Bubonic Plague and natural selection for autoimmune disease

Here is an interesting article suggesting that the Bubonic Plague, which killed maybe more than 30% of the population in Europe between 1346-1350, may have selected out genes that make the individuals more at risk for autoimmune diseases. Individuals who had these genes may have had a greater chance of survival; thus, the genes became more prevalent in the population.
 

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The team members identified four locations on the chromosomes where changes may have been driven by exposure to bubonic plague, including an increase in the frequency of the ERAP2 variant. They found that immune cells in people who carry this variant were more effectively able to kill Y. pestis, the bacterium that causes bubonic plaque, thus increasing the odds of surviving the disease by as much as 40 percent. But the ERAP2 variant has also been associated with a slight increase in the risk of developing Crohn’s disease, which is caused by inflammation of the digestive system.

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More broadly, our results highlight the contribution of natural selection to present-day susceptibility towards chronic inflammatory and autoimmune disease. We show that ERAP2 is transcriptionally responsive to stimulation with a large array of pathogens, supporting its key role in the regulation of immune responses. Therefore, selection imposed by Y. pestis on ERAP2 probably affects the immune response to other pathogens or disease traits. Consistent with this hypothesis, the selectively advantageous ERAP2 variant is also a known risk factor for Crohn’s disease, and ERAP2 variation has also been associated with other infectious diseases. Thus, selection for pathogen defence in the presence of pathogens such as Y. pestis may be counterbalanced against the costs of immune disorders, resulting in a long-term signature of balancing selection. Likewise, another of our top candidate loci (rs11571319 near CTLA4) is associated with an increased risk of rheumatoid arthritis and systemic lupus erythematosus, such that retaining the putatively advantageous allele during the Black Death confers increased risk for autoimmune disease in present-day populations

https://www.archaeology.org/news

https://www.nature.com/articles/s41586-022-05349-x