L Sievers[SUP] 3 [/SUP], Vamsee Mallajosyula[SUP] 4 [/SUP], Srijoni Chakraborty[SUP] 5 [/SUP], Megha Dubey[SUP] 6 [/SUP], Usama Ashraf[SUP] 1 [/SUP], Bowie Yik-Ling Cheng[SUP] 1 [/SUP], Nimish Kathale[SUP] 1 [/SUP], Kim Quyen Thi Tran[SUP] 1 [/SUP], Courtney Scallan[SUP] 1 [/SUP], Aanika Sinnott[SUP] 3 [/SUP], Arianna Cassidy[SUP] 7 [/SUP], Steven T Chen[SUP] 8 9 10 [/SUP], Terri Gelbart[SUP] 3 [/SUP], Fei Gao[SUP] 4 [/SUP], Yarden Golan[SUP] 11 [/SUP], Xuhuai Ji[SUP] 4 [/SUP], Seunghee Kim-Schulze[SUP] 8 [/SUP], Mary Prahl[SUP] 12 [/SUP], Stephanie L Gaw[SUP] 7 [/SUP], Sacha Gnjatic[SUP] 8 9 10 13 [/SUP], Thomas U Marron[SUP] 8 9 [/SUP], Miriam Merad[SUP] 8 9 10 13 [/SUP], Prabhu S Arunachalam[SUP] 4 [/SUP], Scott D Boyd[SUP] 14 [/SUP], Mark M Davis[SUP] 4 6 15 [/SUP], Marisa Holubar[SUP] 1 [/SUP], Chaitan Khosla[SUP] 16 [/SUP], Holden T Maecker[SUP] 4 [/SUP], Yvonne Maldonado[SUP] 17 [/SUP], Elizabeth D Mellins[SUP] 17 [/SUP], Kari C Nadeau[SUP] 18 [/SUP], Bali Pulendran[SUP] 4 [/SUP], Upinder Singh[SUP] 1 6 [/SUP], Aruna Subramanian[SUP] 1 [/SUP], Paul J Utz[SUP] 19 [/SUP], Robert Sherwood[SUP] 20 [/SUP], Sheng Zhang[SUP] 20 [/SUP], Prasanna Jagannathan[SUP] 1 6 [/SUP], Gene S Tan[SUP] #[/SUP][SUP] 3 21 [/SUP], Taia T Wang[SUP] #[/SUP][SUP] 1 6 22 [/SUP]
Affiliations
Abstract
A damaging inflammatory response is implicated in the pathogenesis of severe coronavirus disease 2019 (COVID-19), but mechanisms contributing to this response are unclear. In two prospective cohorts, early non-neutralizing, afucosylated IgG antibodies specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were associated with progression from mild to more severe COVID-19. In contrast to the antibody structures that were associated with disease progression, antibodies that were elicited by mRNA SARS-CoV-2 vaccines were instead highly fucosylated and enriched in sialylation, both modifications that reduce the inflammatory potential of IgG. To study the biology afucosylated IgG immune complexes, we developed an in vivo model that revealed that human IgG-Fc gamma receptor (FcγR) interactions could regulate inflammation in the lung. Afucosylated IgG immune complexes isolated from COVID-19 patients induced inflammatory cytokine production and robust infiltration of the lung by immune cells. By contrast, vaccine-elicited IgG did not promote an inflammatory lung response. Together, these results show that IgG-FcγR interactions are able to regulate inflammation in the lung and may define distinct lung activities associated with the IgG that are associated with severe COVID-19 and protection against infection with SARS-CoV-2.
. 2022 Jan 18;eabm7853.
doi: 10.1126/scitranslmed.abm7853. Online ahead of print.
Early non-neutralizing, afucosylated antibody responses are associated with COVID-19 severity
Saborni Chakraborty[SUP] #[/SUP][SUP] 1 [/SUP], Joseph C Gonzalez[SUP] #[/SUP][SUP] 1 2 [/SUP], Benjamin L Sievers[SUP] 3 [/SUP], Vamsee Mallajosyula[SUP] 4 [/SUP], Srijoni Chakraborty[SUP] 5 [/SUP], Megha Dubey[SUP] 6 [/SUP], Usama Ashraf[SUP] 1 [/SUP], Bowie Yik-Ling Cheng[SUP] 1 [/SUP], Nimish Kathale[SUP] 1 [/SUP], Kim Quyen Thi Tran[SUP] 1 [/SUP], Courtney Scallan[SUP] 1 [/SUP], Aanika Sinnott[SUP] 3 [/SUP], Arianna Cassidy[SUP] 7 [/SUP], Steven T Chen[SUP] 8 9 10 [/SUP], Terri Gelbart[SUP] 3 [/SUP], Fei Gao[SUP] 4 [/SUP], Yarden Golan[SUP] 11 [/SUP], Xuhuai Ji[SUP] 4 [/SUP], Seunghee Kim-Schulze[SUP] 8 [/SUP], Mary Prahl[SUP] 12 [/SUP], Stephanie L Gaw[SUP] 7 [/SUP], Sacha Gnjatic[SUP] 8 9 10 13 [/SUP], Thomas U Marron[SUP] 8 9 [/SUP], Miriam Merad[SUP] 8 9 10 13 [/SUP], Prabhu S Arunachalam[SUP] 4 [/SUP], Scott D Boyd[SUP] 14 [/SUP], Mark M Davis[SUP] 4 6 15 [/SUP], Marisa Holubar[SUP] 1 [/SUP], Chaitan Khosla[SUP] 16 [/SUP], Holden T Maecker[SUP] 4 [/SUP], Yvonne Maldonado[SUP] 17 [/SUP], Elizabeth D Mellins[SUP] 17 [/SUP], Kari C Nadeau[SUP] 18 [/SUP], Bali Pulendran[SUP] 4 [/SUP], Upinder Singh[SUP] 1 6 [/SUP], Aruna Subramanian[SUP] 1 [/SUP], Paul J Utz[SUP] 19 [/SUP], Robert Sherwood[SUP] 20 [/SUP], Sheng Zhang[SUP] 20 [/SUP], Prasanna Jagannathan[SUP] 1 6 [/SUP], Gene S Tan[SUP] #[/SUP][SUP] 3 21 [/SUP], Taia T Wang[SUP] #[/SUP][SUP] 1 6 22 [/SUP]
Affiliations
- PMID: 35040666
- DOI: 10.1126/scitranslmed.abm7853
Abstract
A damaging inflammatory response is implicated in the pathogenesis of severe coronavirus disease 2019 (COVID-19), but mechanisms contributing to this response are unclear. In two prospective cohorts, early non-neutralizing, afucosylated IgG antibodies specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were associated with progression from mild to more severe COVID-19. In contrast to the antibody structures that were associated with disease progression, antibodies that were elicited by mRNA SARS-CoV-2 vaccines were instead highly fucosylated and enriched in sialylation, both modifications that reduce the inflammatory potential of IgG. To study the biology afucosylated IgG immune complexes, we developed an in vivo model that revealed that human IgG-Fc gamma receptor (FcγR) interactions could regulate inflammation in the lung. Afucosylated IgG immune complexes isolated from COVID-19 patients induced inflammatory cytokine production and robust infiltration of the lung by immune cells. By contrast, vaccine-elicited IgG did not promote an inflammatory lung response. Together, these results show that IgG-FcγR interactions are able to regulate inflammation in the lung and may define distinct lung activities associated with the IgG that are associated with severe COVID-19 and protection against infection with SARS-CoV-2.