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

Author

Listed:
  • Mary Lopez-Perez

    (University of Copenhagen)

  • Zakaria Seidu

    (University of Copenhagen
    University of Ghana
    University of Ghana
    University for Development Studies)

  • Mads Delbo Larsen

    (Sanquin Research
    Utrecht University
    Copenhagen University Hospital)

  • Wenjun Wang

    (Leiden University Medical Center)

  • Jan Nouta

    (Leiden University Medical Center)

  • Manfred Wuhrer

    (Leiden University Medical Center)

  • Gestur Vidarsson

    (Sanquin Research
    Utrecht University)

  • Michael F. Ofori

    (University of Ghana)

  • Lars Hviid

    (University of Copenhagen
    Rigshospitalet)

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.

Suggested Citation

  • Mary Lopez-Perez & Zakaria Seidu & Mads Delbo Larsen & Wenjun Wang & Jan Nouta & Manfred Wuhrer & Gestur Vidarsson & Michael F. Ofori & Lars Hviid, 2025. "Acquisition of Fc-afucosylation of PfEMP1-specific IgG is age-dependent and associated with clinical protection against malaria," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-55543-w
    DOI: 10.1038/s41467-024-55543-w
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    References listed on IDEAS

    as
    1. Alexander D. Douglas & Andrew R. Williams & Joseph J. Illingworth & Gathoni Kamuyu & Sumi Biswas & Anna L. Goodman & David H. Wyllie & Cécile Crosnier & Kazutoyo Miura & Gavin J. Wright & Carole A. Lo, 2011. "The blood-stage malaria antigen PfRH5 is susceptible to vaccine-inducible cross-strain neutralizing antibody," Nature Communications, Nature, vol. 2(1), pages 1-9, September.
    2. Mads Delbo Larsen & Mary Lopez-Perez & Emmanuel Kakra Dickson & Paulina Ampomah & Nicaise Tuikue Ndam & Jan Nouta & Carolien A. M. Koeleman & Agnes L. Hipgrave Ederveen & Benjamin Mordmüller & Ali Sal, 2021. "Afucosylated Plasmodium falciparum-specific IgG is induced by infection but not by subunit vaccination," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
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