Survivors of descendants of the Black Death at increased risk of autoimmune disease

Survivors of descendants of the Black Death at increased risk of autoimmune disease

In a study published Wednesday in the journal Nature, researchers show that genes that protect individuals from a deadly medieval epidemic now increase the risk of declaring Crohn’s disease or rheumatoid arthritis.

The descendants of the men who resisted the devastating bubonic plague that swept Europe, Asia and Africa nearly seven hundred years ago are today at increased risk of developing autoimmune diseases. This is the conclusion of an exciting research on genetic predispositions, conducted by University of Chicago scientist Jennifer Klink, jointly with researchers from McMaster University (Canada) and the Pasteur Institute, published on Wednesday in the international journal temper nature.

The Black Death epidemic that broke out in the Middle Ages remains the deadliest event in the entire history of mankind, responsible for the death of 30% to 50% of the population in some of the most densely populated areas of the world at the time. At the origin of this hepatomegaly, we find a pathogen: the bacterium Yersinia pestis. “The plague bacillus is one of the deadliest infectious agents found on Earth, comments Javier Pizarro-Cerda, co-author of the study, director of the Yersinia Research Unit at the Institut Pasteur. We have been interested in the molecular mechanisms of pathogenesis of this microorganism, as well as the immune responses that are triggered after infection with this bacterium in humans. For researchers, the hypothesis is necessary: ​​the bubonic plague bacillus in the Middle Ages led to the selection of humans with protective genes.. “When a pandemic of this magnitude occurs, there is necessarily a selection in humans in favor of protective genes, which means that people who are exposed to infection with circulating pathogens will die, Explains biologist and evolutionary geneticist Hendrik Poinar, who is also a study co-author. 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 gene Erap2

It still has to be proven. So the scientists analyzed ancient DNA samples extracted from the remains of individuals who died before, during or after the Black Death in London, where there are many well-preserved and well-dated graves. Other samples of human remains were taken at five burial sites in Denmark. By comparing the DNA of victims and survivors of the Black Death pandemic, researchers identify key genetic differences that explain the survival or death of patients. Four selectable genes have been identified, all of which are involved in the production of proteins that defend the body against pathogens. However, certain versions of these genes, called alleles, confer protection against the Black Death. Thus, medieval individuals carrying two identical copies of a particular gene, called Erap2, had a 40% to 50% higher survival rate than those with different alleles. “There are few teams in the world able to study the interactions between cells of the immune system and Y. pestis bacteria. Our experience has made it possible to demonstrate the true impact of an Erap2-related phenotype on the response to live plague bacteria,” Christian Demeur, researcher in the Yersinia unit at the Pasteur Institute explains.

Using human cells, the scientists studied the interaction between Y. pestis bacteria and immune cells according to their Erap2 alleles, and analyzed how macrophages (cells that have the property to engulf and destroy large molecules) neutralize Y. pestis bacteria. “The results are conclusive, Researcher Pasteur continues. ‘Good’ copies of the Erap2 gene allow for more efficient inactivation of Y. pestis by immune cells. It appears that getting the correct version of Erap2 was critical for immune cells to be able to destroy Yersinia pestis. ” Geneticist Luis Barreiro, co-author of the study and professor of genetic medicine at the University of Chicago, echoes the following: The selective feature associated with location [position d’un gène sur un chromosome, ndlr] Selection is one of the most powerful agents ever reported in humans, illustrating the importance of the impact that a single pathogen can have on the development of the immune system.”

disturbing conclusion

Building on the strength of this first finding, scientists have pledged to determine the consequences of this genetic selection by bubonic plague on the offspring of survivors. Their conclusion is alarming: Those genes that once provided protection from the Black Death are now linked to increased susceptibility to autoimmune diseases, such as Crohn’s disease and rheumatoid arthritis. “The identification of Erap2 reinforces the idea that what allows for survival in one era can alter survival in another,” Notes Javier Pizarro Cerda. Evolution is definitely a double-edged sword.

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