About 50 years ago, the discovery of IgE marked a new era in immunology. This antibody shields against parasites and cancer but also triggers intense allergic reactions. Learn the details about IgE roles in the body, blood test, normal range, high and low levels, and more.
What Is IgE?
Immunoglobulin E (IgE) is a type of antibody. Our immune cells called B cells (or plasma cells when activated) produce antibodies in response to allergens, pathogens, cancer cells, and other threats. Antibodies help our immune cells recognize and remove these “intruders” [1, 2].
The primary role of IgE is to protect your body from worm and other parasite infections. It is also involved in allergic reactions [3, 4].
Scientists assume that IgE flags all kinds of unwanted components, acting as the “gatekeeper” of our immune system. In response to these components, T immune cells release cytokines IL-4 and IL-13, which stimulate the production of IgE antibodies [5, 6].
Allergies
Source: Wright et al., 2015
IgE mediates the most common allergic reaction, known as type 1 hypersensitivity. This is an uncontrolled immune response to components in the environment (antigens) in allergic diseases such as [7]:
- Asthma
- Atopic dermatitis (eczema)
- Allergic rhinitis (hay fever)
- Food allergies
An allergic person produces specific IgE antibodies to an allergen during the first contact, known as sensitization. These antibodies bind to immune cells (mast cells and basophils), enabling them to recognize the allergen next time [8].
Next time the same allergen reaches the body, massive amounts of IgE stimulate mast cells and basophils to release histamine and other “defense weapons.” This results in unpleasant symptoms ranging from skin itching to life-threatening conditions [9, 10].
Our B cells produce a specific type of IgE for each allergen, and that’s why you can be allergic to only one thing, such as peanuts, or a couple of them [11].
Parasitic Infections
This antibody evolved as our defense mechanism against parasitic infections. The presence of parasites (helminths) in your body triggers vigorous IgE production [6].
The resulting chain reaction also involves mast cells, and it’s meant to destroy and remove the intruder. But this time, the threat is real, the response is fine-tuned, and it helps us stay healthy.
Other Roles
IgE may be crucial for our antiviral immune response, although this role is less studied. Scientists have identified human IgE antibodies against some respiratory viruses [12, 13].
Emerging evidence voices the importance of these antibodies in cancer prevention. They flag cancer cells and help our immune system remove them before they start spreading [14].
Indeed, higher levels of IgE may protect you against some types of cancer (more details below).
IgG vs. IgE
IgG immunoglobulins are our main antibodies, accounting for approximately 75% of the total amount. They shield us from infections by flagging all kinds of pathogens, such as bacteria, viruses, and fungi [15].
On the other hand, IgE is present in tiny amounts under normal conditions, and it’s specialized for parasitic infections.
IgE is involved in a common, more immediate allergic reaction (type 1). These reactions are either evident straight away or take up to 4 hours after exposure [16, 17].
IgG plays a central role in type 2 and 3 allergic reactions. These typically take a longer time to develop and include certain food and drug allergies [16, 17, 18].
IgG antibodies can also be anti-inflammatory and indicate tolerance (not sensitivity!) to specific foods. That’s why IgG-based food sensitivity tests don’t work [16].
IgE Blood Test
Test Types
You usually get an IgE blood test when you have recurring infections or to monitor immune disorders such as allergies.
New methods, such as ImmunoCAP (based on fluorescence), have been replacing the standard one called RAST (based on radioactive tracking).
These new methods are more sensitive and, besides total IgE levels, they also detect and measure specific IgE antibodies with up to 98% accuracy. This feature can aid in the diagnosis and management of allergies [19].
For example, testing for specific IgE might replace food challenges in diagnosing food allergies [20, 21].
On the other hand, total IgE is not a specific marker and can’t be used to diagnose a particular disease. It can, however, point to certain clues, such as the risk of allergies, infections, and some chronic diseases [22].
Normal IgE Levels
IgE has the lowest concentration of all antibodies, especially in people without allergies. Normal values may vary in the scientific literature, but the usual reference range is 1.5-144 kU/L (IU/mL) [1, 23].
However, most labs have a limit of detection at 2-2.5 kU/L, under which levels are considered low [24, 25].
In studies on over 15K people, most healthy adults had IgE levels below 150 kU/L while the average value was around 27.2 kU/L [23, 26].
Men typically have higher IgE values than women, with up to 20 kU/L difference [27, 23, 26].
IgE levels increase through childhood, peak at 10-15 years of age, and then start dropping as we get older. In a study on over 500 preschool children, the average value was 80 kU/l [28, 29].
Other factors that influence IgE levels include [28, 30, 23, 31]:
- Genetics
- Race
- Smoking
- Alcohol consumption
- Environmental factors
- Immune status
Limitations
As many different conditions can increase total IgE, it’s not suitable for diagnosing a particular disease or even allergies in general [27, 32].
Low levels are a bit more specific, but they too can’t confirm the exact type of immunodeficiency without additional tests [22, 33].
Being unspecific, the cost-effectiveness and the routine clinical use of total IgE blood tests is questionable [34].
When it comes to allergies, skin prick and patch tests remain the first choice. They are sensitive, suitable for most allergens, more convenient, and cheaper than a total IgE test [35, 36].
High IgE Levels: Causes and Associated Conditions
What Do High IgE Levels Mean?
IgE levels are a marker of immune health. Low or high levels don’t necessarily indicate a problem if there are no symptoms or if your doctor tells you not to worry about it.
According to most labs, IgE levels above 150 kU/L are considered high. Children and women usually have lower levels, but it depends on other factors discussed below.
1) Allergies
Allergies are the most common cause of elevated IgE. IgE increases in response to allergens, which are different for each person. For some, the triggers are dietary (food allergies), and for others they are seasonal (pollen allergies) [37].
Total IgE is not a sensitive lab parameter, but levels above 200 kU/L often indicate the presence or an increased risk of allergy [3, 38, 39].
According to a study on over 8K people, IgE > 100 kU/L increases the chance of atopy (allergic tendency). In 1300 Asian children, the limit was even lower: 77.7 kU/L [26, 40].
Eczema, Asthma, and Hay Fever
Atopic dermatitis or eczema generally causes the highest IgE levels, followed by asthma and hay fever. In a study on Chinese children, those with higher IgE also had more severe forms of eczema. In people with seasonal allergies, levels peak 4-6 weeks after pollen season [28, 41].
In over 1,000 people, those without allergies had the lowest average values (43.7 kU/L), followed by people with hidden allergies (213.8 kU/L) and asthma (626.6 kU/L) [27].
Hidden allergies are not accompanied by the typical symptoms. Apparently, even slightly elevated IgE might point to them.
A study on 562 children confirmed the connection between asthma and total IgE levels. It was a useful marker of lung sensitivity even in symptom-free children [42].
In 69 people with chronic hay fever, the average IgE levels were 378 kU/L – well above the normal range [35].
Food Allergies
Exposure to food allergens induces only a short-term increase in total IgE. It’s interesting that processed foods containing a particular allergen may cause 3-8 times higher levels compared with raw food allergens [37, 43].
Total IgE can’t detect food allergies, but tests that measure specific antibodies might do so [44].
The use of total IgE for allergy diagnosis comes with notable limitations we’ll discuss below (see “Limitations and Caveats”).
2) Parasitic Infections
As mentioned, the primary role of IgE is to detect and help eliminate worms and other parasites from our bodies. In the absence of allergic tendencies and symptoms, parasitic infection is the most probable cause of high IgE [45, 46].
We produce some parasite-specific IgE immunoglobulins, but they aren’t always detectable in people with infections. Additional tests from a feces sample or blood smear may be necessary to confirm the diagnosis [47, 48].
3) Th2 Dominance
We still have a lot to learn about the clinical relevance of Th1/Th2-dominance, but they do have some distinct immune features [49].
Th2 immune cells produce IL-4, which is the primary signal for B cells to make IgE. Thus, Th2-dominant people are more likely to have higher levels of these antibodies [50, 30].
4) Race and Location
People with African ancestry and those living in tropical areas naturally have higher IgE [51, 3].
5) Rare Diseases
Hyper IgE syndromes (HIES) are rare disorders accompanied by high blood IgE. People suffering from them experience frequent skin and respiratory infections due to impaired immunity [52].
Job’s syndrome is the most common type of HIES, which causes a range of bone and connective tissue abnormalities. IgE levels reach up to 2,000 kU/L, but they can drop (and even normalize) in adulthood [53].
A rare type of cancer called IgE multiple myeloma attacks plasma cells and causes increased production of these antibodies [54, 55].
Both conditions are uncommon, and there’s no reason to panic if your blood test revealed high IgE levels. A benign cause, such as allergen exposure is much more probable.
6) Genetics
According to a study on 877 Korean asthmatics, variants (SNPs) in the following genes might be associated with increased total IgE levels [56]:
7) Other
Other conditions or lifestyle factors that may elevate IgE include:
- Smoking [23, 27, 26]
- Alcohol consumption [31, 57, 58]
- Inflammatory bowel disease (IBD) [59, 60]
- Bacterial and viral infections [61, 28, 62]
- Lymphomas (lymphatic system cancers) [63, 60]
- Nephrotic syndrome (kidney disorder) [64, 65, 66]
As many different conditions can increase total IgE, it’s not suitable for diagnosing a particular disease or even allergies in general [27, 32].
Symptoms of Conditions That Increase IgE
There are no symptoms associated with high IgE levels per se. Instead, people with high IgE may only show symptoms of conditions discussed above. Your doctor will discuss your results with you. They may run additional tests to pinpoint the underlying cause of your high levels.
In most cases, the levels increase as a consequence of an allergic response with the symptoms such as [28, 37, 67]:
- Itchy skin and eyes
- Swelling
- Coughing and sneezing
- Nausea/vomiting
- Difficulty breathing
- Low blood pressure
If a parasitic infection spiked your IgE, it could manifest as [68, 69]:
- Sudden weight loss
- Anemia
- Digestive issues
- Fatigue
Associated Conditions
In over 1,000 older participants, high levels of IgE (≥267 kU/L) correlated with two times higher rates of cataracts, compared with average values (35-87 kU/L). Another similar study found 37% higher rates for increased IgE [70, 71].
Increased IgE was associated with 67-72% higher rates of type 2 diabetes in 2 studies with 1,800 adults. It correlated with increased blood glucose and insulin resistance, regardless of other risk factors [72, 73].
However, type 2 diabetic patients had lower IgE levels compared with controls (22.5 vs. 43.3 kU/L) in a Japanese study, while the average for type 1 diabetics was slightly higher (56.7 kU/L) [74].
Further clinical trials should examine the connection between IgE and diabetes. One thing is for sure: allergic diseases can raise the risk of diabetes (both types) and vice versa, which might explain the connection between total IgE and diabetes in some patients [75, 76, 77].
Potential Advantages
Although it usually signals an undesirable event, high IgE may be associated with lower cancer rate.
A meta-analysis of eight clinical trials (over 6,000 people) found significantly lower rates of brain tumors in people with high total IgE [78].
According to a comprehensive study on almost 38,000 individuals, elevated IgE has mixed correlation with different types of cancer. After removing other factors, higher IgE correlated with two times lower rates of blood cancers [79].
IgE antibodies can help your immune system target and destroy cancer cells. New IgE-based cancer drug candidates have shown promising results in preclinical trials. This kind of research belongs to a growing field of medicine called AllergoOncology [80, 14].
High IgE Levels? 5 Ways to Improve Immune Health
IgE levels are a marker of immune health. Low or high levels don’t necessarily indicate a problem if there are no symptoms or if your doctor tells you not to worry about it. Improving your IgE levels won’t necessarily cause improvement in immune balance, but it can be used as a biomarker for your immune health.
The following is a list of complementary approaches to improve immune health that may also balance high IgE levels. Though studies suggest various dietary and lifestyle factors may lower IgE levels, additional large-scale studies are needed.
Remember to talk to your doctor before making any major changes to your day-to-day routine.
1) Drug Treatment
Your doctor may prescribe immune-stabilizing drugs to manage your high IgE levels. Treatment will depend on the underlying disease and your overall symptoms.
For example, you may get an inhaled medication for asthma, creams for eczema, or nose sprays for hay fever.
These drugs may contain corticosteroids (to reduce swelling), antihistamines (to block histamine-triggered inflammation), or decongestants (to relieve nose stuffiness) [81].
Additionally, some IgE-targeted drugs include:
- Omalizumab, a biological drug that contains anti-IgE antibodies. These bind to IgE and remove it from the bloodstream, thus reducing allergic response. The FDA approved this drug for severe asthma and chronic hives (urticaria) [82, 83].
- Nedocromil sodium and disodium cromoglycate (cromolyn sodium), which belong to a group of drugs called mast cell stabilizers. They are available as inhalers, nasal sprays, and eye drops for asthma and seasonal allergies [84, 85, 86].
2) Avoid Allergen Exposure
If you are allergic to a particular food or animal, avoiding them will help prevent allergic reactions. You may also want to clean your house and workspace regularly to get rid of dust mites or mold.
3) Refrain From Smoking and Alcohol Consumption
Studies voice a clear connection between smoking and high IgE levels. Same goes for alcohol consumption, even in moderate amounts [23, 27, 57, 58].
Abstinence from smoking and alcohol consumption will help improve immunity and your overall health and wellbeing.
4) Increase Your Vitamin E Intake
A diet high in vitamin E may relieve allergic reactions and also lower IgE levels. Consume a variety of vitamin E-rich foods, such as [87, 88, 89]:
- Sunflower seeds
- Almonds
- Hazelnuts
- Spinach
- Broccoli
- Avocado
5) Consider Taking Supplements
A probiotic strain Bifidobacterium longum was able to reduce IgE and combat allergic reactions in multiple studies on mice and cells [90, 91, 92, 93].
Other strains that might help include B. breve, L. plantarum, and L. crispatus [94, 95, 96].
Besides probiotics, the following supplements may support the immune system and also combat IgE overproduction:
More research is needed to confirm the beneficial effects of these supplements on the immune system. Consult with your doctor before supplementing.
Low IgE Levels
Causes
IgE levels are a marker of immune health. Low or high levels don’t necessarily indicate a problem if there are no symptoms or if your doctor tells you not to worry about it.
There are no symptoms associated with low IgE levels per se. Instead, people with low IgE may only show symptoms of conditions discussed below. Your doctor will discuss your results with you. They may run additional tests to pinpoint the underlying cause of your low levels.
IgE levels can be quite low in the absence of allergic reactions and other triggers. They usually don’t indicate any disorder.
Selective IgE deficiency (IgE hypogammaglobulinemia) is a type of immunodeficiency with the levels of this antibody below the limit of detection: <2-2.5 kU/L. It may cause the following symptoms [102, 25]:
- Joint pain
- Chronic fatigue
- Coughing
- Difficulty breathing
If the levels of other antibodies (IgG, IgM, IgA) are low, common variable immunodeficiency (CVID) is the most probable cause. People with CVID have frequent respiratory and other infections that may lead to tissue damage [103, 104, 105].
The lack of antibodies and immunodeficiency can also occur due to [106, 33]:
- Drug treatment
- Kidney and gut disorders
- Cancer
- Severe burns
IgE is low in such cases but usually above 2 kU/L [103].
Ataxia-telangiectasia is a rare inherited immunodeficiency with low IgE levels while other antibodies are in the normal range. It causes “spider veins” and neurological disorders [107, 108].
Compared with high IgE, low IgE levels are a bit more specific lab marker, but they can’t confirm the exact type of immunodeficiency without additional tests [22, 33].
Associated Conditions
Immunodeficient people with extremely low IgE levels may be at a higher risk of infections, inflammatory diseases, and cancer [25, 108, 105].
In a study with over 1,000 people, those with IgE deficiency had higher rates of [102]:
- High blood pressure, 2-fold
- Heart disease, 3-fold
- Stroke, 6-fold
In more than 3,000 participants, IgE deficiency was associated with 43% higher rates of H. pylori infection. These patients also had more frequent stomach inflammation or gastritis (28%) and ulcers (47%) [109].
As mentioned above, high IgE may correlate with cataracts in the elderly. Same goes for low levels as those with ≤35 kU/L had 67% higher rates [70].
Takeaway
Immunoglobulin E (IgE) is an antibody that fights parasitic infections, microbes, and cancer cells. It is also involved in allergic reactions. This makes allergies and parasitic infections the two most common causes of increased total IgE (>150 kU/L).
Unlike specific tests, total IgE blood test has limited diagnostic value. Many different factors can cause high/low levels, but most healthy individuals will be in the range of 2-150 kU/L.
High IgE may be associated with higher rates of cataracts and diabetes and lower rates of brain and blood cancer. Complementary ways to improve immunity, which may also reduce IgE, include: increasing vitamin E intake, refraining from smoking and alcohol consumption, supplementing with probiotics, fish oil, and flavonoids.
Low or undetectable IgE (<2-2.5 kU/L) usually points to an immunodeficiency disorder that can cause frequent infections, gut disorders, and autoimmune diseases. Most importantly, make sure to discuss your high or low IgE levels with your doctor to check if they have any clinical relevance and if the underlying condition requires medical treatment.
