Blood Serum IgE Testing

IgE is an antibody that plays a key role in activating allergy cells when also appropriately bound by its specific allergen

Immunoglobulin E, called IgE for short, is one type of antibody (which simply is an immune protein that is produced after the body is exposed to a substance, for a purpose that is connected with the type of antibody produced). Antibodies generally have the interesting ability to bind to the same substance that caused them to be produced in the first place and then have their intended effect. The IgE antibody is part of the pathway that activates cells classified as allergy cells (like mast cells or basophils). Activated allergy cells cause the symptoms we associate with various types of allergic reactions, such as increased mucus production, coughing, swelling, watery eyes or a runny nose, itching, etc.

Allergy cells contain IgE receptors on their surface, and these serve as binding sites for IgE antibodies. The binding of IgE antibodies to their receptors on allergy cells does not cause an allergic reaction on its own. Rather, it primes the allergy cells, making them ready to react when enough of the appropriate allergens are around as well. The special pattern of binding between an allergen substance and its IgE antibodies on allergy cells that provides the signal to activate the allergy cell is called “cross-linking”, and the release of the allergy cells contents (and the symptoms that ensue because of these contents, including histamine) are what we call an allergic reaction.

Sometimes, IgE antibodies bind to allergy cells nearby after they are produced. Other times, IgE antibodies travel through the bloodstream throughout the body and then leave the blood vessels in different places to find allergy cells in those other areas. The most common allergy cells are mast cells (found in body tissue areas like the skin, nose, eyes, airways, GI tract, brain and central nervous system, but notably not in the blood) and basophils (typically found in only small numbers in the blood, but they can be recruited out into body tissue areas too).

Measurement of IgE antibodies in the blood is used as a substitute marker to estimate what we really want to know (which is how “primed” your allergy cells are and with which specific IgE), and it is far from always accurate

A great allergy diagnostic test to have regarding IgE would be a measure of the total and specific IgE antibodies bound to their receptors on your allergy cells, priming these allergy cells to become easily activated when the appropriate allergen is also present, causing an allergic reaction. Since getting this type of information would require quite invasive techniques at the current time, there is no available clinical test for this, and measuring the amount of IgE in the blood instead is used as the best available substitute.

In many instances, blood IgE provides good insight about IgE on allergy cells, and test results clearly correlate with a person’s allergic reactions and symptoms. However, in many other instances, symptoms, allergen skin tests, and blood IgE tests may not appear to suggest the same things about a person’s allergies, and using the blood IgE marker for diagnostic purposes becomes very complicated given its limitations.

It is further complex to gather useful information from blood IgE tests in the context of doing a treatment that is designed to actively change the immune system, like any form of immunotherapy. Immunotherapy causes changes in so many factors, like the number of IgE receptors present your allergy cells, the amounts of other antibodies (like IgG4) produced, the amount of IgE produced, etc – all of which affect blood IgE numbers in different, sometimes conflicting, ways.

The amount of IgE present in your blood varies constantly due to many factors, only some of them related to how allergic you are

A blood IgE test gives us only a snapshot in time regarding IgE in your blood. The IgE found in your blood when a lab test is run depends on many things beyond how much IgE is being produced by your immune system, like how much and what types of allergen you are encountering in your environment, the state of your immune system overall (is it overwhelmed, activated, suppressed, or calm), your age range (IgE production naturally increases throughout childhood and generally decreases over time in adulthood), the availability IgE receptors on allergy cells, which lab your tests were run in (machines can be calibrated very differently in different labs), and more.

If you had your blood IgE levels checked every day for a week, the values would not be exactly the same each day. If they were checked every season, some differences would be related to seasonal allergen exposures. If they were checked every year during childhood, some changes would be purely due to growing older. If checked when you are healthy and when you are ill, changes would be expected. And when checked periodically while on immunotherapy, some changes are secondary to the effects of immunotherapy.

Checking a new total blood IgE level each time specific IgE tests are to be interpreted is often helpful for some additional context due to these natural or influenced fluctuations in IgE production at different times.

A high blood IgE level to an allergen doesn’t necessarily indicate that you are allergic, and a low or “negative” blood IgE level doesn’t necessarily indicate that you are not. Blood IgE tests require interpretation within a much larger context to have meaning

At Allergenuity Health, we spend the time to collect and carefully consider your medical history, environmental influences, immune system function, and important test-related factors in order to provide you with a thoughtful interpretation of what a specific blood IgE result may mean for you (or your child).

We all wish that a “negative” blood IgE simply meant that you are not allergic, a low blood IgE meant you are only mildly allergic, and a high blood IgE meant you are very allergic. If this was the case, blood IgE would be a great diagnostic test, and tracking blood IgE levels of time would clearly tell us if your allergies were getting worse or better. (And our job would be so much easier!) However, that is unfortunately not the case. Even though this is how blood IgE tests are sometimes used by companies selling allergy treatments and even some providers running these tests, using blood IgE tests this way gives an overly simplistic and possibly incorrect interpretation of what your results mean, and this can lead to misdiagnosis, treatment mismanagement, and a lot of frustration and confusion.

A high amount of IgE in the blood for an allergen only suggests that you may be also highly sensitized for that allergen – meaning that there is a lot of IgE to that allergen also bound to your allergy cells, priming them to react very easily when also in contact with the allergen. However, that is certainly not always the case, such as when a specific type of IgE gets produced in large amounts but does not bind properly to allergy cells, or when there are either not a lot of available IgE binding sites on the allergy cells or just not many IgE receptors in general (as may be the case in a tolerant or calm immune system).

Likewise, a “negative” or low amount of IgE in the blood only suggests that there may not be much IgE on your allergy cells, but does not confirm this to be true. An example of this is when IgE binds to nearby allergy cells after it is produced, bypassing the need to travel through the blood in any substantial numbers. So there may not be much IgE present to a particular allergen in the blood, but it could be present in high amounts on nasal allergy cells causing severe nasal allergy symptoms in the presence of that allergen, for instance.

Additionally, commercial tests for blood IgE may also be lacking the ability to detect the exact type of specific IgE that your body has produced towards an allergen because these tests of course cannot measure everything, so they are set up to measure what they can and what is most common.

As if all of this doesn’t make the meaning of blood IgE numbers confusing enough, being sensitized to an allergen (having your allergy cells primed to react to that allergen due to already bound IgE) does not even necessarily mean you are allergic

So…  the presence of IgE in the blood suggests that you are sensitized, but does not guarantee it. And being sensitized suggests that you are allergic, but does not guarantee it?? That makes blood IgE results at least 2 important steps removed from a diagnosis of allergy.

Being defined as allergic to an allergen means that there is enough clinical and/or test evidence to suggest that in the presence of an allergen, your allergy cells are at a decent risk of being activated causing you to have symptoms. As you can see from this definition, there is really no one type of test that alone would always be able to diagnose an allergy.

You have probably heard instances of people getting blood IgE tests done and having a high IgE number to a food that they say they eat all the time without ever having a reaction. An example would be someone with a peanut IgE of 158 kU/L who eats peanut butter all the time. So are they allergic to peanut or not? One way this situation could occur is if that person is only allergic to a component of peanut allergens that cross-reacts strongly with birch tree pollen. This particular peanut allergen component is a weak allergen because it breaks down easily with heat and digestion. Therefore, even if the body is producing IgE to it, or if some allergy cells are primed to react to it, the allergen may not even reach those primed allergy cells in large enough or functional enough amounts to cause a reaction. So, depending on several other factors that could also play a role, that person may not necessarily need to be labeled as allergic to peanut or need to always avoid it.

Another fun fact about blood IgE – levels often first go UP on immunotherapy treatment of any form

No one likes to see blood IgE levels go up because it is everyone’s gut reaction that an increasing IgE number indicates a worsening of allergy. However, it is important to understand that increasing blood IgE levels are not always an indicator of something bad, and merely suggest that changes have taken place within the immune system – changes that could be bad or good or neutral. Other contextual aspects are important to help figure out which one it is.

Studies have very clearly shown the phenomenon of immunotherapy (of any type) correlating to and appearing to cause increased blood IgE levels while also, at the exact same time, significantly improving the person’s symptoms. The mechanisms of all forms of immunotherapy are complex and still being studied for more exact information, so further detailed explanations about why exactly this phenomenon occurs will hopefully be available in the future. For some people, their blood IgE levels continue to increase on immunotherapy and they never decrease, though their symptoms and allergen tolerance improve significantly. For others, blood IgE levels go up at first, generally over 2-3 years, and then may decrease some – sometimes remaining higher than they started, other times decreasing to much lower than their initial levels.

Clear as mud, yes?

Proper interpretation of blood IgE test results by someone knowledgeable about all these nuances, like a trained allergist, is extremely important when using blood IgE results to help guide the diagnosis and treatment of allergic disease

At Allergenuity Health, we approach the review of blood IgE tests in the context of everything we discussed earlier on this page and more. Dr. Schroeder gives a lot of her time to the review of your (or your child’s) blood IgE test results in order to assess them in the most complete context to best determine what information they may provide for your specific circumstances. Blood IgE tests can be another very helpful as a piece of the puzzle. We want you to feel comfortable understanding what these blood IgE numbers really do and do not tell you about your allergies as best as possible, and also to show you why it is so important to not care more about what your exact blood IgE numbers are than all the other factors that tell us more about your actual health and allergic status than these blood IgE numbers – like how you are feeling overall, hopefully how well your chronic symptoms are controlled now compared to previously, how much less you reacted to an accidental food allergen exposure than before, etc.

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