Plasma protein biomarkers of Plasmodium falciparum infection in pregnant women: a high-throughput proteomics study
IntroductionPregnant women in sub-Saharan Africa face heightened susceptibility to Plasmodium falciparum malaria, with placental sequestration driving adverse outcomes. The infection may lead to pregnancy-associated malaria (PAM) because of the sequestration of Plasmodium falciparum-infected erythro...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| author | Bernard N. Kanoi Harrison Waweru Francis M. Kobia Joseph Mukala Peter Kirira Dominic Mogere Radiosa Gallini Mikael Åberg Manu Vatish Jesse Gitaka Masood Kamali-Moghaddam |
| author_facet | Bernard N. Kanoi Harrison Waweru Francis M. Kobia Joseph Mukala Peter Kirira Dominic Mogere Radiosa Gallini Mikael Åberg Manu Vatish Jesse Gitaka Masood Kamali-Moghaddam |
| author_sort | Bernard N. Kanoi |
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| description | IntroductionPregnant women in sub-Saharan Africa face heightened susceptibility to Plasmodium falciparum malaria, with placental sequestration driving adverse outcomes. The infection may lead to pregnancy-associated malaria (PAM) because of the sequestration of Plasmodium falciparum-infected erythrocytes in the placental intervillous space. Although there are several tools for diagnosing malaria infection during pregnancy, including blood smear microscopic examination, rapid diagnostic tests, and PCR, there are no tools for detecting placental infection and, by extension, any dysfunction associated with PAM. Thus, PAM, specifically placental infection, can only be confirmed via postnatal placental histopathology. Therefore, there is an urgent need for specific plasma biomarkers of PAM.MethodsHere, we used the high throughput proximity extension assay to screen plasma from malaria-exposed pregnant women for differentially expressed proteins that may serve as candidate biomarkers of Plasmodium falciparum infection during pregnancy, with future potential to inform diagnosis of PAM or adverse malaria outcomes. Such biomarkers may also elucidate the pathophysiology of PAM.ResultsUsing proximity extension assay (PEA), we identified elevated IgG Fc receptor IIb (FCGR2B) and heme oxygenase-1 (HO-1) in malaria-positive pregnancies, while neurturin (NRTN) and IL-20 were downregulated.DiscussionIL-20 emerged as a top candidate biomarker, warranting validation in large cohorts with placental histopathology. |
| format | Article |
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| language | English |
| publishDate | 2025-07-01 |
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| spelling | doaj-art-a73792c41c6e436aa9d0212a2e6cc9d52025-07-08T05:26:42ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-07-011510.3389/fcimb.2025.15940881594088Plasma protein biomarkers of Plasmodium falciparum infection in pregnant women: a high-throughput proteomics studyBernard N. Kanoi0Harrison Waweru1Francis M. Kobia2Joseph Mukala3Peter Kirira4Dominic Mogere5Radiosa Gallini6Mikael Åberg7Manu Vatish8Jesse Gitaka9Masood Kamali-Moghaddam10Centre for Malaria Elimination, Institute of Tropical Medicine, Mount Kenya University, Thika, KenyaCentre for Malaria Elimination, Institute of Tropical Medicine, Mount Kenya University, Thika, KenyaCentre for Malaria Elimination, Institute of Tropical Medicine, Mount Kenya University, Thika, KenyaSchool of Public Health, Mount Kenya University, Thika, KenyaSchool of Pure and Applied Sciences, Mount Kenya University, Thika, KenyaSchool of Public Health, Mount Kenya University, Thika, KenyaDepartment of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, SwedenDepartment of Medical Sciences, Clinical Chemistry and SciLifeLab Affinity Proteomics, Uppsala University, Uppsala, SwedenNuffield Department of Women’s and Reproductive Health, University of Oxford, Oxford, United KingdomCentre for Malaria Elimination, Institute of Tropical Medicine, Mount Kenya University, Thika, KenyaDepartment of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, SwedenIntroductionPregnant women in sub-Saharan Africa face heightened susceptibility to Plasmodium falciparum malaria, with placental sequestration driving adverse outcomes. The infection may lead to pregnancy-associated malaria (PAM) because of the sequestration of Plasmodium falciparum-infected erythrocytes in the placental intervillous space. Although there are several tools for diagnosing malaria infection during pregnancy, including blood smear microscopic examination, rapid diagnostic tests, and PCR, there are no tools for detecting placental infection and, by extension, any dysfunction associated with PAM. Thus, PAM, specifically placental infection, can only be confirmed via postnatal placental histopathology. Therefore, there is an urgent need for specific plasma biomarkers of PAM.MethodsHere, we used the high throughput proximity extension assay to screen plasma from malaria-exposed pregnant women for differentially expressed proteins that may serve as candidate biomarkers of Plasmodium falciparum infection during pregnancy, with future potential to inform diagnosis of PAM or adverse malaria outcomes. Such biomarkers may also elucidate the pathophysiology of PAM.ResultsUsing proximity extension assay (PEA), we identified elevated IgG Fc receptor IIb (FCGR2B) and heme oxygenase-1 (HO-1) in malaria-positive pregnancies, while neurturin (NRTN) and IL-20 were downregulated.DiscussionIL-20 emerged as a top candidate biomarker, warranting validation in large cohorts with placental histopathology.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1594088/fullpregnancy-associated malariamalaria in pregnancybiomarkersPlasmodium falciparumproteomicsproximity extension assay (PEA) |
| spellingShingle | Bernard N. Kanoi Harrison Waweru Francis M. Kobia Joseph Mukala Peter Kirira Dominic Mogere Radiosa Gallini Mikael Åberg Manu Vatish Jesse Gitaka Masood Kamali-Moghaddam Plasma protein biomarkers of Plasmodium falciparum infection in pregnant women: a high-throughput proteomics study Frontiers in Cellular and Infection Microbiology pregnancy-associated malaria malaria in pregnancy biomarkers Plasmodium falciparum proteomics proximity extension assay (PEA) |
| title | Plasma protein biomarkers of Plasmodium falciparum infection in pregnant women: a high-throughput proteomics study |
| title_full | Plasma protein biomarkers of Plasmodium falciparum infection in pregnant women: a high-throughput proteomics study |
| title_fullStr | Plasma protein biomarkers of Plasmodium falciparum infection in pregnant women: a high-throughput proteomics study |
| title_full_unstemmed | Plasma protein biomarkers of Plasmodium falciparum infection in pregnant women: a high-throughput proteomics study |
| title_short | Plasma protein biomarkers of Plasmodium falciparum infection in pregnant women: a high-throughput proteomics study |
| title_sort | plasma protein biomarkers of plasmodium falciparum infection in pregnant women a high throughput proteomics study |
| topic | pregnancy-associated malaria malaria in pregnancy biomarkers Plasmodium falciparum proteomics proximity extension assay (PEA) |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1594088/full |
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