Q&A with Stephanie Eisenbarth, FARE Investigator in Food Allergy

Stephanie Eisenbarth, MD, PhD, is an associate professor of Laboratory Medicine, of Immunobiology and of Medicine (Immunology) at Yale School of Medicine. She received a 2017 Mid-Career FARE Investigator in Food Allergy Award for her research on a rare, inherited sensitivity to food allergens that could shed light on the mechanisms of food allergies in the wider population. Dr. Eisenbarth will be presenting an update on her work at the 2019 FARE Research Retreat, to be held April 13 in McLean, VA.

What first attracted you to food allergy research?

We have learned a tremendous amount about the immune pathways that drive allergic disorders such as asthma. Because food allergy, at the scale that it currently exists, is relatively new, our understanding of the fundamental immune processes that drive this form of allergy is still lacking. Similar to what has happened over the past two decades in the asthma field, I believe we can now develop a deeper understanding of how the immune system recognizes food allergens; this will advance our ability to accurately diagnose, treat and prevent food allergies.

What has sustained your interest?

The gut faces a daily challenge of protecting the body from pathogens and toxins while not mounting immune responses to non-pathogens and potential dietary allergens. As such, the immune system in the gut has to “decide” what is dangerous and what is harmless. Discovering how this process misfires to cause food allergy is the driving force behind our work. Ultimately, we aim to translate this understanding into new approaches to diagnose and treat food allergy.

What experimental finding has surprised you the most, and why?

We use mouse models of peanut allergy to study the immune response to food allergens. When we activate the immune system, we induce the expected production of peanut-specific IgE antibodies. IgE antibodies recognize allergens and can cause the massive inflammatory response of anaphylaxis. We were surprised, however, to find a balanced response by a potentially protective IgA antibody in the gut to the same food allergen. Yet IgA is not made to all foods; it requires specific immune triggers. Although the role of IgA in regulating the balance of bacteria in our gut has been recently well-studied, we know relatively little about this type of antibody immune reaction to food. Based on these surprising findings, we are trying to decipher the immunologic rules that govern when IgA is or is not made to a food allergen.

How might your FARE-supported research affect patient care in the future?

As a clinical pathologist, I work with allergists to help accurately diagnose allergy. Although a number of screening tests exist for sensing the immune response to allergens, these tests have limitations. For example, the presence in blood of IgE antibodies to an allergen indicates that the immune system has recognized and responded to that allergen; it does not always mean, however, that a person will have an allergic reaction to that allergen. Based on our ongoing work deciphering how the gut protects us from food-induced allergic reactions, we aim to develop new clinical assays that will help stratify patients based on likelihood to have an anaphylactic reaction to a particular food allergen.

What unresolved question relating to food allergies would you most like to see answered?

In order to develop new interventions, I believe we need to better understand the fundamental mechanisms of the immune response to food. Therefore, the two immunologic mysteries that I want solved in order to accomplish this goal are:

  1. How is IgE induced during the course of an immune response?
  2. What aspects of the immune response protects a patient from anaphylaxis in the face of a positive IgE test for an allergen?

We are working to answer these unresolved questions, but given their scope, tackling these questions will require a diverse and collaborative network of researchers.

Learn more about Eisenbarth’s research in this interview from last year’s Research Retreat.