Immunology of Pregnancy and Systemic Consequences

Menzies, Fiona M.; Henriquez, Fiona L.

doi:10.1007/978-3-319-16438-0_3

Cited by 1 publication

(1 citation statement)

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“…For example, uterine lymphocyte proliferation is suppressed during pregnancy in ruminants [12], while uterine natural killer cells that regulate blood pressure and flow to the placenta increase during pregnancy in mice [13]. In humans, pregnancy-induced hormonal changes lead to increased monocytes and granulocytes and decreased lymphocytes [14,15]. These pregnancy-associated immune changes also influence the progression of autoimmune diseases: 75% of females with rheumatoid arthritis who become pregnant show improvement of their symptoms, although these symptoms return three months postpartum [16,17].…”

Section: Introductionmentioning

confidence: 99%

Sex differences in immune function and disease risk are not easily explained by an evolutionary mismatch

Arner,

Muhoya,

Rozado

et al. 2024

Preprint

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The Pregnancy Compensation Hypothesis (PCH) posits that sex differences in the mammalian immune system reflect the effects of selection on female immunity during pregnancy, during which increased immunomodulation is required to reduce immune responses to the fetus, while maintaining the ability to respond to pathogens. In humans, fewer pathogens and lower parity in urban, industrialized environments has been suggested to leave female immune systems under-stimulated, creating an evolutionary mismatch which exacerbates sex differences in immunity and increases female autoimmune disease risk. Yet, robust tests of this mismatch hypothesis have not been conducted. Here, we first confirmed a sex-bias in autoimmune disease prevalence in a large dataset of individuals from the United Kingdom (UK Biobank). Second, we asked whether sex differences in immune function are affected by shifts toward urban, lower-parity lifestyles in a single population (the Turkana people of northwest Kenya). We found that lifestyle alters sex differences in immune cell type proportions, but not in gene expression levels. Contrary to expectations from the PCH, parity did not predict immune physiology. We then tested for generalizable trends across natural fertility mammalian populations versus urban humans (data from Turkana, NHANES, GTEx, Batwa and Bakiga, yellow baboons, and macaques). We did not find consistent relationships between lifestyle and sex-biases in immune biomarkers or between parity and the same immune outcomes. Indeed, we found that parity predicts autoimmune disease risk in the opposite direction than expected from the PCH, with higher parity associated with higher autoimmune disease risk while adjusting for relevant socioeconomic variables in the UK Biobank. Taken together, our work suggests that while sex clearly influences immune physiology and disease risk in urban settings, these effects are not easily explained by an evolutionary mismatch. Future work addressing how sex interacts with lifestyle change to generate disease is needed.

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