Scientists have long known that when it comes to allergic reactions, the IgE antibody is the main culprit. But a groundbreaking new study has found the gut plays a powerful role in the process. Researchers at Stanford University say their findings could not only help determine the root cause of allergies, but also lead to life-changing treatments.
The California research team used an endoscope to take tissue samples from the esophagus, stomach and small intestine of 19 peanut-allergic people taking part in an oral immunotherapy trial. Then they closely examined those cells and compared them with ones found in the blood.
According to study lead author Ramona Hoh, PhD, they found that people’s rapid response to allergens is due in part to a “memory response” that’s contained in specific kinds of B cells in the gut. When those B cells encounter an antigen like peanut in a person with peanut allergy, they can switch into plasma cells and start pumping out reaction-inducing IgE antibodies.
“So this may be how these IgE antibodies get produced so quickly, because they’re actually residing in the stomach and duodenum tissue,” Hoh, a senior scientist in the department of pathology at Stanford University, told Allergic Living. She notes that the number of these IgE-producing cells was hundreds of times higher in the gut than what’s typically found in the bloodstream.
Using genetic analysis, the researchers were also able to confirm that the cells were being made in the stomach and the duodenum of the small intestine. This showed they were not being generated elsewhere in the body, and then traveling to the gut.
What’s more, many of the patients shared similar peanut-reactive IgE DNA sequences, which means their immune systems see peanut proteins in a similar way.
Other Food Allergens
“We think that’s extremely interesting because with antibodies you’re dealing with this hugely complex, diverse universe,” study co-author Dr. Scott Boyd told Allergic Living. “But if you look at enough people, you start to recognize the common patterns that are associated with the disease.”
“We think that may allow us to say who’s a better candidate for a certain kind of treatment, for example, or may allow us to better distinguish who is just sensitized to the allergen, but may not react strongly if they eat it,” said Boyd, the principal investigator at Stanford Medicine’s Scott Boyd Labratory for Human Immunology.
Titled “Origins and clonal convergence of gastrointestinal IgE+ B cells in human peanut allergy” the study was published in the journal Science Immunology. While it focused on peanut allergy specifically, Hoh and Boyd believe the process could be similar for other allergens.
“We set out to study peanut allergy because of its high incidence in the population,” says Boyd. “But in principal, we could have done the same study for tree nut allergy or shellfish allergy or others, and we suspect that we would have had similar findings, that there would be a lot of these IgE-expressing B cells in the gut.”
Hoh adds that the gut of a non-allergic person looks decidedly different. “That difference was most clear in the stomach – and the stomach isn’t really a tissue that’s known to have a lot of plasma cells or B cells of any type,” she says. “So it was a pretty dramatic finding.”
Cell Clues in the Tissue
IgE is the main catalyst behind allergic reactions. When people have allergies to peanuts or other substances, they develop IgE antibodies that recognize the proteins and other components of those specific allergens. The IgE then binds to the surface of mast cells. With exposure to the allergen, those cells then release inflammatory substances such as histamine. These set off reactions that can range from swollen eyes to hives or digestive symptoms and, in more serious cases, anaphylaxis.
In people without allergies, B cells are most often involved with helping to protect against infectious disease. For example, if you get a vaccination for measles or mumps, the B cells get stimulated by the vaccine and pump disease-fighting antibodies into your blood cells.
By analyzing the B cells that produce the allergen-specific IgE, the Stanford team hoped to help find the root cause of allergies. Until now, researchers have been almost entirely restricted to looking at the cells they can detect in the blood of patients, because getting samples of tissues in the gut is extremely challenging. Their efforts paid off.
“We know the human body is complicated, and a much bigger space than the blood alone. And there are certain tissues, like those in the digestive system where, if someone has food allergy, the reaction starts,” says Boyd. “And we had reason to suspect there may be a whole separate aspect of the immune system that’s localized to the tissues of the gut and the digestive system, and that those would be worth studying.”
Prospects for Treatment
Besides furthering the understanding of how allergic reactions work, Boyd and Hoh say the research could lead to better diagnosis, treatment and prevention. They raise the possibilty for treatments that could prevent the IgE antibodies from triggering reactions.
Boyd points to a recent study involving patients with cat allergies, in which participants were given a biologic drug that blocked the IgE response and significantly reduced the severity of their allergic reactions. “There’s no reason one couldn’t try to do the same thing for peanut allergy,” says Boyd. “It might be a bit more complicated because there are more allergen molecules involved, but it would seem like a viable thing to try.”
In recent years, scientists have developed a far greater understanding of the role the human microbiome plays in the allergic process, and Boyd says they’re starting to really hone in on potentially life-changing answers, which could lead to targeted treatments.
“My guess is there are going be more new treatments approved for allergy, and things that might be more suitable for one patient compared to another in the years ahead,” says Boyd. “So I think there’s room for guarded optimism in patients who suffer from these disorders.”
See the full study here.