Complement System Activation Is a Plasma Biomarker Signature during Malaria in Pregnancy

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Santiago, Veronica Feijoli ; Dombrowski, Jamille Gregorio ; Kawahara, Rebeca ; Rosa-Fernandes, Livia ; Mule, Simon Ngao ; Murillo, Oscar ; Santana, Thais Viggiani ; Paccini Coutinho, Joao Victor ; Macedo-da-Silva, Janaina ; Lazari, Lucas Cardoso ; Machado Peixoto, Erika Paula ; Ramirez, Marcel Ivan ; Larsen, Martin R. ; Farias Marinho, Claudio Romero ; Palmisano, Giuseppe

• Document type: Journal article
• Source: GENES; v. 14, n. 8, p. 20-pg., 2023-08-01.

Abstract

Malaria in pregnancy (MiP) is a public health problem in malaria-endemic areas, contributing to detrimental outcomes for both mother and fetus. Primigravida and second-time mothers are most affected by severe anemia complications and babies with low birth weight compared to multigravida women. Infected erythrocytes (IE) reach the placenta, activating the immune response by placental monocyte infiltration and inflammation. However, specific markers of MiP result in poor outcomes, such as low birth weight, and intrauterine growth restriction for babies and maternal anemia in women infected with Plasmodium falciparum are limited. In this study, we identified the plasma proteome signature of a mouse model infected with Plasmodium berghei ANKA and pregnant women infected with Plasmodium falciparum infection using quantitative mass spectrometry-based proteomics. A total of 279 and 249 proteins were quantified in murine and human plasma samples, of which 28% and 30% were regulated proteins, respectively. Most of the regulated proteins in both organisms are involved in complement system activation during malaria in pregnancy. CBA anaphylatoxin assay confirmed the complement system activation by the increase in C3a and C4a anaphylatoxins in the infected plasma compared to non-infected plasma. Moreover, correlation analysis showed the association between complement system activation and reduced head circumference in newborns from Pf-infected mothers. The data obtained in this study highlight the correlation between the complement system and immune and newborn outcomes resulting from malaria in pregnancy. (AU)

• FAPESP's process: 21/14751-4 - Novel mass spectrometry-based technologies for post-translational modifications analysis
• Grantee: Simon Ngao Mule
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/15549-1 - Post-translational modifications in Chagas Disease biological processes and diagnostics: novel methodological approaches and biological applications
• Grantee: Giuseppe Palmisano
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 20/06747-4 - Study of the humoral immune response in recurrent infections by Plasmodium vivax in pregnant women from Amazon region
• Grantee: Cláudio Romero Farias Marinho
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/04923-0 - SARS-CoV-2 glycosylation: a blueprint structural insight for understanding COVID-19 pathogenesis
• Grantee: Giuseppe Palmisano
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/04032-5 - Dissecting the pathogenesis of Chagas Disease by deep glycomics and glycoproteomics approaches
• Grantee: Simon Ngao Mule
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 21/00140-3 - Understanding the role of protein arginylation in health and disease through analytical and biological approaches
• Grantee: Janaína Macedo da Silva
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 19/12068-5 - Identification of predictive biomarkers of placental dysfunction in Malaria
• Grantee: Jamille Gregório Dombrowski
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/20468-0 - Recrudescence of the malaria during pregnancy: effects and mechanisms
• Grantee: Cláudio Romero Farias Marinho
• Support Opportunities: Regular Research Grants