The Island of Autoimmunity

Nothing in biology makes sense except in the light of evolution.

On a windy spring day in Sardinia, I wander around a dilapidated bronze age tower built of black volcanic stone. I am accompanied by a neurologist by the name of Stefano Sotgiu. He tells of a mysterious structure towering above us-it is designated by the word nuraghe (“nurag”), where nur means” void “or” pile of stones ” in a language that was used before the Romans brought Latin to Sardinia. There are more than seven thousand such structures on the island, whose age at the time of the arrival of the Romans more than two thousand years ago was 1500 years. The nuragas serve as an important cultural reference point: while the Christian world begins its chronology with the birth of Jesus, the Sardinians, according to Sotgiu, divide history into before and after the appearance of the nuragas — “our era” for them lasts for almost 2000 years more.

No one knows why the nuraghs were built, although there is speculation that these towers provided people with shelter from mosquitoes. And this blood-eating insect had a great influence on the mentality of the inhabitants of Sardinia. In Cagliari (the main city of the island, located in the southern part of it), the local virgin Mary is called “our mother of God Bonaria”. The word bonaria means “good air”, is an antonym of the word malaria, which comes from the Latin word for “bad air”. However, in modern times, archaeologists tend to describe these towers as status symbols created in bronze age versions of modern skyscrapers.

That we have with Sotgiu Nuraghe are ready-made metaphor for conversation. For some inexplicable reason, Sardinia has the highest prevalence of autoimmune diseases in the world, which is why I came to the island. Sardinians are two to three times more likely to develop multiple sclerosis than Italians living on the mainland, or those living on nearby Islands such as Corsica in the South or Sicily in the Southeast. And on such an indicator as the susceptibility to autoimmune diabetes (type 1 diabetes), Sardinians are second only to Finns.


An alternative explanation puts this down to genes, which is probably generally correct. However, Sotgiu developed this hypothesis further than usual. He posed the question: what can these “autoimmune” gene variants be intended for (what is their purpose) and why are they so common among Sardinians?

Stefano Sotgiu did not have to delve into the distant past in search of an answer. Malaria was widespread on the island 60 years ago. Parents, uncles and aunts of Sotgiu suffered malaria, as well as their parents and grandparents. Until the mid-twentieth century, malaria fever was a kind of rite of passage on the island — and this situation persisted for thousands of years. People who were resistant to these parasites survived; those who were not so resistant died. The inhabitants of Sardinia began to increase the number of gene variants that provide protection against malaria. Like the mysterious Nuraghi that characterize the island’s landscape, these protective genes now define the Sardinian genome. According to Sotjiu, these gene variants increase the likelihood of developing autoimmune diseases. Predisposition to multiple sclerosis is the price paid by the inhabitants of the island for excellent antimalarial protection.

I follow Sotgiu the spiral staircase of rough-hewn stone. We go to the platform, located at an altitude of almost 20 meters, which offers a panoramic view. Before us stretches a windswept grassy plain, surrounded in the distance by gentle hills. Trenches dug by order of Benito Mussolini in the thirties cross the meadow below. These trenches were to drain the malarial swamps once and for all. Conical huts with thatched roofs (a design common in old Europe) rise here and there from the tall grass. Sotjiu says that these huts are used mostly for keeping sheep these days, but once people lived there. Birds soar at eye level-they are supported by the North-West wind, which in Sardinia and mainland Italy has its own name: il vento maestrale (“Mistral wind”).

As we survey the plain, Stefano, carefully pronouncing English words, lists the extreme factors that determine life in his homeland. The number of sheep on the island exceeds the population by almost two times. This island is the least populated area in Europe. Sardinia has the lowest birth rate in Italy and one of the lowest in Europe. The island has a high unemployment rate. Members of the younger generation often leave the island to join the Sardinian Diaspora in Spain or mainland Italy, as well as elsewhere. In addition, Sardinia is home to the most centenarians — people who have reached the age of 100 years.

Sotgiu explains that outsiders have long considered Sardinia a backwater, an island of rough peasants and shepherds who prefer a secluded lifestyle. (I later learned that in the Italian version of the American Simpsons cartoon, gardener Willie, who is considered a Scot in the United States, had a Sardinian accent.) However, distrust is mutual. “We are very suspicious of outsiders,” says Sotgiu. For three thousand years, potential rulers came to the island from the sea. In response, the Sardinians went deep into the island. “In all probability, this is why we were not changed by all these conquests,” says Sotgiu. This isolation (both literally and figuratively) partly explains the uniqueness of the Sardinian genome and its vulnerability to autoimmune diseases.

Today, one in 430 Sardinians suffers from multiple sclerosis — a degenerative disease of the Central nervous system that causes people to lose the ability to move their limbs, see, and eventually breathe [94]. (This is official data, but Sotgiu told me in confidence that according to unpublished data, this figure is even higher.) One of the 270 Sardinians has type 1 diabetes — an autoimmune disease in which the immune system attacks the insulin — producing organ, the pancreas.

The statistics were not always the same here. In Sardinia, there is a certain “zero year” of autoimmune diseases. Immune-mediated diseases began to spread rapidly after the eradication of malaria in the 50s. Sotgiu believes that such a time frame is not accidental. It is possible that malaria provided natural selection in favor of genes with a predisposition to autoimmune diseases. However, the infectious disease that causes malaria Plasmodium (Plasmodium falciparum), most likely, protected a person from the dark side of the very genes that it contributed to the formation of. In this respect, Sotgiu’s hypothesis differs from the more trivial judgments of geneticists. He believes that the highly specialized immune system of Sardinians functions properly only in the presence of an infectious agent, for which it was prepared by evolution. Essentially, the Sardinians need to interact with their old enemy to escape the demons hiding inside.

Leave a Reply

Your email address will not be published. Required fields are marked *