The ABCs of IgEs

Defining Immunoglobulin E, Debunking Antibody Myths, and Delving Into My Updated Bloodwork

“Another primary reason for misdiagnosis is a lack of understanding of what the results of serum IgE testing truly mean. In the absence of clinical IgE-mediated symptoms with ingestion of the food, a positive serum IgE test to that food merely means a patient is sensitized to it.”

Fleischer & Burks (2015) – Pitfalls in Food Allergy Diagnosis: Serum IgE Testing

Just two years ago, I had a life-changing appointment at Chicago Family Allergy and Asthma, walking into the routine check-up with a laundry list of severe food allergies and walking out with only one. Prone to passing out during blood draws, I had put off the visit for nearly five years – Why the sense of urgency if I wasn’t expecting to hear anything new? Well, my IgE levels certainly had a different idea in mind.

In my blog post, And Then There Was One, I detail the journey of how All Things Allergies nearly became All Things Allergy with the big reveal of my undetectable bloodwork. I remember answering the phone call with my results like it was yesterday, quickly cycling through the five stages of grief.

This cannot be right. I’m going back to the office for a confirmatory scratch test. Denial. Why didn’t I make this appointment earlier?! Anger. I should just keep avoiding them though, right? Bargaining. I feel like an imposter. Depression. Your body just offered you the most beautiful gift. Acceptance.

But what significance did those digital decimal points really have, anyways? While I understood my allergist to be the expert on the topic, my survival instincts blinded me with skepticism. After steering clear of tree nuts for twenty-four years as if my life depended on it (Because, it did), how could I place enough trust in these numbers to unravel the strict avoidance I’d maintained for two decades?

Well, knowledge is power.

What is Immunoglobulin E?

Immunoglobulin E (IgE) represents a category of antibodies produced by the immune system. When the body encounters a potential allergen, it can generate allergen-specific IgE antibodies, initiating what is known as the sensitization process. Upon subsequent exposure to the same allergen, these antibodies attach to the immune cells in the body, prompting the release of histamine chemicals into the bloodstream. This process constitutes the underlying mechanism of an allergic reaction.

The presence and concentration of these antibodies can be measured through simple scratch tests and/or bloodwork, making IgE testing a common ingredient of allergic syndrome diagnostics.

Skin prick testing, or scratch testing, involves the introduction of a small amount of allergenic substance into the skin. Generally performed on the back or inner forearm, the test takes about fifteen minutes and can offer immediate, in-office results. Sensitivity to the allergen is measured by hive, or wheal, size in millimeters. Physicians have the ability to test for nearly 150+ allergies using skin testing, but the method is not recommended for those with severe skin conditions, like eczema or dermatographia. And, it’s likely you’ll be walking out of the office with a slathering of antihistamine cream across the testing site.

A standard blood draw can detect the concentration of allergen-specific IgE antibodies in the bloodstream, measured in kilounits of allergen-specific IgE per liter (KUA/L). The number of allergens that can be evaluated through serum testing is more limited, and the results tend to have a longer turnaround time from the laboratory. Although this assessment is more expensive, it carries only one needle prick and leaves behind the risk of itching.

Both tests are accompanied by their own merits, offering the provider and patient with greater insight into allergic conditions. The two may be used independently or in combination with one another, but should not be ordered until a convincing history of potential IgE-mediated symptoms has been established.

Allergic Nuance

Throughout childhood, I had no concept of this diagnostic process. I attended the appointments, suffered through the needle pricks, and then simply adhered to whatever my allergist prescribed. Epinephrine, strict avoidance… Allergies felt binary – Either I was allergic to something, or I was not. But this rudimentary understanding ignored many of the intricacies of food allergy diagnostics.

It wasn’t until I had the adult responsibility of monitoring my own electronic medical records that I grew curious of the vague numbers that populated within it. And take it from me – The girl who unexpectedly encountered a slew of zeros across her chart at age twenty four – Allergy testing is much more nuanced than we have been made to believe.

Let’s debunk some of these misconceptions.

Myths of IgE Testing

Myth: IgE testing is diagnostic.

Nope! Blood serum and skin prick testing are popular and powerful tools, but they are not independently diagnostic. A review of medical history and past symptomatology can better inform the collected IgE results, but a double-blind oral food challenge is consider the “gold standard” for diagnosing food allergies.

Myth: A positive IgE test result means that you are allergic to that food.

Not exactly. According to FARE, blood and skin prick tests yield a 50 – 60% false positive rate, meaning that tests can indicate that you have an allergy to something that you are not actually allergic too. This partly informs why IgE tests are not diagnostic, and results should be interpreted in the context of other findings.

According to an article in the Journal of Pediatrics, “Another primary reason for misdiagnosis is a lack of understanding of what the results of serum IgE testing truly mean. In the absence of clinical IgE-mediated symptoms with ingestion of the food, a positive serum IgE test to that food merely means a patient is sensitized to it…. The key to the diagnosis of food allergy cannot be overstated; it begins with a detailed clinical history and then physical examination.” Past symptomatology matters!

Myth: All blood tests are created equally.

Not true. Allergen-specific IgE serum testing looks at whole allergens, while component testing looks at individual allergen proteins. Using this technology, component testing can specify which specific proteins in the allergen you are sensitive to. For more on this topic, check out my personal experience with component testing in a recent collaboration with Allergy Insider and Spokin: Allergy Component Testing: Alyssa’s Story.

Myth: IgE blood testing can predict the severity of a potential allergic reaction.

Wrong again! IgE levels cannot predict the severity of a potential allergic reaction. This was clearly articulated by Fleischer & Burks (2015), who wrote “Many individuals wrongfully correlate the food-specific IgE level with the probability and/or severity of reacting to that food.” Instead, IgE levels represent sensitivity, or the likelihood that the allergy exists. IgE blood work simply measures the concentration of antibodies present in the bloodstream, rather than allergic thresholds.

Myth: IgE testing is affected by antihistamine medications.

Yes, and no. According to FARE, IgE blood testing is not affected by antihistamines. However, skin prick testing is, and your allergist may recommend you stop taking those medications several days before your scheduled appointment.

Myth: Immunoglobulin E (IgE) is exclusive to allergic syndromes.

It’s true that this type of testing cannot diagnose intolerances or food sensitive, but that certainly does not make it exclusive to IgE-mediated allergies. IgE plays a role in the body’s natural defense system against parasites, autoimmune diseases, and other medical conditions.

Updated Bloodwork

Having learned my lesson last visit, I am now committed to following up with my allergist every two years for updated bloodwork. In August of 2023, I braved my needle phobia and had the lab run a full food and environmental allergy panel. Thankfully, a more complete understanding of Immunoglobulin E helped me better interpret the results received at that appointment.

In childhood, I was prescribed strict avoidance of peanuts, tree nuts, fish, and legumes. Repeated testing revealed that between the ages of 18 and 24, my tree nut and fish antibodies seemed to naturally dissipate – A rare occurrence, but a miracle that I am continually grateful for. My concentration of peanut antibodies followed suit, decreasing from >100.00 KUA/L to 44.7 KUA/L during that same timeframe. Despite the decline, component testing confirmed that I was still very much allergic to the individual peanut proteins responsible for severe reactions.

Fast forward to August of 2023, two years and an anaphylactic reaction later, peanut has shot back up to >100.00 KUA/L.

Comparison of Peanut IgE Levels at Ages 24 and 26

Honorable mention goes to cats, dogs, dust, and cockroaches, who all fell in the 5 – 10 KUA/L range. A more comprehensive list of my past results is linked in my blog post here.

My immediate reaction to the spiked levels was clouded by fear – My allergy is getting worse?! Well, maybe not. Keeping the ABCs of IgEs in mind, this number does not represent the severity of my food allergy, nor does it predict the severity of a potential allergic reaction. Rather, it simply measures the concentration of antibodies in my bloodstream.

Okay, but did my recent allergic reaction skyrocket the antibodies? Well, it seems like the jury is still out on that one. According to a 2016 study published in the Journal of Allergy and Clinical Immunology Practice, accidental exposure to milk, egg, or peanut that resulted in allergic reactions in children was not associated with significant increases in wheal size or allergen-specific IgE levels. However, in more recent study published in Clinical and Experimental Allergy, IgE levels specific to the ingested allergen increased following an anaphylactic reaction.

Does anyone have further insight into this connection? I’m quite interested in researching further.

But until then, everything else is still sitting pretty at ‘Undetectable?’ Great! I’ll check back in two.

Resources:

1. Children’s Hospital of Philadelphia. IgE Mediated Food Allergies. Retrieved from https://www.chop.edu/conditions-diseases/ige-mediated-food-allergies
2. Food Allergy Research and Education. Blood Tests. Retrieved from https://www.foodallergy.org/resources/blood-tests.
3. Food Allergy Research and Education. Skin Prick Tests. https://www.foodallergy.org/resources/skin-prick-tests
4. Fleischer, D. & Burks. A. (2015). Pitfalls in Food Allergy Diagnosis: Serum IgE Testing. The Journal of Pediatrics, 166(1), 8-10.
5. Lemons, L. (2021). A Guide to Understanding Allergen Component Testing. Allergy Insider. Retrieved from: https://www.thermofisher.com/allergy/us/en/living-with-allergies/testing-and-diagnosis/guide-to-allergen-component-testing.html.
6. Rehimini, S., Gabrielli, S., Langlois, A., Clarke, A., De Schryver, S., McCusker, C., Bretholz, A., Zhang, X., Shand, G., and Ben‐Shoshan, M. (2021). Clinical and Experimental Allergy, 51 (2), 364-368.
7. Sicherer, S., Wood, R., Vickery, B., Perry, T., Jones, S., Leung, D., Blackwell, B., Dawson, P., Burks, A., Lindblad, R., & Sampson, H. (2016). Impact of Allergic Reactions on Food-Specific IgE Concentrations and Skin Test Results. J Allergy Clin Immunol Pract, 4(2), 239-245.

Disclaimer: The content of this post is for educational purposes only, and should not be substituted for medical or professional advice. Please consult with your doctor for more information.