Afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity
Mads Delbo Larsen1,2,*, View ORCID ProfileErik L. de Graaf1,2,*, Myrthe E. Sonneveld1,2,*, View ORCID ProfileH. Rosina Plomp3, Jan Nouta3, View ORCID ProfileWilliann...
Science 26 Feb 2021:
Vol. 371, Issue 6532, eabc8378
DOI: 10.1126/science.abc8378
Structured Abstract
INTRODUCTION
Antibody function is often considered static and mostly determined by isotype and subclass. The conserved N-linked glycan at position 297 in the Fc domain of immunoglobulin G (IgG) is essential for an antibody’s effector functions. Moreover, this glycan is highly variable and functionally relevant, especially for the core fucose moiety. IgG lacking core fucosylation (afucosylated IgG) causes increased antibody-dependent cellular cytotoxicity (ADCC) through highly increased IgG-Fc receptor IIIa (FcγRIIIa) affinity. Despite constant levels of total plasma IgG-Fc fucosylation above 90%, specific IgG responses with low core fucosylation have been sporadically reported. These are directed against alloantigens on blood cells and glycoproteins of HIV and dengue virus. In this study, we investigated the induction of afucosylated IgG to various antigens and delineated its dynamics and proinflammatory potential in COVID-19.
RATIONALE
Afucosylated IgG responses have only been found in various alloimmune responses against cellular blood groups and two enveloped viruses. Therefore, we tested the hypothesis that foreign surface–exposed, membrane-embedded proteins induce a specific B cell response that results in afucosylated IgG. We compared immune responses to natural infections by enveloped viruses and nonenveloped viruses, protein subunit vaccination, and live attenuated virus vaccinations. We also assessed the relation to the clinical outcome of such a response in COVID-19.
