# Plasma protein biomarkers of Plasmodium falciparum infection in pregnant women: a high-throughput proteomics study

**Authors:** 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

PMC · DOI: 10.3389/fcimb.2025.1594088 · Frontiers in Cellular and Infection Microbiology · 2025-07-08

## TL;DR

This study identifies potential blood protein markers for malaria in pregnant women, which could help diagnose and understand the disease's impact on pregnancy.

## Contribution

The study introduces novel plasma protein biomarkers for detecting placental malaria during pregnancy using high-throughput proteomics.

## Key findings

- Elevated FCGR2B and HO-1 proteins were found in malaria-positive pregnancies.
- Neurturin (NRTN) and IL-20 were downregulated in malaria-positive pregnancies.
- IL-20 is highlighted as a top candidate biomarker for further validation.

## Abstract

Pregnant 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.

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 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.

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.

## Linked entities

- **Proteins:** FCGR2B (Fc gamma receptor IIb), HMOX1 (heme oxygenase 1), NRTN (neurturin), IL20 (interleukin 20)
- **Diseases:** Plasmodium falciparum malaria (MONDO:0005920), malaria (MONDO:0005136)

## Full-text entities

- **Genes:** IL20 (interleukin 20) [NCBI Gene 50604] {aka IL-20, IL10D, ZCYTO10}, HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}, FCGR2B (Fc gamma receptor IIb) [NCBI Gene 2213] {aka CD32, CD32B, FCG2, FCGR2, IGFR2}, NRTN (neurturin) [NCBI Gene 4902] {aka NTN}
- **Diseases:** Plasmodium falciparum infection (OMIM:248310), malaria (MESH:D008288), PAM (MESH:D020150), infection (MESH:D007239), placental infection (MESH:D010922)
- **Species:** Homo sapiens (human, species) [taxon 9606], Plasmodium falciparum (malaria parasite P. falciparum, species) [taxon 5833]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12279802/full.md

## References

35 references — full list in the complete paper: https://tomesphere.com/paper/PMC12279802/full.md

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Source: https://tomesphere.com/paper/PMC12279802