tetano
Editor, Senior Moderator
Open Forum Infect Dis
. 2024 Oct 16;11(11)
fae626.
doi: 10.1093/ofid/ofae626. eCollection 2024 Nov. Altered Spike Immunoglobulin G Fc N-Linked Glycans Are Associated With Hyperinflammatory State in Adult Coronavirus Disease 2019 and Multisystem Inflammatory Syndrome in Children
Jacob D Sherman[SUP] 1 [/SUP], Vinit Karmali[SUP] 1 [/SUP], Bhoj Kumar[SUP] 2 [/SUP], Trevor W Simon[SUP] 1 [/SUP], Sarah Bechnak[SUP] 1 [/SUP], Anusha Panjwani[SUP] 1 [/SUP], Caroline R Ciric[SUP] 3 [/SUP], Dongli Wang[SUP] 1 [/SUP], Christopher Huerta[SUP] 1 [/SUP], Brandi Johnson[SUP] 1 [/SUP], Evan J Anderson[SUP] 1 3 [/SUP], Nadine Rouphael[SUP] 1 [/SUP], Matthew H Collins[SUP] 1 [/SUP], Christina A Rostad[SUP] 3 [/SUP], Parastoo Azadi[SUP] 2 [/SUP], Erin M Scherer[SUP] 1 [/SUP]
Affiliations
Background: Severe coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome (MIS-C) are characterized by excessive inflammatory cytokines/chemokines. In adults, disease severity is associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulin G (IgG) Fc afucosylation, which induces proinflammatory cytokine secretion from innate immune cells. This study aimed to define spike IgG Fc glycosylation following SARS-CoV-2 infection in adults and children and following SARS-CoV-2 vaccination in adults and the relationships between glycan modifications and cytokines/chemokines.
Methods: We analyzed longitudinal (n = 146) and cross-sectional (n = 49) serum/plasma samples from adult and pediatric COVID-19 patients, MIS-C patients, adult vaccinees, and adult and pediatric controls. We developed methods for characterizing bulk and spike IgG Fc glycosylation by capillary electrophoresis and measured levels of 10 inflammatory cytokines/chemokines by multiplexed enzyme-linked immunosorbent assay.
Results: Spike IgG was more afucosylated than bulk IgG during acute adult COVID-19 and MIS-C. We observed an opposite trend following vaccination, but it was not significant. Spike IgG was more galactosylated and sialylated and less bisected than bulk IgG during adult COVID-19, with similar trends observed during pediatric COVID-19/MIS-C and following SARS-CoV-2 vaccination. Spike IgG glycosylation changed with time following adult COVID-19 or vaccination. Afucosylated spike IgG exhibited inverse and positive correlations with inflammatory markers in MIS-C and following vaccination, respectively; galactosylated and sialylated spike IgG inversely correlated with proinflammatory cytokines in adult COVID-19 and MIS-C; and bisected spike IgG positively correlated with inflammatory cytokines/chemokines in multiple groups.
Conclusions: We identified previously undescribed relationships between spike IgG glycan modifications and inflammatory cytokines/chemokines that expand our understanding of IgG glycosylation changes that may impact COVID-19 and MIS-C immunopathology.
Keywords: COVID-19; Fc; MIS-C; antibody glycosylation; inflammation.
. 2024 Oct 16;11(11)
fae626.doi: 10.1093/ofid/ofae626. eCollection 2024 Nov. Altered Spike Immunoglobulin G Fc N-Linked Glycans Are Associated With Hyperinflammatory State in Adult Coronavirus Disease 2019 and Multisystem Inflammatory Syndrome in Children
Jacob D Sherman[SUP] 1 [/SUP], Vinit Karmali[SUP] 1 [/SUP], Bhoj Kumar[SUP] 2 [/SUP], Trevor W Simon[SUP] 1 [/SUP], Sarah Bechnak[SUP] 1 [/SUP], Anusha Panjwani[SUP] 1 [/SUP], Caroline R Ciric[SUP] 3 [/SUP], Dongli Wang[SUP] 1 [/SUP], Christopher Huerta[SUP] 1 [/SUP], Brandi Johnson[SUP] 1 [/SUP], Evan J Anderson[SUP] 1 3 [/SUP], Nadine Rouphael[SUP] 1 [/SUP], Matthew H Collins[SUP] 1 [/SUP], Christina A Rostad[SUP] 3 [/SUP], Parastoo Azadi[SUP] 2 [/SUP], Erin M Scherer[SUP] 1 [/SUP]
Affiliations
- PMID: 39494457
- PMCID: PMC11528514
- DOI: 10.1093/ofid/ofae626
Background: Severe coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome (MIS-C) are characterized by excessive inflammatory cytokines/chemokines. In adults, disease severity is associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulin G (IgG) Fc afucosylation, which induces proinflammatory cytokine secretion from innate immune cells. This study aimed to define spike IgG Fc glycosylation following SARS-CoV-2 infection in adults and children and following SARS-CoV-2 vaccination in adults and the relationships between glycan modifications and cytokines/chemokines.
Methods: We analyzed longitudinal (n = 146) and cross-sectional (n = 49) serum/plasma samples from adult and pediatric COVID-19 patients, MIS-C patients, adult vaccinees, and adult and pediatric controls. We developed methods for characterizing bulk and spike IgG Fc glycosylation by capillary electrophoresis and measured levels of 10 inflammatory cytokines/chemokines by multiplexed enzyme-linked immunosorbent assay.
Results: Spike IgG was more afucosylated than bulk IgG during acute adult COVID-19 and MIS-C. We observed an opposite trend following vaccination, but it was not significant. Spike IgG was more galactosylated and sialylated and less bisected than bulk IgG during adult COVID-19, with similar trends observed during pediatric COVID-19/MIS-C and following SARS-CoV-2 vaccination. Spike IgG glycosylation changed with time following adult COVID-19 or vaccination. Afucosylated spike IgG exhibited inverse and positive correlations with inflammatory markers in MIS-C and following vaccination, respectively; galactosylated and sialylated spike IgG inversely correlated with proinflammatory cytokines in adult COVID-19 and MIS-C; and bisected spike IgG positively correlated with inflammatory cytokines/chemokines in multiple groups.
Conclusions: We identified previously undescribed relationships between spike IgG glycan modifications and inflammatory cytokines/chemokines that expand our understanding of IgG glycosylation changes that may impact COVID-19 and MIS-C immunopathology.
Keywords: COVID-19; Fc; MIS-C; antibody glycosylation; inflammation.