Having grown up with allergies, I am very familiar with the painstaking process of skin and blood tests used to determine my sensitivities to a variety of pollen types. From my experiences, I have realized that the most interesting part of allergies is the unpredictability. When I shadowed Dr. Grace Koo at the Vanderbilt Asthma, Sinus & Allergy Program last fall, I learned more about how impossible it was to guess how someone’s allergy is going to progress. A person who has eaten soy their entire life can suddenly break into hives the next time that they eat tofu. As I watched this physician recommend patients treatments, I quickly understood that this area of medicine is not about curative treatment, but rather about management.
Enter the peanut allergy. About two percent of Americans have a peanut allergy, which usually develops in childhood and persists into adulthood. It is also characterized as having more severe reactions than other food allergies. One of the more recognizable reactions is anaphylaxis, a life-threatening response characterized by hives, difficulty breathing, and shock. While an EpiPen is the go-to solution for this issue, it requires the person to always have it on hand.
An alternate solution is to disrupt the interactions that cause an allergic reaction. When an allergen enters the body, the immune system identifies them as antigens even though they are harmless. Antigens are foreign substances that cause potential harm to the body, and even though allergens do not cause harm, the immune system still reacts and mounts a response as though they are harmful. This triggers the production of immunoglobulin E (IgE) antibodies, which then bind to cells that cause an allergic reaction.
Because not much is understood about the IgE antibodies generated due to peanut allergens, the first step is to identify how these antibodies bind. At Vanderbilt, the labs of Dr. Scott A. Smith and Dr. Benjamin A. Spiller are looking at the structure of peanut allergens and how they interact with IgE antibodies. Initially, they needed to determine what regions in peanut allergens trigger anaphylaxis. Blood samples were taken from 15 patients at the Vanderbilt University Medical Center who had severe peanut allergies. Hybridomas, cells that generate antibodies, were created from these samples. Because hybridomas create IgE antibodies from real patients, the labs can study the structure of antibodies that are produced in response to peanut allergens. After characterizing these antibodies, the labs found that these 63% of antibodies bind specifically to two kinds of peanut allergens: Ara h 2 and Ara h 6. When both antibodies were injected into mice, they caused anaphylaxis, and when only Ara h 6 was injected, it induced the response by itself.
Next, the Smith and Spiller Labs investigated how the Ara h 2 and Ara h 6 allergens interact with antibodies. Because they are the most common allergens to cause anaphylaxis due to peanuts, their antibodies are the first molecular targets for hypoallergen treatment. Between the two allergens, two sites were found to be highly conserved that bind to the IgE antibody similarly.Usually, antigens bind to specific antibodies, but structural similarities allow for cross-reactivity, resulting in two antigens being able to bind to the same antibody. By studying the biochemical reactions between antigen and antibody, further research can investigate how to prevent anaphylaxis. Considering the recent growth in the field of allergy medicine, this study could eventually lead to the development of a vaccine that works similarly to other allergy shots. These vaccines introduce a mutated version of the allergens that produces smaller immune responses, which allows the immune system to accommodate allergens. This preventative approach towards the peanut allergy could make it easier for patients to manage their health.
Could this be the end of the peanut allergy? It is definitely a start, but in general, research into anaphylactic reactions and allergy-related deaths has the potential to be life-changing for a large population.
References
Lieberman, J. A., Gupta, R. S., Knibb, R. C., Haselkorn, T., Tilles, S., Mack, D. P., & Pouessel, G. (2021). The global burden of illness of peanut allergy: A comprehensive literature review. Allergy, 76(5), 1367–1384. https://doi.org/10.1111/all.14666
Smith, S. A., Khan, Y. W., Shrem, R. A., Hemler, J. A., Doyle, J. E., Daniel, J., Zhang, J., Pena-Amelunxen, G., Aglas, L., Hamilton, R. G., Getts, R., Sampson, H. A., Wong, J. J. W., Croote, D., Peebles, R. S., & Spiller, B. W. (2025). Antigenic determinants underlying IgE-mediated anaphylaxis to peanut. Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2024.12.1094
Smith, S. A., Shrem, R. A., Lança, B. B. C., Zhang, J., Wong, J. J. W., Croote, D., Peebles, R. S., & Spiller, B. W. (2025). Structural determinants of peanut-induced anaphylaxis. Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2024.12.1095
