Descendants of Black Death survivors are more prone to autoimmune diseases – Liberation

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

Descendants of men who withstood the devastating bubonic plague pandemic 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, carried out by the University of Chicago scientist Jennifer Klunk, in collaboration with researchers from McMaster University (Canada) and the Institut Pasteur, published on 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 of the world at the time. At the origin of this hecatomb we find a disease-causing agent: the bacterium Yersinia pestis. “The plague bacillus is one of the most virulent infectious agents found on the face 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 triggered after infection by this bacterium in humans. For the researchers, a hypothesis is essential: the bubonic plague bacillus would have led to the selection of people with protective genes in the Middle Ages. “When a pandemic of this magnitude takes place, there is necessarily a selection in humans in favor of protective genes, which means that people susceptible to the circulating pathogen will die, explains 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

You still had to prove it. The researchers 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. Additional samples are taken from human remains at five burial sites in Denmark. By comparing DNA from victims and survivors of the Black Death pandemic, researchers identify key genetic differences that explain patients’ survival or death. Four selectable genes have been identified, all involved in the production of proteins that defend the body against pathogens. But certain versions of these genes, called alleles, provide protection against the Black Death. Thus, individuals living in middle age who carried two identical copies of a particular gene, called 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 in 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 researchers investigated the interaction between the bacterium Y. pestis and immune cells according to their Erap2 alleles, and analyzed how macrophages (cells with the ability to ingest and destroy large particles) neutralize the bacterium Y. pestis. “The results are categorical, continues Pasteur’s researcher. The “good” copies of the Erap2 gene enable more efficient neutralization of Y. pestis by immune cells. Having the correct version of Erap2 appears to have been essential for the immune cells to be able to destroy the Yersinia pestis bacterium.” 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, demonstrating the importance of the impact that a single pathogen can have on the development of the immune system.”

Disturbing conclusion

Because of this first result, the researchers undertook to identify the consequences of this genetic selection driven by the bubonic plague on the descendants of the survivors. Their conclusion is disturbing: the genes that once provided 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,” notes Javier Pizarro-Cerda. Evolution is definitely a double-edged sword.

Leave a Comment