Clues to Solving Autoimmunity

Study of a potentially fatal food-triggered disease has uncovered a process that may contribute to many autoimmune disorders

Key Concepts

• Celiac disease (CD) is an autoimmune disorder triggered by ingestion of gluten, a major protein in wheat, or of related proteins in other grains.
• Research into the root causes indicates that the disorder develops when a person exposed to gluten also has a genetic susceptibility to CD and an unusually permeable intestinal wall.
• Surprisingly, essentially the same trio—an environmental trigger, a genetic susceptibility and a “leaky gut”—seems to underlie other autoimmune disorders as well. This finding raises the possibility that new treatments for CD may also ameliorate other conditions.

My vote for the most important scientific revolution of all time would trace back 10,000 years ago to the Middle East, when people first noticed that new plants arise from seeds falling to the ground from other plants—a realization that led to the birth of agriculture. Before that observation, the human race had based its diet on fruits, nuts, tubers and occasional meats. People had to move to where their food happened to be, putting them at the mercy of events and making long-term settlements impossible.

Once humans uncovered the secret of seeds, they quickly learned to domesticate crops, ultimately crossbreeding different grass plants to create such staple grains as wheat, rye and barley, which were nutritious, versatile, storable, and valuable for trade. For the first time, people were able to abandon the nomadic life and build cities. It is no coincidence that the first agricultural areas also became “cradles of civilization.”

This advancement, however, came at a dear price: the emergence of an illness now known as celiac disease (CD), which is triggered by ingesting a protein in wheat called gluten or eating similar proteins in rye and barley. Gluten and its relatives had previously been absent from the human diet. But once grains began fueling the growth of stable communities, the proteins undoubtedly began killing people (often children) whose bodies reacted abnormally to them. Eating such proteins repeatedly would have eventually rendered sensitive individuals unable to properly absorb nutrients from food. Victims would also have come to suffer from recurrent abdominal pain and diarrhea and to display the emaciated bodies and swollen bellies of starving people. Impaired nutrition and a spectrum of other complications would have made their lives relatively short and miserable.

If these deaths were noticed at the time, the cause would have been a mystery. Over the past 20 years, however, scientists have pieced together a detailed understanding of CD. They now know that it is an autoimmune disorder, in which the immune system attacks the body’s own tissues. And they know that the disease arises not only from exposure to gluten and its ilk but from a combination of factors, including predisposing genes and abnormalities in the structure of the small intestine.

What is more, CD provides an illuminating example of the way such a triad—an environmental trigger, susceptibility genes and a gut abnormality—may play a role in many autoimmune disorders. Research into CD has thus suggested new types of treatment not only for the disease itself but also for various other autoimmune conditions, such as type 1 diabetes, multiple sclerosis and rheumatoid arthritis.

Early Insights
After the advent of agriculture, thousands of years passed before instances of seemingly well-fed but undernourished children were documented. CD acquired a name in the first century A.D., when Aretaeus of Cappadocia, a Greek physician, reported the first scientific description, calling it koiliakos, after the Greek word for “abdomen,” koelia. British physician Samuel Gee is credited as the modern father of CD. In a 1887 lecture he described it as “a kind of chronic indigestion which is met with in persons of all ages, yet is especially apt to affect children between one and five years old.” He even correctly surmised that “errors in diet may perhaps be a cause.” As clever as Gee obviously was, the true nature of the disease escaped even him, as was clear from his dietary prescription: he suggested feeding these children thinly sliced bread, toasted on both sides.

Identification of gluten as the trigger occurred after World War II, when Dutch pediatrician Willem-Karel Dicke noticed that a war-related shortage of bread in the Netherlands led to a significant drop in the death rate among children affected by CD—from greater than 35 percent to essentially zero. He also reported that once wheat was again available after the conflict, the mortality rate soared to previous levels. Following up on Dicke’s observation, other scientists looked at the different components of wheat, discovering that the major protein in that grain, gluten, was the culprit. From the August 2009 Scientific American Magazine

By Alessio Fasano

From our home to yours, Tina Turbin
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