Crohn’s, tuberculosis, leprosy and... the plague!

As regards fundamental knowledge, the Nature study confirms an astonishing genetic link with certain relatively rare pathologies characterised by immunodeficiency. This is paradoxical, insofar as Crohn’s disease is caused by an excess of immunity rather than a lack of it. Perhaps the paradox is not what it seems. There could be two phases in the development of the pathology. First of all, an immunodeficiency of genetic origin leads to the poor management of the microbial environment, especially of the intestinal flora, which translates into an abnormal microbial colonisation in the first lines of defence. The typical inflammatory immune reaction of Crohn’s disease only occurs later, because the digestive system feels attacked. But the reaction is disproportionate; it causes more harm than good and destroys the digestive system.

The study also confirms a genetic link between Crohn’s disease and infectious diseases like tuberculosis, leprosy, and even... the plague! This link was already suggested in 2003 by a French researcher, Jean-Pierre Hugot, in a study published in the Lancet. The first gene associated with Crohn’s disease – Card 15 – is known for its role in immunity. And in the intestines of people with Crohn’s disease, we often find traces of bacteria from the Yersinia family (Yersinia Enterocolita, cousin of Yersinia Pestis, the bacteria responsible for the plague). Jean-Pierre Hugot’s hypothesis is as follows: in the Middle Ages, a certain number of people carried a particular form of the Card 15 gene which made them immune to the bacteria responsible for the plague. Petrus would carry this genetic mutation unlike all the other inhabitants in his village... Those, like Petrus, who survived the epidemics, had children and transmitted their genetic heritage to their descendents. Seven hundred years later, Pierre inherited this gene but as he now lives in Liège, he is no longer in contact with the plague bacterium (which is still rife but not on an epidemic scale in the world’s poorest regions, especially Africa). On the other hand, Pierre is often in contact with other bacteria from the Yersinia family (which colonise certain foods and are capable of resisting the cold temperatures of a fridge) but which are less dangerous than Pestis. And his immune system, which remembers the terrible epidemics of the Middle Ages, overestimates the dangers and reacts excessively. The inflammatory reaction in the intestine is disproportionate and turns against the sufferer.

This is how natural selection may have enabled certain people to escape epidemics that destroyed half of the population of Europe in the 14th century, but has now caused the pendulum to swing back in the form of one or more autoimmune diseases (Crohn’s, diabetes, etc.). And if we continue to follow the logic of natural selection, these new diseases are not likely to disappear, because they don’t prevent sufferers from having children and perpetuating their genetic heritage. Man has practically eradicated the plague. But he will perhaps have to live for a very long time with Crohn’s disease.