Complement system activation is a plasma biomarker signature during malaria in pregnancy

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

doi:10.3390/genes14081624

Complement system activation is a plasma biomarker signature during malaria in pregnancy

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

^*Corresponding author for this work

School of Natural Sciences

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

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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.

Original language	English
Article number	1624
Pages (from-to)	1-20
Number of pages	20
Journal	Genes
Volume	14
Issue number	8
DOIs	https://doi.org/10.3390/genes14081624
Publication status	Published - Aug 2023

Bibliographical note

Copyright the Author(s) 2023. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

biomarkers
complement system
malaria
malaria in pregnancy
plasma proteomics
Plasmodium berghei
Plasmodium falciparum

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10.3390/genes14081624Licence: CC BY

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Santiago, V. F., Dombrowski, J. G., Kawahara, R., Rosa-Fernandes, L., Mule, S. N., Murillo, O., Santana, T. V., Coutinho, J. V. P., Macedo-da-Silva, J., Lazari, L. C., Peixoto, E. P. M., Ramirez, M. I., Larsen, M. R., Marinho, C. R. F., & Palmisano, G. (2023). Complement system activation is a plasma biomarker signature during malaria in pregnancy. Genes, 14(8), 1-20. Article 1624. https://doi.org/10.3390/genes14081624

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title = "Complement system activation is a plasma biomarker signature during malaria in pregnancy",

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.",

keywords = "biomarkers, complement system, malaria, malaria in pregnancy, plasma proteomics, Plasmodium berghei, Plasmodium falciparum",

author = "Santiago, {Veronica Feijoli} and Dombrowski, {Jamille Gregorio} and Rebeca Kawahara and Livia Rosa-Fernandes and Mule, {Simon Ngao} and Oscar Murillo and Santana, {Thais Viggiani} and Coutinho, {Joao Victor Paccini} and Janaina Macedo-da-Silva and Lazari, {Lucas Cardoso} and Peixoto, {Erika Paula Machado} and Ramirez, {Marcel Ivan} and Larsen, {Martin R.} and Marinho, {Cl{\'a}udio Romero Farias} and Giuseppe Palmisano",

note = "Copyright the Author(s) 2023. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",

year = "2023",

month = aug,

doi = "10.3390/genes14081624",

language = "English",

volume = "14",

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Santiago, VF, Dombrowski, JG, Kawahara, R , Rosa-Fernandes, L, Mule, SN, Murillo, O, Santana, TV, Coutinho, JVP, Macedo-da-Silva, J, Lazari, LC, Peixoto, EPM, Ramirez, MI, Larsen, MR, Marinho, CRF & Palmisano, G 2023, 'Complement system activation is a plasma biomarker signature during malaria in pregnancy', Genes, vol. 14, no. 8, 1624, pp. 1-20. https://doi.org/10.3390/genes14081624

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T1 - Complement system activation is a plasma biomarker signature during malaria in pregnancy

AU - Santiago, Veronica Feijoli

AU - Dombrowski, Jamille Gregorio

AU - Kawahara, Rebeca

AU - Rosa-Fernandes, Livia

AU - Mule, Simon Ngao

AU - Murillo, Oscar

AU - Santana, Thais Viggiani

AU - Coutinho, Joao Victor Paccini

AU - Macedo-da-Silva, Janaina

AU - Lazari, Lucas Cardoso

AU - Peixoto, Erika Paula Machado

AU - Ramirez, Marcel Ivan

AU - Larsen, Martin R.

AU - Marinho, Cláudio Romero Farias

AU - Palmisano, Giuseppe

N1 - Copyright the Author(s) 2023. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2023/8

Y1 - 2023/8

N2 - 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.

AB - 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.

KW - biomarkers

KW - complement system

KW - malaria

KW - malaria in pregnancy

KW - plasma proteomics

KW - Plasmodium berghei

KW - Plasmodium falciparum

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DO - 10.3390/genes14081624

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SN - 2073-4425

VL - 14

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EP - 20

JO - Genes

JF - Genes

IS - 8

M1 - 1624

ER -

Complement system activation is a plasma biomarker signature during malaria in pregnancy

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