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June 8, 2020

The Science Behind Allergy Diagnostics

When it comes to diagnosing food allergies, there are two tests that healthcare providers typically turn to: skin-prick testing and specific IgE (sIgE) blood testing. On the surface, both seem fairly simple. But have you ever wondered what these tests are actually measuring? And how, exactly, they aid in the diagnosis of a food allergy?

Well, you’ve come to the right place. Refresh your beverage, log out of Twitter, and settle in as we present a deep dive into the science behind allergy diagnostics. Things might get a little bit complicated, but we promise we’ll make the ride as smooth as possible.

We’re going to let you in on a secret: To really understand allergies and how they are diagnosed, we need to discuss the immune system. Yep. That immune system. The one you use to fight colds, flus, and everything in between.

Let’s start with something called Immunoglobulin E (IgE).

What is IgE?

Like a military base, our immune systems contain a complicated network of defenders that work together to keep us healthy. Some of those defenders are called immunoglobulins, aka antibodies, which bind to pathogens like viruses and microbes to disable them. You have probably heard of these little guys in relation to things like the common cold or infections that your body fends off. The same sort of “army” is called up to deal with allergic triggers.

Allergies happen when our bodies produce elevated levels of a certain type of antibody defender, called IgE, to fight off the perceived threat of an allergen.   

We’re getting ahead of ourselves. Time for a quick history lesson.

IgE was discovered in 1967, when researchers found that people who had allergic reactions to substances that were not typically harmful (think pollen or milk) had elevated levels of specific IgE antibodies in their blood.1 The symptoms of an allergic reaction are triggered when the IgE antibodies interact with an allergen, and signal the release of chemicals, including histamine. This dangerous dance can lead to everything from hives and itchy eyes to anaphylaxis.

What is allergic sensitization?

People who produce elevated sIgE that can recognize a specific allergen are described as being “sensitized” to the allergen. Having an increase in sIgE is correlated with an increased likelihood of having an allergic reaction when exposed to that allergen.

But sensitization doesn’t guarantee that the person will definitely have an allergic reaction. In the case of food allergies, it also doesn’t indicate that a food should be completely removed from a patient’s diet, especially if the patient is currently eating the allergen without problems.

At the molecular level, IgE antibodies don’t actually react to whole foods. There is no alarm screen that says “WARNING: PEANUT” or “INTRUDER DETECTED: EGG.” Instead, IgE antibodies are recognizing, and interacting with, small fragments of each allergen. In the diagnostic world, these fragments are called allergen components.

We know what you’re thinking. “What are allergen components?” We’ll tell you!

What are allergen components? 

Let’s think of a whole allergen, like a peanut, as a big puzzle. Each piece of the puzzle is usually a small part of a protein that could be recognized by an IgE antibody. We call these different puzzle pieces “components” and the diagnostic tests that recognize them “component tests.” In most cases, a specific allergen component binds to the IgE antibody that recognizes it and not any others, similar to a key fitting into a lock.

Allergen Component

Not every person that’s allergic to peanuts is allergic to the same components of the peanut. In other words, people with so-called “peanut allergies” may be reacting to different puzzle pieces. Scientists aim to identify the specific biological components involved in allergic reactions because identifying them can help patients better understand and manage their allergy. 

For peanut allergies, this knowledge can help inform a patient if they’re likely to only experience less severe symptoms, such as an itchy mouth, or if they are at increased risk for having an anaphylactic reaction, which may require additional precautions such as strict avoidance of all peanut products and carrying an epinephrine autoinjector.2 And in the case of m‌ilk or e‌gg allergies, component testing can help inform a patient of how likely they might be to tolerate their allergen in baked form. That’s right, you could have an e‌gg allergy but still be able to consume a slice of cake. Science!

OK that’s all well and good, but why are some proteins more likely to cause a minor reaction, while others cause a more severe reaction? We’re glad you asked. The answer is both simple and a bit vague: All proteins are different. Proteins are often organized into groups called “families” based on their molecular characteristics.

Some protein family members “look” so similar that the body can mistake one for the other. Ever heard the phrase, “Shoot first, ask questions later”? If your immune systems perceives a protein as a threat, IgE antibodies will get to work. This case of mistaken identity is called cross-reactivity, and it can affect how the body responds to allergens. But that’s a topic for another post.

Let’s get back to testing, shall we?

Component tests vs. whole allergen tests

Now that you know what allergies have to do with the immune system, it’s time to reveal how component tests differ from whole allergen tests. 

In a whole allergen test (commonly done with skin prick testing or via blood testing), all of the “puzzle pieces” are present in the test. That means it’s impossible to determine the specific component to which a patient with a positive result is sensitized. Why does that matter? Remember when we talked about peanuts, eggs, and milk? And how being sensitized to one protein and not the others could impact the patient’s life? Only component testing can identify which specific proteins or molecules may be triggering reactions. As more and more of these components are identified, and new tests become available, people can gain more knowledge about their specific “allergic fingerprint,” and this can help them better manage their allergic disease.   

Click on the allergens below to learn what allergen component testing can tell you:

By understanding patients’ allergies at the molecular level, healthcare providers can help patients better understand their allergies and identify patients who are the best candidates for an oral food challenge.2  Diagnostics are powerful tools, but ultimately a patient’s physical response to consuming a potential allergen is the only way to truly rule an allergy in or out.3

So … that’s it?

Phew. That was a lot, but you made it.

While we can’t give an exam to measure how well you retained the information (nor do we want that pile of paperwork), we do want you to feel empowered and informed so that the next time your healthcare provider mentions diagnostic testing, you’ll have a better understanding of why the test is valuable, and what it measures. Just remember that you should always discuss your test results and allergy management plan with your healthcare provider. They are the true experts in creating personalized allergy diagnosis and allergy management plans. Blog-End-Cap.png

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References
  1. Platts-Mills TA, Heymann PW, Commins SP, Woodfolk JA. The discovery of IgE 50 years later. Ann Allergy Asthma Immunol. 2016;116(3):179–182.
  2. LaHood NA, Patil SU.  Food Allergy Testing.  Clinics in Laboratory Medicine. 2019; 39(4): 625-642.
  3. Schussler E, Kattan J.  Allergen Component Testing in the Diagnosis of Food Allergy.  Current Allergy and Asthma Reports. 2015; 15(9): 55.