Could Mast Cell Disorders Be a Result of Humanity’s Past Battles with Infections like the Black Plague?

Plagues and pandemics are on the forefront of peoples’ minds today. And though the coronavirus may be the current plague of the hour, our histories are spotted with a litany of infectious assaults to which we’ve had to evolve over time.

The Black Plague was one such deadly culprit, which devastated the world’s Afro-Eurasian populations in the middle of the 14th century. Believed to have begun in Asia, it traveled into Crimea likely through the famous Silk Road and made inroads into Europe via Italy. From there it spread into mainland Europe, following trade routes as it spread across countries and over bodies of water.

Originally called The Great Mortality, it followed a few decades after the Great Famine and is believed to have killed half of the Eurasian population during its first wave. It is believed that poor living conditions precipitated by the Great Famine led to greater susceptibility to the Black Plague when it hit several decades later. Although its first wave was the deadliest, the Black Plague became a way of life off and on for hundreds of years, sometimes reemerging generation after generation.

Of course, the pressures for the immune system to adapt to the plague must have been intense. Interestingly, the 14th century physician to the Avignon Papacy, Raimundo Chalmel de Vinario, specifically noted

the falling virulence of the disease over time: in 1347 to 1348, it attacked about two-thirds of the populace and killed most; in 1360, it made about half sick and some survived; in 1375, about a 10th contracted it and many lived, while in 1382, only about five percent suffered and most survived [1].

There has been growing interest from chronic illness and clinical communities on the topic of mast cells and their related conditions. Mast cells are the major sentinels of the innate immune system, which are some of the first responders in most kinds of infections and provide signals that “rally the other troops.” When mast cells don’t work well or are suppressed (a method some bacteria use to evade the immune system), this can allow infections like the Black Plague to get a stronger foothold, making it harder for the immune system to fight back [2].

Because of this, it’s perhaps unsurprising that mast cells are vital players in fighting off Yersinia pestis (Black Plague) infection. For instance, scientists have found that when mast cells are suppressed using the mast cell stabilizer, cromolyn, Y. pestis is able to gain a stronger foothold in the organism, leading to worse infection and higher rates of death [3].

We don’t know for certain whether human mast cells have evolved to be more aggressive due to specific infections like the Black Plague, as this has not been studied directly. However, the role these sentinels play in Black Plague infection in the laboratory make them prime candidates for further study. Likewise, the virulence and high rates of mortality that accompanied the first bouts of the plague, as well as its rapid loss of virility over the following decades, indicate it was rapidly acting on the human genome and, specifically, the immune system.

It seems clear that a significant minority of the human population is plagued (pun intended) by unduly aggressive mast cells, suggesting this aggressiveness has undergone evolutionary selection– although conditions like mast cell activation syndrome may be the more extreme expressions of that tendency. But the prime candidates as drivers of that selection are past pandemics– most notably including the Black Plague, which is responsible for three of the five worst plagues in recorded human history [4].

Though mast cell disorders can be debilitating, who knows, they may in fact have been the very thing that kept our ancestors alive!

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