Notes on Engineering Health, July 2020: Why Are Some Foods More Allergenic Than Others?

The short answer to this seemingly simple question is: we don't know. The choreography of immune cells continues to be better understood, the reasons why we seem to be developing more allergies are being plumbed (from the hygiene hypothesis to the role of the microbiome), the way to treat symptoms are being advanced, but there is still a deep lack of understanding why some foods or common allergens are more prone to excite the immune system than others. Uncovering these differences will open the door to understanding the root causes of allergic reactions and engineer ways to modulate the immune response which is critical as the number of people worldwide with allergies is increasing.

The list of the most common food allergens is well known. Eight foods or food groups (peanuts, soybeans, cow's milk, eggs, fish, crustacean, wheat, and tree nuts) account for over 90% of food allergies. Why are there more allergic reactions to peanut than other legumes such as soybean or chickpeas?

A couple hypotheses could help explain the relative allergenicity of certain foods compared to others. One hypothesis revolves around the similarities of allergens to Metazoan parasite proteins. In a 2015 paper, a team lead by Nicholas Furnam from the London School of Hygiene & Tropical Medicine hypothesized that “there must be some molecular similarity between what the immune system is expecting and designed to see in parasites and what is present in the allergen proteins.” Driven by the fact that the same branch of the immune system thought to have evolved to combat multicellular parasite invasions like ticks and worms  kicks in when you have an allergic response, they were able to predict the immune reaction to a protein from the parasitic worm Schistosoma mansoni (SmBv1L) based on its similarity to a protein found in birch pollen from protein family BetV1, a prevalent pollen allergen.

A second, more recent discovery surrounds the variability and structural properties of allergens. Bernard Bihain and his team demonstrated that, in a subset of legumes at least, allergies do not develop because of canonical antigens but rather because of neo-antigens. These problematic neo-antigens are generated by “errors” made by RNA polymerase during protein expression. The more neo-antigens are produced (that is, the more mistakes that are made), the more allergenic the legume at hand. Peanuts it turns out are quite mistake prone, and thus are more allergenic than green beans (for example). The neo-antigens are the ones interacting with immune cells and provoking the development of antibodies against both the neo-antigens themselves and the canonical proteins. Being able to characterize peptides responsible for interacting with immune cells (they seem to be cationic, more basic, and with a higher isoelectric point) and provoke a response has profound implications in not only detecting dangerous foods but also engineering these peptides for vaccines as well as for desensitization purposes.

– Jonathan Friedlander, PhD & Geoffrey W. Smith