Funding better "biomarkers" for food allergies

Update 5/1/15: Congratulations on surpassing the $50,000 funding goal before the April 30th deadline! Here are two wonderful summaries of the effort: Caroline Moassessi of Grateful Foodie and Henry Ehrlich at Asthma Allergies Children weigh in.

When our food allergy journey started out, one of the most challenging things to wrap my head around was allergy testing. I distinctly remember looking incredulously at our allergist and thinking, “You mean to tell me that a “positive” blood test or that giant hive from a skin prick test doesn’t necessarily mean our son has a REAL food allergy? What good is that?!”

Two common allergy tests rely on the IgE antibody as a "biomarker." The tips of the IgE antibody recognize specific food proteins, such as those found in a peanut. Blood tests measure the amount of IgE for a specific food that is found in the blood and skin prick tests look for the result of a food protein binding to IgE attached to a mast cell in the skin. The release of histamine (among other chemicals) causes the wheal or hive in a skin prick test. Image source: Atlas of Allergic Diseases

What I have learned over the course of several years is that there really are no great tests for food allergies – i.e. “biomarkers” –aside from actually consuming the food (oral food challenge supervised by a clinician). The two common current methods of testing - blood tests measuring food-specific blood IgE levels and skin prick tests that scratch the allergen into the skin surface are not a great tests because they frequently give “false positive” results. A “false positive” means that a person may test “positive,” but truly isn’t positive should they actually consume the suspected food. Frustrating. On top of this, most current testing methods that rely on IgE as a “biomarker” cannot predict how severe the allergy is. The only sure way to test for a suspected food allergy is to go to your allergist’s office and perform the supervised oral food challenge – you know, the test where you actually eat the suspected allergen and wait for a response. Having done this with my son several times now, I can’t stress enough just how stressful this stressful test is. There has to be a better “biomarker” – a test without the stress and risk of a reaction that can better predict an allergy and its severity. 

Image source: Selena Bluntzer from Amazing and Atopic

To help solve this problem, Dr. Xiu-Min Li, Professor of Pediatric Allergy and Immunology at the Icahn School of Medicine at Mount Sinai, and board-certified allergists Dr. Paul Ehrlich and Dr. Purvi Parikh designed a collaborative, practice-based study whose primary objective is to figure out better biomarkers of allergy (details of the study and how you can directly fund the study).

Can we establish safe allergen thresholds in foods? What does the current science say?

In light of the open request from the US Food and Drug Administration (FDA) seeking public feedback on whether food manufacturers can set a “safe” threshold for major food allergens (peanut, milk, egg, etc.), I wanted to reason through this question with the existing scientific evidence regarding food allergy.

Egg-cellent news

Thursday was a stressful day to say the least. It was food challenge day, and it marks the first time in living with food allergies that hope may indeed be reality.

So, when does this egg story begin?  December of 2009 marks the last time that JR, our handsome young 1 year old at the time, ate anything with eggs.  Before that point, JR regularly devoured scrambled eggs.  Like any parent, I enjoyed watching my growing boy enjoy such a wonderful source of protein.  But in December 2009, the immune "switch" was flipped and our joy quickly turned to terror as scrambled eggs suddenly evoked the scariest of immune system responses, anaphylaxis.  Vomiting, lip swelling, hives, coughing - all within 5-10 minutes.  The incredible, edible egg suddenly became not-so-incredible and definitely not edible.  For JR, eggs were poison.  (As a side note, a few weeks after the scrambled egg incident, we learned the hard way that "made on shared equipment" labels should be heeded.  Mac n Cheese made on shared equipment with egg-containing foods caused the same reaction.  We were novice food allergy parents, and absolutely heart-broken to have put JR through that terror.  JR was ridiculously sensitive to trace amounts of egg protein).

Fast forward to 2012.  Every year since 2009, JR has been tested through a blood test (RAST) for the presence of antibodies to egg protein.  You know, those same antibodies that protect us from disease?  Well for the food allergic, the immune system erroneously targets innocuous substances like eggs.  This year, the antibody level was at the threshold of being positive.

The antibody (dark green, Y-shaped structure) binding to antigen (light green circle).  In Ian's case that antigen is the "harmless" egg protein.  C'mon, immune system. Since when were eggs worse than the plague?!
Photo source:  http://www.nwfsc.noaa.gov/hab/habs_toxins/marine_biotoxins/detection/elisa.html

Hope, but not proof. 

If only it were as simple as measuring antibody levels in the blood.  Due to the unpredictable nature of the immune system when it comes to food allergies and the large error inherent to allergy testing methods, the definitive proof is the food challenge.  To put it more bluntly, this is the "test" where you go to the doctor's office and consume the offending food... and wait.  Will there be a reaction?

On a very rainy Thursday afternoon, JR and I headed into the doctor's office with 3 hard-boiled eggs and an i-Pad loaded up with Disney movies (for the waiting part).  JR was chipper.  I was terrified.  I remember what happened two and a half years ago.  I'm not sure that JR does. As a scientist, I know this "test" is necessary to confirm the egg allergy is gone (or not), but at that moment, I would have given anything to not have my son be a subject in this test.  But, hey, at least we were in the best place should a reaction occur, right?!

The egg-cellent news

Step 1 - scratch egg into the skin surface and wait (watch the Lion King)... no reaction.
Step 2 - rub egg on lips and wait (Simba just can't wait to be king)... no reaction.
Step 3 - eat a bite of egg and wait (Hakuna Matata)... no reaction.
Step 4 - eat more egg and wait (Lion King done, 4 year old takes over)... no reaction.
Step 5 - try and eat even more egg (4 year old loudly resists)... no reaction.
Step 6 - resort to every form of bribery known to parents to convince 4 year old he should eat more egg... no reaction.
Step 7 - half an egg finally goes down the gullet and Dr. agrees half an egg (instead of a whole egg) is sufficient for the test - no reaction.
Step 8 - relief and a dinner of ice cream and chocolate chips :).

It turns out, we're not quite out of the woods just yet.  Apparently, there is a small chance that the immune system could come back with a roaring vengeance to egg.  For one month, we will avoid eggs altogether.  At the end of the month, JR will be given a blood test to look for antibodies against egg.  If the antibody levels are still extremely low, JR is given the ok to eat egg!  And there will be cake, and cookies, and french toast aplenty.

Scientifically, the immune system is not my area of expertise, but I am in expert in what food allergy parents go through.  As a parent and a scientist, I can't help but wonder why in the world a medical community capable of successfully transplanting vital organs, doesn't have more reliable, indirect methods of allergy testing (e.g. any other test besides the direct food challenge test?!).  What is it that we lack in our understanding?  Finally, if JR has indeed outgrown his egg allergy, what has changed?  What has turned that immune system "switch" off?  If we can understand what turns that "switch" off, then we may just have a cure for food allergies.  I'm not an expert in the immune system scientifically, but I make it my goal everyday to try... for JR and for all of us that are walking on eggshells when it comes to food allergy.

Let's turn the food allergy switch off.