Severe Peanut Allergies Linked to Gut Reaction

A new study of 19 people who suffer from severe peanut allergies found an abundance of allergy-causing immunoglobulin E (IgE) antibodies in the gut, providing valuable insights into the mechanisms of severe allergies to peanuts and other foods, which together affect as much as six percent of the U.S. population.

peanut allergies

The study, published in Science Immunology and accompanied by a Perspective in Science, examined samples of IgE-producing B cells in gut tissue – very difficult to do – from participants beginning a clinical trial for peanut protein oral immunotherapy. The researchers found that antibody-producing B cells in the gut may switch production from harmless types of peanut-targeting antibody to IgE, through a process known as class switch recombination (CSR).

The results suggest that targeted prevention of CSR in the gut may be a promising treatment approach. What’s more, by defining and locating more IgE antibody types specific to other allergy-inducing foods, such as shellfish and tree nuts, the authors say, scientists could better track patient responses to treatments for these allergy types.

Reactions to food allergy vary widely, from mild inflammation to life-threatening anaphylaxis, depending on what kind of antibody binds to the food antigen. For example, when IgG binds to peanut proteins it is harmless, but binding by IgE can induce anaphylaxis. Few studies have examined IgE-producing B cells in tissues of patients with food allergy, in part because sampling these tissues is difficult and IgE is very short-lived.

peanut allergies

Here, exploring routine biopsies from 19 patients before they began peanut protein oral immunotherapy treatment, Ramona Hoh and colleagues sequenced antibody genes from B-lineage plasma cells in the stomach, duodenum and esophagus. They found that IgE-producing plasma cells were abundant in the stomach and duodenum. Many patients shared similar peanut-reactive IgE DNA sequences, suggesting that different individuals’ immune systems recognize peanut proteins in a similar manner. Hoh et al. also discovered multiple IgE-encoding sequences were shared by other antibodies in the same gut tissues – suggesting that the plasma cells in the gut environment undergo CSR to produce IgE.

In a related Science Perspective, Duane Wesemann and Cathryn Nagler argue that determining which features of the gut environment favor CSR to IgE – and what happens to IgE production in the gut after oral immunotherapy – should be high-priority questions for future studies.

NOTE: On March 26, 2020, Science will host a Facebook Live event focused on Hoh et al.’s work and on peanut allergy more broadly. The medical community and public public are welcome to attend the event (to be hosted on this page: https://www.facebook.com/ScienceMagazine) and to ask questions of the experts.