The Black Death and the Modern Link to Autoimmune Diseases

Drain C.

Genetics, Stockton University

https://www.bbc.com/news/health-63316538 

During the 1300s, the deadliest plague was raging across Europe, killing approximately 200 million people in its path. Medicine was merely a thought and there was really no true way of fighting off this deadly disease. But somehow people managed to survive. For those who have managed to survive the plague, studies have found a mutation on the endoplasmic reticulum aminopeptidase 2 gene.  Not saying that everyone who had this mutation survived, but those who had the mutation were 40% more likely to survive. That's great! 

But, in modern day health and science studies have found that same exact gene mutation is causing an increase in autoimmune diseases such as Crohn's disease. The same mutation that basically eliminated the deadliest plague, is now the cause of other silent diseases. While causing an overabundance in the enzymes that destroy the unhealthy cells, the enzymes attack the healthy cells too. ERAP2 does not have an off function, so it will continue to produce enzymes that negatively affect the body. Treatments for specific auto immune diseases include an increase of ERAP2 inhibitors. 

 

Auto-immune diseases are often categorized as the infected immune cells targeting and attacking the healthy cells or organs. Initially auto immune diseases were thought to be inked to stress, but with recent studies there have been additional linkages to genetics and an outside surrounding environment. Your body is supposed to remove the infected cells, but to an auto-immune disease there is no differentiation of what a healthy cell and an unhealthy cell looks like. Unfortunately, everything is caught in the cross-fire and every cell is attacked. This article is saying that although genes are a factor to an auto-immune disease, that is not the final be all. There can be people in your family that do not have the linked gene but you could, or vise versa. Having an auto-immune disease may not be entirely inheritable. Scientists and researchers are still looking into the causes and effects of autoimmune diseases.  

https://www.hopkinsmedicine.org/health/wellness-and-prevention/autoimmune-disease-why-is-my-immune-system-attacking-itself

Black Death Genes and Increasing Autoimmune Disorders

FOOD FOR THOUGHT:

 Genes that once protected our bodies during the Black Death, may now be increasing autoimmune disorders...

    An article from Harvard Medical School (HMS) details how genes that once protected our bodies during the Black Death in the 14th century, may now be increasing the prevalence of autoimmune diseases. Researchers have extracted the DNA of people who died during the time of the Black Death, and are using that to compare against the DNA of those who have lived through the COVID-19 pandemic (our time). From this data, they were able to deduce the fact that survivors of each pandemic carried genes that made them immune to the disease. This makes sense, considering the "survival of the fittest" philosophy introduced by Darwin, and due to evolutionary circumstances, it would make sense that those who survived one instance of a deadly disease could presumably survive another. The bacterium Yersinia pestis was known to cause the Black Death as it spread from animals to humans, and plays a role now, centuries later. The relevance comes into play with autoimmune disorders: those alive during our time with autoimmune diseases are more likely to carry those same infection-fighting genes that helped people survive the Black Death -- crazy right?

    This was a very fascinating article and it is interesting to see how the genes have been passed on evolutionarily through time. Not only that, but the human body has me awestruck. The things that it is capable of, such as passing on these genes that can prevent disease is so interesting to me. Furthermore, as someone with an autoimmune disease, I can't help but to wonder if I carry these same genes as well. I think it would be really fascinating to have my DNA extracted and compared to that of someone who survived the time of the Black Death, that way I could truly see if I am impacted by this phenomena. Selective pressures and immunity are quite interesting to me and I could see myself taking a deeper look into this topic in the future!

LINKS:

1. https://www.health.harvard.edu/blog/genes-protective-during-the-black-death-may-now-be-increasing-autoimmune-disorders-202212012859 

2. https://www.nature.com/articles/s41586-022-05349-x

Genes that may help you survive the Black plague, but not your own immune system

An article by Science discusses research that suggests certain genes helpful in surviving the Black Plague centuries ago may be increasing the risk for modern autoimmune diseases. This research was led by Mihai Netea in Romania. Netea compared genomes of ethnic groups that survived the Black Plague and those that did not experience it. They were able to pinpoint genes on chromosome 4 that are critical to the immune system. These genes found in the survivors code for proteins with receptors that are very responsive to the Black Plague bacterium, Yersinia pestis. As a group, those who did not experience the Black Plague often lacked these genes. It was hypothesized that these contributed to an over active immune system that was vital in surviving a deadly pandemic. 

However, this immune system is not as helpful today. These receptors have started triggering immune responses to an individual's own body and leading to long term autoimmune disorders. Today, those who have the genes found in Black Plague survivors are often at a higher risk to develop Crohn's disease, rheumatoid arthritis, lupus, and other autoimmune diseases. This research demonstrates the fascinating effects that passing on genes can have over generations. It also brings up the idea that the traits which are positively selected for are very dependent on the time and environment in which they exist.

Not All Identical Twins Have Identical Geneotypes

 

    Iceland researchers recruited 381 sets of identical twins and found that only 38 pairs possessed the same exact genes. On the other hand, most of the twins had many genetic differences and 39 pairs of twins had more than 100 differences in their genes. On average the pairs of twins differed by approximately 5.2 gene mutations. These differences were likely determined before birth, before, or just after one embryo split to become two. Many mutations arise because the enzyme tasked with copying our DNA makes mistakes, and if the mistakes are not corrected, it results in gene variability among the pair. Mutations discovered in the newly studied twins infer that embryos do not split in half neatly when the two twins are formed. Hence, the more uneven the split of the embryo, the greater the gene difference will be between the twins. 

    Some of these mutations, likely given to one of the twins only, can be bold and hapless. In nearly three-quarters of cases of monozygotic twins having an autoimmune disease, only one twin is affected. This is called, “disease discordance,” and includes conditions like hemophilia, multiple sclerosis, and Duchenne muscular dystrophy. Rarely, some "identical" twins may even end up with differing sex chromosomes. Monozygotic twins, as they should be called, may appear identical at first glance, however, very complex dynamics are at play under the surface. 

Helpful Links:

Article: Some identical twins don’t have the exact same DNA

Article: Identical Twins Are Not Identical

By Katherine Morone