Differential expression of plasma proteins in pregnant women exposed to Plasmodium falciparum malaria

In sub-Saharan Africa, pregnant women are at greater risk of malaria infection than non-pregnant adult women. 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 serum 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 can predict PAM or adverse malaria outcomes. Such biomarkers may also elucidate the pathophysiology of PAM. We observed that the IgG Fc receptor IIb (Uniprot ID P31994) and HO-1 (P09601) are consistently highly expressed in malaria-positive samples compared to samples from malaria-negative pregnant women. On the contrary, NRTN (Q99748) and IL-20 (Q9NYY1) were differentially expressed in the malaria-negative women. IL-20 exhibited the highest discriminatory power (AUC = 0.815), indicating a strong association with malaria status. These proteins should be considered for further evaluation as biomarkers of malaria-induced placental dysfunction in pregnant women. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was funded by InDevelops u-landsfond InDevelops u-landsfond grant to MKM and JG, African Academy of Sciences to JG, and the Swedish Research Council under the grant 2020-02258 to MKM. BNK is an EDCTP Fellow under EDCTP2 programme supported by the European Union grant number TMA2020CDF-3203-EndPAMAL. BNK has also received support from Terumo Life Science Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study protocol and the use of this well-characterized biobank of samples were approved by the Independent Ethics Research Committee (IERC) of Mount Kenya University (No# MKU/IERC/0543, MKU/IERC/2461). All study participants gave written informed consent before joining the study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.