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 and Lars Hviid ()
Additional contact information
Mary Lopez-Perez: University of Copenhagen
Zakaria Seidu: University of Copenhagen
Mads Delbo Larsen: Sanquin Research
Wenjun Wang: Leiden University Medical Center
Jan Nouta: Leiden University Medical Center
Manfred Wuhrer: Leiden University Medical Center
Gestur Vidarsson: Sanquin Research
Michael F. Ofori: University of Ghana
Lars Hviid: University of Copenhagen

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: 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.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-55543-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-55543-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-55543-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().