Acquisition of Fc-afucosylation of PfEMP1-specific IgG is age-dependent and associated with clinical protection against malaria
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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55543-w |
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| author | Mary Lopez-Perez Zakaria Seidu Mads Delbo Larsen Wenjun Wang Jan Nouta Manfred Wuhrer Gestur Vidarsson Michael F. Ofori Lars Hviid |
| author_facet | Mary Lopez-Perez Zakaria Seidu Mads Delbo Larsen Wenjun Wang Jan Nouta Manfred Wuhrer Gestur Vidarsson Michael F. Ofori Lars Hviid |
| author_sort | Mary Lopez-Perez |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-9670dab9dfce4dc78210d8ec5ca7db70 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-9670dab9dfce4dc78210d8ec5ca7db702025-01-05T12:38:47ZengNature PortfolioNature Communications2041-17232025-01-0116111210.1038/s41467-024-55543-wAcquisition of Fc-afucosylation of PfEMP1-specific IgG is age-dependent and associated with clinical protection against malariaMary Lopez-Perez0Zakaria Seidu1Mads Delbo Larsen2Wenjun Wang3Jan Nouta4Manfred Wuhrer5Gestur Vidarsson6Michael F. Ofori7Lars Hviid8Centre for translational Medicine and Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of CopenhagenCentre for translational Medicine and Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of CopenhagenImmunoglobulin Research Laboratory, Sanquin ResearchCenter for Proteomics and Metabolomics, Leiden University Medical CenterCenter for Proteomics and Metabolomics, Leiden University Medical CenterCenter for Proteomics and Metabolomics, Leiden University Medical CenterImmunoglobulin Research Laboratory, Sanquin ResearchDepartment of Immunology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of GhanaCentre for translational Medicine and Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of CopenhagenAbstract 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.https://doi.org/10.1038/s41467-024-55543-w |
| spellingShingle | Mary Lopez-Perez Zakaria Seidu Mads Delbo Larsen Wenjun Wang Jan Nouta Manfred Wuhrer Gestur Vidarsson Michael F. Ofori Lars Hviid Acquisition of Fc-afucosylation of PfEMP1-specific IgG is age-dependent and associated with clinical protection against malaria Nature Communications |
| title | Acquisition of Fc-afucosylation of PfEMP1-specific IgG is age-dependent and associated with clinical protection against malaria |
| title_full | Acquisition of Fc-afucosylation of PfEMP1-specific IgG is age-dependent and associated with clinical protection against malaria |
| title_fullStr | Acquisition of Fc-afucosylation of PfEMP1-specific IgG is age-dependent and associated with clinical protection against malaria |
| title_full_unstemmed | Acquisition of Fc-afucosylation of PfEMP1-specific IgG is age-dependent and associated with clinical protection against malaria |
| title_short | Acquisition of Fc-afucosylation of PfEMP1-specific IgG is age-dependent and associated with clinical protection against malaria |
| title_sort | acquisition of fc afucosylation of pfemp1 specific igg is age dependent and associated with clinical protection against malaria |
| url | https://doi.org/10.1038/s41467-024-55543-w |
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