Elevated Levels of Soluble TNF Receptors 1 and 2 Correlate with Plasmodium falciparum Parasitemia in Pregnant Women: Potential Markers for Malaria-Associated Inflammation
Open accessAbstract
Plasmodium falciparum-infected erythrocytes (IEs) sequester in the intervillous space (IVS) of the placenta causing placental malaria (PM), a condition that increases a woman’s chances of having a low-birth-weight baby. Because IEs sequester, they frequently are not observed in peripheral blood smears, resulting in women with PM being misdiagnosed and thus not treated. Because sequestered IEs induce inflammation in the IVS, detection of inflammatory mediators in the peripheral blood may provide an approach for diagnosing PM. Two counterregulatory molecules, TNF-αR (TNFR) 1 and TNFR2, modulate the pathological effects of TNF-α. Levels of these soluble TNFRs (sTNFRs) are reported to be elevated in children with severe malaria, but it is unclear if they are increased in the peripheral blood of PM-positive women with asymptomatic infections. In this study, sTNFR levels were measured throughout the course of pregnancy, as well as at delivery, in women with asymptomatic infections and those who remained uninfected. Results showed that both sTNFRs were significantly increased in the peripheral blood of women with asymptomatic malaria (p < 0.0001) and were positively correlated with parasitemia (p < 0.0001 for sTNFR1 and p = 0.0046 for sTNFR2). Importantly, levels of sTNFR2 were elevated in the peripheral blood of women who were PM-positive but peripheral blood-smear negative (p = 0.0017). Additionally, sTNFR2 levels were elevated in the blood of malaria-positive women who delivered low-birth-weight babies. In vitro studies demonstrated that syncytiotrophoblasts were not a major source of sTNFR. These data suggest that sTNFR2 may be a valuable biomarker for detection of malaria-associated inflammation.
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Low birth weight due to intrauterine growth retardation is associated with maternal anaemia and elevated levels of cytokines.
“LBW due to IUGR is associated with maternal anaemia,83,85 and elevated levels of cytokines.70”
From Malaria in pregnancy. (2013) · cites this paper as [70]
Citation 70 is attached to the elevated-cytokine part of the sentence, not maternal anaemia. The Introduction links elevated TNF-α, a cytokine, to low birth weight, and the Results report elevated soluble TNF receptors in mothers of low-birth-weight babies. But the Discussion says low birth weight in this study was primarily due to prematurity; the paper does not establish the claimed association specifically for IUGR. (LLM, conf=0.86)
Experimental — accuracy not yet measuredCytokine responses such as Th1, Th2, interleukins, TNF and regulators, IFN gamma, and monocytes have been observed in pregnant women with malaria.
“Besides the antibody responses to VSAPAM, cytokine responses such as Th1, Th2, interleukins, TNF and regulators, IFN gamma,70–72 and monocytes73 have been observed in pregnant women with malaria.”
From Malaria in pregnancy. (2013) · cites this paper as [70]
TNF receptor II may be increased in women with submicroscopic infection.
“TNF receptor II may be increased in women with submicroscopic infection as well [81].”
From Diagnosing malaria in pregnancy: An update (2012) · cites this paper as [81]
PM is associated with inflammatory immune responses, with increased levels of soluble mediators like TNF-α, TNF receptor I, TNF receptor II and IL-10 in peripheral blood.
“PM is associated with inflammatory immune responses [75–79], with increased levels of soluble mediators like TNF-α, TNF receptor I, TNF receptor II and IL-10 in peripheral blood [80,81].”
From Diagnosing malaria in pregnancy: An update (2012) · cites this paper as [81]
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References 55 · Cited by 44
- Authors
- Thévenon, A. D., Zhou, J. A., Megnekou, R., Ako, S., Leke, R. G. F., & Taylor, D. W.
- Affiliations
- University of Hawaiʻi at Mānoa (US)
- AZ DataClinic, Inc. , Rockville, MD 20850
- Université de Yaoundé I (CM)
- Corresponding author
- Taylor, Diane Wallace
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-12-01
- Volume
- 185
- Issue
- 11
- Pages
- 7115-7122
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC2988086
- OpenAlex
- W2104702041
- Cited by
- 44
- References
- 55
- Citations by year
- 2025: 3 · 2024: 2 · 2022: 1 · 2021: 2 · 2019: 4 · 2018: 1 · 2017: 5 · 2016: 2 · 2015: 5 · 2014: 4 · 2013: 5 · 2012: 7
- FWCI
- 4.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UO1AI-35839)
- National Institute of Allergy and Infectious Diseases (UO1 AI 35839, R01AI071160, U01AI043888, U01AI035839)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Keywords
- soluble TNF receptor 1, soluble TNF receptor 2, Plasmodium falciparum, placental malaria, malaria in pregnancy, asymptomatic malaria, parasitemia, biomarkers, low birth weight, syncytiotrophoblast, TNF-α
- MeSH terms
- Female, Humans, Infant, Low Birth Weight, Infant, Newborn, Malaria, Plasmodium falciparum, Predictive Value of Tests, Pregnancy, Prospective Studies, Cohort Studies, Biomarkers, Pregnancy Complications, Parasitic, Up-Regulation, Inflammation Mediators, Receptors, Tumor Necrosis Factor, Type I, Receptors, Tumor Necrosis Factor, Type II
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