Kanoi Bernard N, Waweru Harrison, Kobia Francis M, Mukala Joseph, Kirira Peter, Mogere Dominic, Gallini Radiosa, Åberg Mikael, Vatish Manu, Gitaka Jesse, Kamali-Moghaddam Masood
Centre for Malaria Elimination, Institute of Tropical Medicine, Mount Kenya University, Thika, Kenya.
School of Public Health, Mount Kenya University, Thika, Kenya.
Front Cell Infect Microbiol. 2025 Jul 8;15:1594088. doi: 10.3389/fcimb.2025.1594088. eCollection 2025.
Pregnant women in sub-Saharan Africa face heightened susceptibility to malaria, with placental sequestration driving adverse outcomes. The infection may lead to pregnancy-associated malaria (PAM) because of the sequestration of -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.
Here, 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 infection during pregnancy, with future potential to inform diagnosis of PAM or adverse malaria outcomes. Such biomarkers may also elucidate the pathophysiology of PAM.
Using 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.
IL-20 emerged as a top candidate biomarker, warranting validation in large cohorts with placental histopathology.
撒哈拉以南非洲地区的孕妇感染疟疾的易感性更高，胎盘隔离会导致不良后果。由于受感染的红细胞在胎盘绒毛间隙中隔离，这种感染可能导致妊娠相关疟疾（PAM）。尽管有几种工具可用于诊断孕期疟疾感染，包括血液涂片显微镜检查、快速诊断测试和聚合酶链反应（PCR），但尚无检测胎盘感染以及由此推断与PAM相关的任何功能障碍的工具。因此，PAM，特别是胎盘感染，只能通过产后胎盘组织病理学来确诊。因此，迫切需要PAM的特异性血浆生物标志物。
在此，我们使用高通量邻近延伸分析来筛选暴露于疟疾的孕妇血浆中差异表达的蛋白质，这些蛋白质可能作为孕期感染的候选生物标志物，未来有可能为PAM或不良疟疾结局的诊断提供依据。此类生物标志物还可能阐明PAM的病理生理学。
使用邻近延伸分析（PEA），我们发现在疟疾阳性妊娠中，IgG Fc受体IIb（FCGR2B）和血红素加氧酶-1（HO-1）升高，而神经营养因子（NRTN）和白细胞介素-20下调。
白细胞介素-20成为顶级候选生物标志物，值得在有胎盘组织病理学的大型队列中进行验证。
