It's been known that when the immune system encounters an allergen, it produces immunoglobulin E (IGe) antibodies. These antibodies bind to allergens and cause hives, shortness of breath, and anaphylaxis, symptoms that can result in death. These antibodies are the reason some people swell up from a whiff of peanut butter, while others gobble Skippy without a problem.
Now, a study published Thursday in Science points to the gut as the home of these allergy-causing antibodies, which offers insight into the mechanisms that drive their existence. The research was conducted on people with peanut allergies, but the findings could be game-changing for the estimated one in 10 adults with food allergies. Down the line, guided by this information, researchers may be able to hijack this production line and stop allergic reactions in their tracks.
What causes a severe allergy?
When allergic people ingest an offending substance — such as shrimp or dairy — the body deploys IGe antibodies, which set off an outsized immune response. Why some people produce IgE when encountering certain foods, while others eat the same things without triggering IgE, hasn't been totally clear.
Now, after scouring the tissue samples of 19 people with peanut allergies, scientists discovered a hotbed of IgE in the human gut. Previous research has traced IgE’s origin to the bone marrow, but this research suggests the gut may also be a “reservoir” of IgE antibodies, which drive severe allergies.
The research team discovered that certain cells in the gut — called B cells — act like factory workers. They typically produce harmless antibodies called immunoglobin G in response to food antigens, like peanuts. But at times, these factory workers mix it up: Instead of producing harmless antibodies, they start producing hyper-aggressive IgE antibodies, which cause severe immune reactions to things that may not be threatening.
This process is called class switch recombination (CSR). Figuring out a way to prevent or reverse this switch, could mean the end of severe allergic reactions, the study suggests. At this stage, scientists don’t know what environment or trigger sets off CSR, but according to the study, gut health could be involved.
The team also sequenced the DNA of the tissue, finding shared genetic patterns in the group. These commonalities suggest people with a peanut allergy might have a similar tendency to produce IgE in response to the nut.
How to stop an allergy attack
In the future, scientists might be able to stop this switch — preventing harmless antibodies from turning dangerous. Eventually, there may be a way to block IgE from binding with peanut proteins, avoiding all the uncomfortable and potentially lethal symptoms.
With other allergies, this approach has had some success. Two “defending” IgG antibodies were able to run interference in people with cat allergies, preventing IgE from binding to allergens. This defense strategy reduced allergy symptoms in mice and people, according to a 2018 clinical trial published in the journal Nature Communications.
If researchers can figure out how to harness certain antibodies to stop IgE, or prevent B cells from ever producing IgE antibodies in the first place, allergies could become a relic of the past — something that would have allergy-havers saying "bless you."
Abstract: B cells in human food allergy have been studied predominantly in the blood. Little is known about IgE+ B cells or plasma cells in tissues exposed to dietary antigens. We characterized IgE+ clones in blood, stomach, duodenum, and esophagus of 19 peanut-allergic patients, using high-throughput DNA sequencing. IgE+ cells in allergic patients are enriched in stomach and duodenum, and have a plasma cell phenotype. Clonally related IgE+ and non-IgE–expressing cell frequencies in tissues suggest local isotype switching, including transitions between IgA and IgE isotypes. Highly similar antibody sequences specific for peanut allergen Ara h 2 are shared between patients, indicating that common immunoglobulin genetic rearrangements may contribute to pathogenesis. These data define the gastrointestinal tract as a reservoir of IgE+ B lineage cells in food allergy.