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.
Highlights
Over the past 150 years, life expectancy inindustrialised, affluent societies has increased concurrently with advances in public health, medicine, nutrition, and sanitation [1]
Less than 10% considers the sex of the participants in their analysis [151] and this bias persists in animal model studies [152]
Compared to other areas of biomedicine auto immune disease research has already acknowledged that taking sex and parity into consideration is key to understanding the female prepon derance in autoimmunity incidence, research on the proximate mecha nisms by which reproductive hormones influence tolerance mechanisms and autoimmune disease symptoms would benefit from an evolutionary medicine framework
Summary
Over the past 150 years, life expectancy in (post-)industrialised, affluent societies has increased concurrently with advances in public health, medicine, nutrition, and sanitation [1]. We propose that increased lifetime exposure to reproductive hor mones and number of menstrual cycles might alter central and pe ripheral tolerance mechanisms and contribute to an increase in autoimmune disease incidence in women living in (post-) industrialised, affluent contexts.
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