Have An Autoimmune Disease? Blame The Black Death

Can you guess why?

From the strong came forth weakness

First, a quick history refresher: the Black Death was a devastating outbreak of bubonic plague caused by the bacterium Yersinia pestis.

This happened in the mid-1300s, and killed 25–50 million people across Europe.

From a modern perspective, it’s clear to see that that’s a lot of people, but to truly understand how much of a natural selection event this was, bear in mind that in the early 1300s, the world population had not yet expanded to anywhere near what it has today, and thus:

• Now: that’d be more than 3% of the people in Europe
• Then: that was up to 50% of the people in Europe

So, as we say, quite a natural selection event, to say the least.

A study (cited in the video) analyzed DNA from several hundred people buried before, during, and after the Black Death in London and Denmark. The researchers compared immune-related genes to identify variants that became more common among survivors. In particular, out of about 20,000 human genes, the study examined about 400 genes involved in immune function, looking for variants that increased in frequency after the plague.

Of these, one of the strongest signals involved the ERAP2 gene, which helps train immune cells, clear pathogens, and regulate inflammation. Of those, one version (type A) produces a full-length, functional ERAP2 protein, while another (type B) produces a shortened protein that is quickly broken down by cells.

There are consequences to combinations:

• Survival advantage: people with two copies of the type A ERAP2 variant were estimated to have been about 40% more likely to survive the Black Death because the variant likely improved recognition of plague bacteria while helping control inflammation.
• Evolutionary downside: the same ERAP2 variant associated with plague survival is also linked to an increased risk of Crohn’s disease, and a stronger immune system can become overly aggressive.

There are also other immune tradeoffs: another genetic region identified as protective against the plague has been linked to other autoimmune diseases such as lupus and rheumatoid arthritis.

So, if you have an autoimmune disease that you got due to genetic risk factors, it’s nice to remember that without them, your would-be ancestral line would more likely have ended in the 1300s.

For more on all of this, enjoy:

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Want to learn more?

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Take care!