Descendants of Black Death survivors more at risk of autoimmune diseases – Liberation

In a study published this Wednesday in “Nature”, researchers show that genes that protected individuals from the deadly pandemic in the Middle Ages now increase the risk of declaring Crohn’s disease or rheumatoid arthritis.

The descendants of men who withstood the devastating pandemic of bubonic plague that swept across Europe, Asia and Africa nearly seven hundred years ago today are at increased risk of developing an autoimmune disease. This is the conclusion of an exciting research on genetic predispositions, conducted by University of Chicago scientist Jennifer Klunk, in association with researchers from McMaster University (Canada) and the Institut Pasteur, published this Wednesday. in the international journal Nature.

The Black Death epidemic that raged in the Middle Ages remains the deadliest event in all of human history, responsible for the death of 30% to 50% of the population in some of the most densely populated regions. in the world at the time. At the origin of this hecatomb, we find a pathogenic agent: the bacterium Yersinia pestis. “The plague bacillus is one of the most virulent infectious agents that exists on the surface of the Earth, comments Javier Pizarro-Cerda, co-author of the study, director of the Yersinia research unit at the Institut Pasteur. We were interested in the molecular mechanisms of pathogenicity of this microorganism, as well as the immune responses that are triggered after infection by this bacterium in humans. For the researchers, a hypothesis is essential: the bacillus of the bubonic plague would have in the Middle Ages led to the selection of human beings holders of protective genes. “When a pandemic of this magnitude takes place, there is necessarily a selection in humans in favor of protective genes, which implies that people susceptible to the circulating pathogen will die, explains the biologist specializing in evolutionary genetics Hendrik Poinar, also co-author of the study. The slightest selective advantage will make the difference between survival or death. Of course, survivors of childbearing age will pass on their genes.”

The importance of the Erap2 gene

Still had to prove it. The scientists therefore analyzed ancient DNA samples extracted from the remains of individuals who died before, during or after the Black Death in London, where there are several particularly well-preserved and well-dated cemeteries. Further samples are taken from human remains at five burial sites in Denmark. By comparing the DNA of victims and survivors of the Black Death pandemic, researchers identify key genetic differences explaining the survival or death of patients. Four selectable genes are identified, all involved in the production of proteins that defend the body against pathogens. However, certain versions of these genes, called alleles, do confer protection against the Black Death. Thus, individuals living in the Middle Ages carrying two identical copies of a particular gene, named Erap2, had a 40% to 50% higher survival rate than those with different alleles. “Few teams in the world are able to study the interactions between cells of the immune system and the bacterium Y. pestis. Our expertise has made it possible to show the real effect of the Erap2-related phenotype on the response to a live plague bacterium,” explains Christian Demeure, researcher in the Yersinia unit at the Institut Pasteur.

Using human cells, the scientists studied the interaction between the bacterium Y. pestis and immune cells according to their Erap2 alleles, and analyzed how macrophages (cells with the property of ingesting and destroying large particles ) neutralize the bacterium Y. pestis. “The results are categorical, continues Pasteur’s researcher. The “good” copies of the Erap2 gene allow more efficient neutralization of Y. pestis by immune cells. Having the correct version of Erap2 appears to have been critical for the immune cells to be able to destroy the Yersinia pestis bacteria.” Geneticist Luis Barreiro, study co-author and professor of genetic medicine at the University of Chicago, echoes this: “The selective advantage associated with loci [position d’un gène sur un chromosome, ndlr] selected is one of the most potent ever reported in humans, which demonstrates the importance of the impact that a single pathogen can have on the evolution of the immune system.”

Disturbing conclusion

On the strength of this first result, the scientists undertook to identify the consequences of this genetic selection operated by the bubonic plague on the posterity of the survivors. Their conclusion is disturbing: those genes that once conferred protection against the Black Death are now associated with an increased susceptibility to autoimmune diseases, such as Crohn’s disease and rheumatoid arthritis. “The identification of Erap2 reinforces the idea that what allows survival in one era can alter survival in another era”, notes Javier Pizarro-Cerda. Evolution is definitely a double-edged sword.

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