When you suffer from allergies, it starts with an immune system response. It’s this immune response that results in your allergy symptoms, from the runny nose and sneezing to the itchy eyes and hives. But your immune system also responds in ways you can’t see. One of the most significant ways is through the production and release of immunoglobulin E (IgE) and allergen-specific IgE.
What Is IgE?
IgE is a type of antibody created by your immune system. Antibodies are proteins your body makes after being exposed to a virus, germ, or other harmful substance. Designed to recognize and eliminate threats, antibodies fight off these dangerous infection-causing particles and work to keep your body safe in the future.
The body creates antibody IgE in response to allergen exposure. Unlike viruses and germs, allergens are harmless substances that the immune system mistakes as dangerous. Common environmental allergens include pollen, animal dander, and dust mites.
This antibody is found in the lungs, skin, and mucus membranes, and, therefore, these are the areas of the body most likely to be impacted by allergy symptoms.
What Is Allergen-Specific IgE?
Allergen-specific IgE is an antibody the body produces as part of its response to a specific allergen. There are allergen-specific IgE for all allergens, including food, animal dander, pollen, mold, medicines, dust mites, latex, and insect venom.
The presence of allergen-specific IgE may mean that you have an allergic response (the stuffy nose, watery eyes, and itchy skin) when exposed to that allergen. But you may have allergen-specific IgE and not have any visible allergy symptoms.
In most cases, the presence of allergen-specific IgE appears several years before you experience symptoms to a particular allergen. Therefore, allergists use it to predict future allergies. But remember, just because there’s IgE present in your system, does not guarantee future allergy symptoms.
What Does IgE Do?
Like other antibodies, IgE wants to rid your body of the particles it sees as dangerous. In this case, that’s an allergen. To do that, IgE binds to the allergen and two types of white blood cells: mast cells and basophils. This process activates these cells to release histamine and other compounds.
Histamine is a natural compound that causes inflammation. It can result in congestion, watery eyes, stuffy nose, sneezing, coughing, and itchy skin. Histamine creates this type of response in an attempt to get the allergen, what it sees as a harmful substance, out of your body.
Here’s an example, you’re exposed to pollen. Your immune system sees the pollen as a threat and creates IgE antibodies to defend itself. Next time you’re exposed to that same pollen, IgE recognizes it and binds to your mast cells and basophils. This binding activates the cells to release histamine. The histamine travels to your soft tissues, where it causes inflammation that results in your allergy symptoms.
How Does the Body Respond to IgE?
The body can respond in three ways to the production and release of IgE:
- Atopy: The immune system tends to produce IgE after exposure to an allergen, but allergy symptoms do not develop
- Sensitization: The immune system produces an allergen-specific IgE, but allergy symptoms do not develop
- Allergy: The immune system produces an allergen-specific IgE, and the patient experiences allergy symptoms
How Is IgE Used in Allergy Testing?
There are two types of IgE laboratory tests. The first one tests for IgE in the blood and is referred to as total IgE or total serum IgE. The second type of blood work can identify allergen-specific IgE (this is what we use at Wyndly). While total IgE shows that your body is responding to allergens in general, allergen-specific IgE shows what allergen is causing your immune system to react.
Although the body normally has trace amounts of IgE, when levels are high, it can signify that the immune system is overreacting to allergens. High levels of IgE may also mean that the body is fighting a parasite infection. Although total IgE has traditionally been used to confirm allergy conditions, its ability to identify allergies and allergic diseases has been poor.
Currently, IgE is used in the testing for and diagnosing of allergies. Doctors can tell if you’ve had an immune response by looking at the IgE and allergen-specific IgE levels in your blood. Although total IgE blood levels do indicate the possibility of allergies, allergen-specific IgE testing is needed to identify what is causing your reaction.
To complicate matters more, just because there’s the presence of an allergen-specific IgE, it does not mean that you have a meaningful allergic response to that substance. Unless you develop allergy symptoms, the presence of an allergen-specific IgE does not determine an allergy. Instead, it just determines a sensitization to the allergen.
So that means total IgE shows that your body is responding to allergens in general, while allergen-specific IgE frequently shows what allergen is causing the immune system reaction.
IgE Antibody Levels
When you have an IgE blood test, your IgE serum levels will be cited as normal or high.
What Is a Normal Level of Total Serum IgE?
Most people have some level of IgE in their system at all times. The normal range is from 2-150 IU/ml. But just because you have a low level of total serum IgE does not mean you won’t have some type of allergic reaction. It just means it’s less likely.
What Is a High Level of Total Serum IgE?
If your bloodwork shows an elevation in total serum IgE, say above 200 IU/ml, it may mean you have allergies, but not necessarily. This elevation could be caused by other conditions like:
- Allergic disease
- Primary immunodeficiencies
- Parasitic infection
- Viral infection
- Certain inflammatory diseases
Because total IgE is present in those with allergies, as well as those with other conditions, its presence alone is not enough to diagnose allergies. That being said, those patients with elevated total IgE levels are more likely to develop allergies than those with normal levels. It doesn’t mean these patients will develop allergies. It just means they’re more likely to than someone whose total IgE remains within the normal range.
Furthermore, research indicates that when a newborn’s cord blood has elevated levels of total IgE, they are at a higher risk for developing food allergies, dermatitis, and seasonal allergies. In early childhood, higher above average IgE levels may be a predictor of future allergy conditions. But, as previously mentioned, this is only a predictor and indicates an increased risk, not a diagnosis.
What Is the Ratio of Allergen-Specific IgE to Total IgE?
Coined the “specific activity,” the ratio of allergen-specific IgE to Total IgE is sometimes used to diagnose allergy-related conditions. Specific activity is also used to predict a patient’s response to anti-IgE therapy. In some cases, this ratio is no more useful than allergen-specific IgE, while other times it can identify a reduced response to clinical therapy.
Can IgE levels Be Reduced?
Most traditional allergy medicines don’t address the immune system’s response to allergens. Instead, these medications focus on reducing your allergy symptoms. In many cases, over-the-counter medications, such as antihistamines, work by blocking the release of histamine by mast cells and basophils.
More modern allergy advancements like immunotherapy don’t necessarily reduce IgE, but instead move the body from the allergy stage to sensitization or atopy, eliminating allergy symptoms. Sometimes, depending on dosage and timing, immunotherapy can increase or decrease IgE levels within the body, all while still reducing symptoms.
Newer treatments like anti-IgE therapy use pharmaceutical antibodies to reduce the impacts of IgE. For instance, omalizumab, sold under the brand name Xolair, binds to IgE in the body, stopping it from binding to mast cells. This medication is currently FDA approved to treat allergic asthma and chronic urticaria (spontaneous hives). Research on its impact on seasonal allergy symptoms, eczema, and other allergy conditions is currently underway.
IgE in Specific Conditions
The role of total IgE and allergen-specific IgE differs among the varying allergy conditions.
Children and adults with asthma tend to have higher levels of total IgE than those who don’t have asthma. One study showed that patients who didn’t have any allergies but did have total serum IgE levels greater than 150 IU/ml have a five times greater risk of having asthma than those with normal IgE levels. IgE levels also correlate with the severity of asthma. Studies also show that total serum IgE levels rise proportionately in asthmatics with lower lung function.
What’s more, allergic asthma responds well to anti-IgE therapy. Most patients see a reduction in symptoms, including reduced exacerbations and decreased inflammatory markers.
Allergic Bronchopulmonary Aspergillosis
Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction that occurs in the lungs after being exposed to fungal spores. It’s typically seen in patients with asthma or cystic fibrosis. It is one of the few diagnoses that use total IgE values.
These patients have highly elevated IgE levels, reaching greater than 417 IU/ml in those with asthma and greater than 1,000 IU/ml in those with cystic fibrosis](https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-allergic-bronchopulmonary-aspergillosis#!). When a patient’s aspergillosis condition flares, the total serum IgE level increases.
Allergic rhinitis describes the common symptoms that develop with seasonal allergies. Sometimes called hay fever, allergic rhinitis includes cold-like symptoms like runny nose, itchy eyes, nasal congestion, sneezing, and sinus pressure. Those with this condition do have elevated levels of allergen-specific and IgE blood tests are frequently used to determine allergens for immunotherapy and allergy treatments.
Atopic dermatitis, commonly referred to as eczema, is an allergic response that manifests in red, itchy skin. Eczema tends to be chronic, and it goes through periods where it gets worse and then goes into remission. While atopic dermatitis is an allergic response, 30% of patients with this skin condition do not have any other allergy symptoms. They may also test negative on an allergy skin prick test.
Although 80 to 85% of patients with eczema have elevated levels of total serum IgE, it is not necessary for a diagnosis of the condition. In children, high levels of IgE (those reaching greater than 10,000 IU/ml) can indicate a greater risk for severe eczema, food sensitivities, and anaphylaxis.
For those with food allergies, assessment of IgE is useful to determine the risk of immediate allergic reactions, like hives, wheezing, or anaphylaxis. Although IgE levels should not be solely used to determine the diagnosis of a food allergy, they can be helpful in combination with the patient’s clinical history.
Many doctors now opt for IgE testing in lieu of challenge testing, the traditional method of determining food allergies. In a challenge test, the patient is exposed to the allergen in question and waits to see if the immune system reacts. This is done in a controlled environment (often the doctor’s office) and emergency medicine is on hand in case of severe reaction or anaphylaxis. By using a food-specific IgE blood test, along with the patient’s previous experiences and medical history, this risk is eliminated.
If you’ve had an allergic reaction to a stinging insect, such as a bee or wasp, you may have a venom allergy. Blood tests for venom-specific IgE are used to confirm the allergy, especially in cases when the skin prick test failed to show results.
Chronic urticaria is the medical term for hives that don’t go away. This allergic skin reaction can last for a few weeks to several months. There is no evidence of high levels of IgE, but in about 40% of cases, patients have elevated levels of IgG, an antibody similar to IgE but created in response to viruses and bacteria instead of allergens. Even though IgE is not associated with the condition, anti-IgE therapy is effective and widely used for reducing urticaria symptoms.
While the release of allergen-specific IgE is an integral part of the pathology of allergies and allergic diseases, its role in diagnostics varies. As you can see, most patients with allergies and other allergy conditions have high levels of total IgE, but there is no threshold that one group is above or below, as there is considerable overlap in IgE levels.
But that does not negate the importance of IgE in diagnostic procedures. Allergy blood tests, like those offered through Wyndly, are highly effective at determining specific allergens, especially when paired with a patient’s clinical history. If you’d like to learn more about IgE testing and what it can do for your allergies, schedule a consultation today.