The Black Death made people more susceptible to other diseases

By Gwyn Wright via SWNS

Surviving The Black Death came at a high price for modern Brits who are now more susceptible to diseases such as arthritis, multiple sclerosis and Crohn's, a new study has revealed.

Certain gene mutations made some people up to 40 percent more likely to survive the plague that last hit us in 1665.

But those mutations also made survivors more likely to get autoimmune diseases, where the body attacks itself.

Study co-author Dr. Tauras Vilgalys from the University of Chicago said: “I think studies like this help us understand why we're at risk for certain diseases, and how past pandemics have shaped current disease risks.

“Why does 50 percent of the population have these (ERAP2) variants that put you at increased risk for chronic disease?

“Part of the reason is that our genomes have been shaped by past infectious diseases, like The Black Death.

“Across the board, if we were to look at many risk alleles for modern disorders, you're probably going to see that those are protective against some disease that we've had in the past.”

For the study, researchers in the US, Canada and France collected DNA from people who had died shortly before, during and after The Black Death in London and Denmark.

The DNA was then sequenced and immune genes were examined across three time points to look for large changes in the frequency of the mutations over time.

They expected gene mutations that provided more protection from plague to be more common in people that died after The Black Death than before, and that mutations that confer susceptibility should cause the opposite pattern.

The team found four gene loci, which is the place on a chromosome occupied by a particular gene, matched this pattern.

These include mutations near ERAP2 and TICAM2.

ERAP2 is active in cells that eat and break down bacteria and viruses and give the immune system antigens so it knows how to fight diseases.

TICAM2 encodes an adapter protein for another protein called TLR4, which detects foreign bacteria in the body, such as plague.

The mutations were associated with differences in the expression of these two genes, which means the process by which genetic instructions are used to make gene products.

From this data, the team estimated that people with these mutations were 40 percent more likely to survive the plague.

To test how these variants performed against plague, monocytes- which are large white blood cells- were collected from the blood of living people with different ERAP2 and TICAM2 mutations.

These mutations had been exposed to different macrophages, which are types of white blood cell that engulf and digest pathogens, and they were then exposed to plague.

Macrophages with mutations that caused more ERAP2 to be expressed were more efficient at clearing plague than those without it.

The team says plague is “really sneaky” and immune cells only have a small window to detect and destroy it.

The findings suggest gene mutations near ERAP2 and TICAM2 may improve the detection of and resistance to plague, which likely protected people with these mutations during The Black Death and increased their chance of survival.

Mutations near ERAP2 and TICAM2 also help against other bugs, but not without a trade-off.

In particular, higher expression of ERAP2 is associated with autoimmune disorders in people today, including Crohn’s disease.

The study’s co-first author Jennifer Klunk from McMaster University in Ontario, Canada said: “It was exciting once we delved into to the variants (mutations), to see that our variants of interest show this signal of balancing selection.

“We were able to say one of the variants we're looking at clearly shows a signal of selective pressure over the course of Black Death, and we showed that it’s definitely involved in the immune response to yersinia pestis (plague), as well as other pathogens.

“But today that variant is also associated with a higher risk of autoimmune and inflammatory disorders.

“So being able to make that link was like, wow, that's something special.”

The team now wants to look at the whole genome, rather than just immune genes, to see if any other areas were affected by The Black Death or might have led to resistance, as well as the effects of demography and migration.

They also want to look at ERAP2 mutations in more detail to better understand how they help protect against the plague.

The findings were published in the journal Nature.