Acquisition of Fc-afucosylation of PfEMP1-specific IgG is age-dependent and associated with clinical protection against malaria

Mary Lopez-Perez, Zakaria Seidu, Mads Delbo Larsen, Wenjun Wang, Jan Nouta, Manfred Wuhrer, Gestur Vidarsson, Michael F Ofori, Lars Hviid

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Abstract

Protective immunity to malaria depends on acquisition of parasite-specific antibodies, with Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) being one of the most important target antigens. The effector functions of PfEMP1-specific IgG include inhibition of infected erythrocyte (IE) sequestration and opsonization of IEs for cell-mediated destruction. IgG glycosylation modulates antibody functionality, with increased affinity to FcγRIIIa for IgG lacking fucose in the Fc region (Fc-afucosylation). We report here that selective Fc-afucosylation of PfEMP1-specific IgG1 increases with age in P. falciparum-exposed children and is associated with reduced risk of anemia, independent of the IgG levels. A similar association was found for children having PfEMP1-specific IgG1 inducing multiple effector functions against IEs, particularly those associated with antibody-dependent cellular cytotoxicity (ADCC) by NK cells. Our findings provide new insights regarding protective immunity to P. falciparum malaria and highlight the importance of cell-mediated destruction of IgG-opsonized IEs.

Original languageEnglish
Article number237
JournalNature Communications
Volume16
Issue number1
Number of pages12
ISSN2041-1723
DOIs
Publication statusPublished - 2025

Bibliographical note

© 2024. The Author(s).

Keywords

  • Humans
  • Immunoglobulin G/immunology
  • Malaria, Falciparum/immunology
  • Protozoan Proteins/immunology
  • Plasmodium falciparum/immunology
  • Child
  • Child, Preschool
  • Antibodies, Protozoan/immunology
  • Immunoglobulin Fc Fragments/immunology
  • Erythrocytes/parasitology
  • Antibody-Dependent Cell Cytotoxicity/immunology
  • Glycosylation
  • Female
  • Male
  • Infant
  • Fucose/metabolism
  • Age Factors
  • Killer Cells, Natural/immunology
  • Receptors, IgG/metabolism
  • Adolescent
  • Adult

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