Altered IgG glycosylation at COVID-19 diagnosis predicts disease severity

Data de publicação: Data Ahead of Print:

Autores da FMUP

  • Luís Filipe Gomes Malheiro

    Autor

Participantes de fora da FMUP

  • Vicente, Manuel M.
  • Alves, Ines
  • Gaifem, Joana
  • Rodrigues, Claudia S.
  • Fernandes, Angela
  • Dias, Ana M.
  • Stambuk, Jerko
  • Petrovic, Tea
  • Oliveira, Pedro
  • Ferreira-da-Silva, Frederico
  • Soares, Adriana
  • Seixas, Nair
  • Teixeira, Tiago
  • Abreu, Miguel M.
  • Lauc, Gordan
  • Castro, Rui Sarmento E.
  • Pinho, Salome S.

Unidades de investigação

Abstract

The nature of the immune responses associated with COVID-19 pathogenesis and disease severity, as well as the breadth of vaccine coverage and duration of immunity, is still unclear. Given the unpredictability for developing a severe/complicated disease, there is an urgent need in the field for predictive biomarkers of COVID-19. We have analyzed IgG Fc N-glycan traits of 82 SARS-CoV-2+ unvaccinated patients, at diagnosis, by nano-LC-ESI-MS. We determined the impact of IgG Fc glyco-variations in the induction of NK cells activation, further evaluating the association between IgG Fc N-glycans and disease severity/prognosis. We found that SARS-CoV-2+ individuals display, at diagnosis, variations in the glycans composition of circulating IgGs. Importantly, levels of galactose and sialic acid structures on IgGs are able to predict the development of a poor COVID-19 disease. Mechanistically, we demonstrated that a deficiency on galactose structures on IgG Fc in COVID-19 patients appears to induce NK cells activation associated with increased release of IFN-gamma and TNF-alpha, which indicates the presence of pro-inflammatory immunoglobulins and higher immune activation, associated with a poor disease course. This study brings to light a novel blood biomarker based on IgG Fc glycome composition with capacity to stratify patients at diagnosis.

Dados da publicação

ISSN/ISSNe:
0014-2980, 1521-4141

European Journal of Immunology  Wiley-VCH Verlag

Tipo:
Article
Páginas:
946-957
Link para outro recurso:
www.scopus.com

Citações Recebidas na Web of Science: 27

Citações Recebidas na Scopus: 27

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Keywords

  • Inflammation; agalactosylation; asialylation; COVID-19; IgG Fc glycosylation; SARS-CoV-2

Proyectos asociados

The impact of SARS-CoV-2 viral load on the mortality of hospitalized patients. A retrospective analysis

Investigador Principal: Luís Filipe Gomes Malheiro

Estudo Clínico Académico (SARS-CoV-2) . 2021

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