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Maternal body mass index is associated with an altered immunological profile at 28 weeks of gestation

April Rees Orcid Logo, Oliver Richards Orcid Logo, Anastasia Allen-Kormylo, Nick Jones Orcid Logo, Cathy Thornton Orcid Logo

Clinical and Experimental Immunology, Volume: 208, Issue: 1, Pages: 114 - 128

Swansea University Authors: April Rees Orcid Logo, Oliver Richards Orcid Logo, Nick Jones Orcid Logo, Cathy Thornton Orcid Logo

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DOI (Published version): 10.1093/cei/uxac023

Abstract

Healthy pregnancy is accompanied by various immunological and metabolic adaptations. Maternal obesity has been implicated in adverse pregnancy outcomes such as miscarriage, preeclampsia, and gestational diabetes mellitus (GDM), while posing a risk to the neonate. There is a lack of knowledge surroun...

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Published in: Clinical and Experimental Immunology
ISSN: 0009-9104 1365-2249
Published: Oxford University Press (OUP) 2022
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URI: https://cronfa.swan.ac.uk/Record/cronfa60423
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Abstract: Healthy pregnancy is accompanied by various immunological and metabolic adaptations. Maternal obesity has been implicated in adverse pregnancy outcomes such as miscarriage, preeclampsia, and gestational diabetes mellitus (GDM), while posing a risk to the neonate. There is a lack of knowledge surrounding obesity and the maternal immune system. The objective of this study was to consider if immunological changes in pregnancy are influenced by maternal obesity. Peripheral blood was collected from fasted GDM-negative pregnant women at 26–28 weeks of gestation. Analysis was done using immunoassay, flow cytometry, bioenergetics analysis, and cell culture. The plasma profile was significantly altered with increasing BMI, specifically leptin (r = 0.7635), MCP-1 (r = 0.3024), and IL-6 (r = 0.4985). Circulating leukocyte populations were also affected with changes in the relative abundance of intermediate monocytes (r = –0.2394), CD4:CD8 T-cell ratios (r = 0.2789), and NKT cells (r = –0.2842). Monocytes analysed in more detail revealed elevated CCR2 expression and decreased mitochondrial content with increased BMI. However, LPS-stimulated cytokine production and bioenergetic profile of PBMCs were not affected by maternal BMI. The Th profile skews towards Th17 with increasing BMI; Th2 (r = –0.3202) and Th9 (r = –0.3205) cells were diminished in maternal obesity, and CytoStim™-stimulation exacerbates IL-6 (r = 0.4166), IL-17A (r = 0.2753), IL-17F (r = 0.2973), and IL-22 (r = 0.2257) production with BMI, while decreasing IL-4 (r = –0.2806). Maternal obesity during pregnancy creates an inflammatory microenvironment. Successful pregnancy requires Th2-biased responses yet increasing maternal BMI favours a Th17 response that could be detrimental to pregnancy. Further research should investigate key populations of cells identified here to further understand the immunological challenges that beset pregnant women with obesity.
Item Description: The data underlying this article are available in the article and in its online supplementary material.
Keywords: obesity, pregnancy, immunometabolism, cytokines, Th subset
College: Faculty of Medicine, Health and Life Sciences
Funders: Diabetes UK
Issue: 1
Start Page: 114
End Page: 128