Why are millions of people allergic to peanuts or pollen, but hardly anyone seems to have a reaction to rice or raisins? Because only some of these things carry molecules similar to those found in parasites that send our immune systems into hyperdrive, according to a new study. The advance could help researchers predict what other foods might cause allergies.
Allergies begin when a type of antibody known as Immunoglobulin E (IgE) recognizes a so-called allergen—a peanut protein, for example—and binds to it. In some cases, this causes the immune system to overreact, ultimately leading to symptoms ranging from a runny nose to life-threatening anaphylactic shock.
Scientists have long argued that this mechanism originally evolved to defend humans and animals against parasites like certain worms. In developed countries, where people’s immune systems are hardly ever confronted by such parasites, the immune system may begin targeting other molecules by mistake, causing allergic reactions.
To bolster this hypothesis, a group of scientists led by computational biologist Nicholas Furnham at the London School of Hygiene & Tropical Medicine looked for similarities among 2712 proteins known to cause allergies and more than 70,000 proteins from 31 species of parasites. Using computer programs that compared the protein sequences as well as their 3D structures, the researchers identified a list of 2445 parasite proteins that are very similar to allergenic proteins. For instance, they found a protein in the worm Schistosoma mansoni that closely resembles one in birch pollen that makes people sneeze.
To see whether these predictions checked out in the real world, the scientists collected blood from 222 people in Uganda infected with the worm S. mansoni. They found that about one in six of them produced antibodies that recognized the pure worm protein. “We predicted that this protein in [S.] mansoni should be recognized by the immune system, because a fragment of it is similar to this birch protein which causes allergies,” Furnham says. It is “the first example of a plant pollen–like protein in a worm that is targeted by IgE,” the researchers write today in PLOS Computational Biology.
“It’s a very nice paper,” says Maria Yazdanbakhsh, a parasitologist at Leiden University Medical Center in the Netherlands. Some examples of allergens resembling worm proteins were already known, she says, but this is the first systematic look. “They present a method that allows you to identify new allergens. That’s a wonderful tool that can be applied to many things.”
One future use would be to screen new foods for possible allergens, Furnham says. The results could even help researchers design better therapies for people suffering from allergies, he argues. In immunotherapy (like allergy shots), people are exposed to increasing doses of an allergen to desensitize their immune systems. Knowing what parasite protein the allergen resembles could allow doctors to give that protein to patients instead of the pollen; that would make it easier to dose the allergy shots, as well as make the immunotherapy safer, Furnham says. “But that is a long way down the line,” he cautions.
A worm defense gone awry may explain some, but not all, allergies, says immunologist Ruslan Medzhitov of Yale University. He recently argued that some allergies may have an evolutionary purpose, like keeping humans away from environmental toxins. “Here the authors choose examples of allergens that support their view and ignore the ones that don’t,” he says. “This paper doesn’t change my opinion on the matter.”