AUTHOR=Kanoi Bernard N. , Waweru Harrison , Kobia Francis M. , Mukala Joseph , Kirira Peter , Mogere Dominic , Gallini Radiosa , Ã…berg Mikael , Vatish Manu , Gitaka Jesse , Kamali-Moghaddam Masood TITLE=Plasma protein biomarkers of Plasmodium falciparum infection in pregnant women: a high-throughput proteomics study JOURNAL=Frontiers in Cellular and Infection Microbiology VOLUME=Volume 15 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2025.1594088 DOI=10.3389/fcimb.2025.1594088 ISSN=2235-2988 ABSTRACT=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.