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Out of balance: the role of evolutionary mismatches in the sex disparity in autoimmune disease

Keestra, SM; Male, V; Deniz Salali, G; (2021) Out of balance: the role of evolutionary mismatches in the sex disparity in autoimmune disease. Medical Hypotheses , 151 , Article 110558. 10.1016/j.mehy.2021.110558. Green open access

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Abstract

Over the past century autoimmune disease incidence has increased rapidly in (post-) industrialised, affluent societies, suggesting that changes in ecology and lifestyle are driving this development. Epidemiological studies show that (i) 80% of autoimmune disease patients are female, (ii) autoimmune diseases co-occur more often in women, and (iii) the incidence of some autoimmune diseases is increasing faster in women than in men. The female preponderance in autoimmunity is most pronounced between puberty and menopause, suggesting that diverging sex hormone levels during the reproductive years are implicated in autoimmune disease development. Using an evolutionary perspective, we build on the hypotheses that female immunity is cyclical in menstruating species and that natural selection shaped the female immune system to optimise the implantation and gestation of a semi-allogeneic foetus. We propose that cyclical immunomodulation and female immune tolerance mechanisms are currently out of balance because of a mismatch between the conditions under which they evolved and (post-)industrialised, affluent lifestyles. We suggest that current changes in autoimmune disease prevalence may be caused by increases in lifetime exposure to cyclical immunomodulation and ovarian hormone exposure, reduced immune challenges, increased reproductive lifespan, changed reproductive patterns, and enhanced positive energy balance associated with (post-)industrialised, affluent lifestyles. We discuss proximate mechanisms by which oestrogen and progesterone influence tolerance induction and immunomodulation, and review the effect of the menstrual cycle, pregnancy, and contraceptive use on autoimmune disease incidence and symptoms.

Type: Article
Title: Out of balance: the role of evolutionary mismatches in the sex disparity in autoimmune disease
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.mehy.2021.110558
Publisher version: https://doi.org/10.1016/j.mehy.2021.110558
Language: English
Additional information: © 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Evolutionary medicine; Cyclical immunomodulation; Autoimmune disease; Evolutionary mismatchImmune tolerance; Pregnancy compensation hypothesis
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL SLASH
UCL > Provost and Vice Provost Offices > UCL SLASH > Faculty of S&HS
UCL > Provost and Vice Provost Offices > UCL SLASH > Faculty of S&HS > Dept of Anthropology
URI: https://discovery.ucl.ac.uk/id/eprint/10127118
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