- What is immunoglobulin A deficiency (IgAD)?
- Blood Test: Immunoglobulin A (IgA)
- Why It's Done
- The Procedure
- What to Expect
- Getting the Results
- Helping Your Child
- If You Have Questions
- What is Immunoglobulin A (IgA)? Blood Test & Normal Range
- Normal IgA Levels by Age
- Associations with Mortality
- IgA Genetics
- ATG13 and AMBRA1
- Selective IgA Deficiency
- Definition of Selective IgA Deficiency
- Clinical Features of Selective IgA Deficiency
- Diagnosis of Selective IgA Deficiency
- Inheritance of Selective IgA Deficiency
- Treatment of Selective IgA Deficiency
- Expectations for Patients with Selective IgA Deficiency
- Blood Test: Immunoglobulins (IgA, IgG, IgM)
- What Is an Immunoglobulin Test?
What is immunoglobulin A deficiency (IgAD)?
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Blood Test: Immunoglobulin A (IgA)
An IgA test measures the blood level of immunoglobulin A, one of the most common antibodies in the body. Antibodies are proteins made by the immune system to fight bacteria, viruses, and toxins.
IgA is found in high concentrations in the body's mucous membranes, particularly the respiratory passages and gastrointestinal tract, as well as in saliva and tears.
IgA also plays a role in allergic reactions. IgA levels also may be high in autoimmune conditions, disorders in which the body mistakenly makes antibodies against healthy tissues.
Why It's Done
An IgA test can help doctors diagnose problems with the immune system, intestines, and kidneys. It may be done in kids who have recurrent infections.
It's also used to evaluate autoimmune conditions, such as rheumatoid arthritis, lupus, and celiac disease.
Kids born with low levels of IgA — or none at all — are at increased risk of developing an autoimmune condition, infections, asthma, and allergies.
Your doctor will tell you if any special preparations are required before this test. On the day of the test, having your child wear a T-shirt or short-sleeved shirt can make things easier for your child and the technician who will be drawing the blood.
A health professional will usually draw the blood from a vein. For an infant, the blood may be obtained by puncturing the heel with a small needle (lancet).
If the blood is being drawn from a vein, the skin surface is cleaned with antiseptic, and an elastic band (tourniquet) is placed around the upper arm to apply pressure and cause the veins to swell with blood.
A needle is inserted into a vein (usually in the arm inside of the elbow or on the back of the hand) and blood is withdrawn and collected in a vial or syringe.
After the procedure, the elastic band is removed. Once the blood has been collected, the needle is removed and the area is covered with cotton or a bandage to stop the bleeding. Collecting blood for this test will only take a few minutes.
What to Expect
Either method (heel or vein withdrawal) of collecting a sample of blood is only temporarily uncomfortable and can feel a quick pinprick. Afterward, there may be some mild bruising, which should go away in a few days.
Getting the Results
The blood sample will be processed by a machine. The results are commonly available within a day or two. If results suggest an abnormality, the doctor may perform further tests.
This test is considered a safe procedure. However, as with many medical tests, some problems can occur with having blood drawn, :
- fainting or feeling lightheaded
- hematoma (blood accumulating under the skin causing a lump or bruise)
- pain associated with multiple punctures to locate a vein
Helping Your Child
Having a blood test is relatively painless. Still, many children are afraid of needles. Explaining the test in terms your child might understand can help ease some of the fear.
Allow your child to ask the technician any questions he or she might have. Tell your child to try to relax during the procedure, as tense muscles can make it harder and more painful to draw blood. It also may help for your child to look away when the needle is being inserted into the skin.
If You Have Questions
If you have questions about the IgA test, speak with your doctor.
What is Immunoglobulin A (IgA)? Blood Test & Normal Range
Immunoglobulin A is the first line of defense against harmful microbes, but it also maintains your immune tolerance. It is the dominant antibody in your gut, respiratory mucus, breast milk, and other secreted fluids. Read on to find out what the IgA blood test can tell you about your health and whether your levels are normal.
Immunoglobulin A (IgA) is a type of antibody. Antibodies are proteins of the immune system that bind to and neutralize pathogens such as bacteria and viruses .
IgA is one of the five immunoglobulin classes (in addition to IgG, IgM, IgD, and IgE) .
In the human body, more IgA is produced per day than all other antibodies combined [2, 3, 1].
IgA is produced by white blood cells (B cells) and is then transported into fluids secreted by mucosal cells. This IgA is called the secretory IgA. Secretory IgA is the dominant antibody in [1, 2]:
- Gut mucus (intestinal barrier)
- Respiratory mucus
- Urogenital mucus
IgA is also the second most prevalent antibody in the blood (after IgG) [2, 4].
Circulating IgA is in monomeric form, whereas secretory IgA, in the mucosal secretions of respiratory, intestinal, and genitourinary systems, is dimeric (in the form of two joined IgA monomers) .
Mucosal barriers (where IgA is present) separate the interior of the body from the outside world. At these sites, IgA maintains a balanced immune response. It defends against harmful microbes but also prevents reactions against good bacteria and environmental proteins (such as food antigens) .
IgA has many important functions:
- It is the first line of defense against harmful microbes [1, 3].
- It removes microbes that have breached the epithelial barrier (such as the intestinal barrier) .
- It can neutralize toxins and viruses [1, 7, 2].
- It shapes the composition of the gut microbiota [3, 1].
- It neutralizes inflammatory products from microbes [8, 9].
- IgA from mother’s milk helps program the infant immune system by regulating their microbiota and protecting them from pathogens .
- It helps maintain immune tolerance at mucosal barriers by dampening immune responses against good bacteria and food components .
Normal IgA Levels by Age
Normal IgA levels vary slightly depending on the laboratory used to test them. They gradually increase with age and weight in children until they reach stable levels in adults. Blood IgA levels are higher in males than in females .
These are the approximate values for IgA depending on age:
- 0-1 years: 1-83 mg/dL
- 1-5 years: 20-152 mg/dL
- 5-10 years: 33-274 mg/dL
- 10-17 years: 42-378 mg/dL
- Older than 18 years: 60-400 mg/dL
Associations with Mortality
Both low and high IgA levels are associated with higher mortality.
In 4,255 Vietnam-era war veterans, higher IgA levels were associated with a 2-fold increased risk of dying from both all-causes and infectious diseases .
In people aged 90 – 99 years, higher IgA levels were associated with higher mortality .
Similarly, in 8-year-olds, high IgA levels (>400 mg/dl) were associated with higher mortality. IgA levels were related to cancer mortality in males .
On the other hand, higher IgA was associated with a decreased risk of death from cancer, specifically non-lung cancer, as well as from respiratory disease .
Severe IgA deficiency was associated with higher mortality in the first 10 – 15 years after diagnosis .
High and low IgA levels can have many underlying causes. Thus, the health conditions triggering abnormal IgA levels are more ly to impact a person’s risk of dying than IgA levels themselves. Additional studies should give us more clues about this link.
If you’re not a big fan of genetics, skip straight to our other posts about IgA in the next section.
The following genes have been associated with IgA levels and IgA deficiency:
A study in 9,617 subjects showed that IgA levels were associated with the rs13300483 variant in the TNFSF8 gene .
TNFSF8 is a cytokine that induces immune cell (T-cell) production.
This variant has also been associated with IBD .
IFIH functions as a sensor for viral infections .
Variant rs1990760 is associated with IgA deficiency (430 cases and 1,090 controls) .
This variant has also been associated with type 1 diabetes and lupus .
Another rs35667974 variant in the same gene was also associated with IgA deficiency (1,635 patients and 4,852 controls) .
CLEC16A is a protein of unknown function found on white blood cells.
The rs6498142 variant in this gene is associated with IgA deficiency .
The rs34069391 variant is protective against IgA deficiency (1,635 patients with IgA deficiency and 4,852 controls) .
This gene has also been associated with type 1 diabetes, lupus, celiac disease, and multiple sclerosis [22, 23, 24, 25].
The rs11299600 variant is protective against IgA deficiency .
This gene of unknown function has been associated with cancer .
ATG13 and AMBRA1
The rs4565870 variant was associated with IgA deficiency .
This variant could affect either ATG13, AMBRA1, or both genes (still unknown).
Both ATG13 and AMBRA1 are involved in the recycling of cell components (autophagy) [26, 27].
The rs7773987 variant was associated with IgA deficiency .
This gene plays an important role in brain development. It has been associated with schizophrenia, autism, depression, and multiple sclerosis [28, 29, 30, 31].
HS1.2 is an enhancer region important for immunoglobulin production .
HS1.21 increases the risk, while HS1.22 and HS1.2*4 decrease the risk of IgA deficiency (88 IgA deficient patients and 101 controls) .
HS1.2 has been associated with psoriasis and rheumatoid arthritis [34, 35].
HLA-DQA1 plays an important role in the immune system. It helps distinguish viruses and bacteria from the body’s own proteins.
The rs116041786 variant was associated with IgA deficiency (1,635 patients with IgA deficiency and 4,852 controls) .
This gene has been associated with celiac and Graves’ disease [36, 37].
Selective IgA Deficiency
Individuals with Selective IgA Deficiency lack IgA, but usually have normal amounts of the other types of immunoglobulins. Selective IgA Deficiency is relatively common in Caucasians. Many affected people have no illness as a result. Others may develop a variety of significant clinical problems.
Definition of Selective IgA Deficiency
Selective IgA Deficiency is defined as a primary immunodeficiency characterized by an undetectable level of immunoglobulin A (IgA) in the blood and secretions but no other immunoglobulin deficiencies.
There are five types (classes) of immunoglobulins or antibodies in the blood: IgG, IgA, IgM, IgD and IgE. IgG is present in the largest amount, followed by IgM and IgA. IgD is much lower, and IgE is present in only minute amounts.
IgM and IgG mainly protect us from infections inside our body tissues, organs and blood.
While IgA is present in the blood, most of the IgA in the body is in the secretions of the mucosal surfaces, including tears, saliva, colostrum, genital, respiratory and gastrointestinal secretions.
The IgA antibodies in the secretions play a major role in protecting us from infections in these areas. IgG and IgM are also found in secretions but not in nearly the same amount as IgA.
IgA present in these secretions is also termed secretory IgA.
If human mucosal surfaces were spread out flat, they would cover an area equal to one and a half tennis courts, so the importance of IgA in protecting mucosal surfaces cannot be overstated.
Secretory IgA has some differences compared to the IgA present in the blood. Secretory IgA is made of two IgA antibody molecules joined together by a protein called the J chain (“J” for “joining”). (See chapter titled “The Immune System and Primary Immunodeficiency Diseases.
”) In order for this unit to be secreted, it must also be attached to another protein called the secretory piece.
Therefore, the final secretory IgA unit that protects the mucosal surfaces is actually composed of two IgA molecules joined by the J chain and attached to the secretory piece.
Although individuals with Selective IgA Deficiency do not produce IgA (or produce only extremely small amounts), they do make all the other immunoglobulin classes; hence the term Selective IgA Deficiency. Furthermore, the functions of their T-lymphocytes, phagocytic cells and complement systems are all normal.
Click Here to connect with other individuals living with Selective IgA Deficiency on . Join Selective IgA Deficiency: An Official IDF Group.
Clinical Features of Selective IgA Deficiency
Selective IgA Deficiency is one of the most common primary immunodeficiency diseases. Studies have indicated that as many as one in every 500 Caucasian people has Selective IgA Deficiency. The rate of occurrence may be different in other ethnic groups.
Many of these individuals appear healthy, or have relatively mild illnesses, and are generally not sick enough to be seen by a doctor and may never be discovered to have IgA deficiency.
On the other hand, there are individuals with Selective IgA Deficiency who have significant illnesses.
Currently, it is not understood why some individuals with IgA deficiency have almost no illness while others are very sick.
Also, it is not known precisely what percent of individuals with IgA deficiency will eventually develop complications; estimates range from 25% to 50%. Some patients with IgA deficiency also have very low levels of certain IgG subclasses (usually IgG2 and/or IgG4).
That may be part of the explanation of why some patients with IgA deficiency are more susceptible to infection than others, but this is not the case for all patients with IgA deficiency who develop complications or for those who have low IgG2 and/or IgG4 in addition to absent IgA.
A common problem in Selective IgA Deficiency is susceptibility to infections. This is seen in about half of the patients with IgA deficiency that come to medical attention. Recurrent ear infections, sinusitis, bronchitis and pneumonia are the most common infections seen in patients with Selective IgA Deficiency.
Some patients also have gastrointestinal infections and chronic diarrhea. The occurrence of these kinds of infections is easy to understand since IgA protects mucosal surfaces. These infections may become chronic. Furthermore, the infection may not completely clear with treatment, and patients may have to remain on antibiotics for longer than usual.
Sometimes long-term antibiotic prophylaxis is needed to keep them free from infections.
A second major problem in IgA deficiency is the occurrence of autoimmune diseases. These are found in about 25% to 33% of patients who seek medical help.
In autoimmune diseases, individuals produce antibodies or T-lymphocytes, which react with their own tissues with resulting inflammation and damage.
Some of the more frequent autoimmune diseases associated with IgA deficiency are: rheumatoid arthritis, systemic lupus erythematosus and immune thrombocytopenic purpura. Other kinds of autoimmune disease may affect the endocrine system and/or the gastrointestinal system.
Allergies may also be more common among individuals with Selective IgA Deficiency than among the general population. These occur in about 10-15% of these patients. The types of allergies vary. Asthma is one of the common allergic diseases that occurs with Selective IgA Deficiency.
It has been suggested that asthma may be more severe, and less responsive to therapy, in individuals with IgA deficiency than it is in people with normal IgA. Food allergy may also be associated with IgA deficiency.
It is not certain whether there is an increased incidence of allergic rhinitis (hay fever) or eczema in Selective IgA Deficiency.
The causes of Selective IgA Deficiency are unknown. It is ly that there are a variety of causes, and this explains why the symptoms or health problems may vary from individual to individual.
Low but detectable serum IgA (sometimes called partial IgA deficiency), undetectable serum IgA, is also relatively common. Similarly, most people with low serum IgA have no apparent illness. Some people with low serum IgA have a clinical course very similar to people with Common Variable Immune Deficiency (CVID). (See chapter titled “Common Variable Immune Deficiency.”)
Diagnosis of Selective IgA Deficiency
The diagnosis of Selective IgA Deficiency is usually suspected because of chronic or recurrent infections, autoimmune diseases, chronic diarrhea or some combination of these problems.
Other patients are identified when immunoglobulins are ordered for some non-immunologic problem.
The diagnosis is established when blood tests demonstrate undetectable levels of IgA (reported usually as < 5-7 mg/dL), with normal levels of the other major classes of immunoglobulins (IgG and IgM).
Occasionally, some patients with IgA deficiency may also have low levels of IgG2 and/or IgG4 and associated antibody deficiency. B-cell numbers and the numbers and functions of T-lymphocytes are normal. (See chapters titled “Specific Antibody Deficiency” and “IgG Subclass Deficiency.”)
Several other tests that may be important include a complete blood count, measurement of lung function and urinalysis. Other tests that may be obtained include measures of thyroid function, kidney function, nutrient absorption in the GI tract and antibodies directed against the body’s own tissues (autoantibodies).
Inheritance of Selective IgA Deficiency
Familial inheritance of Selective IgA Deficiency occurs in approximately 20% of cases and, within families, Selective IgA Deficiency, CVID and Transient Hypogammaglobulinemia of Infancy may be associated. If family members are suspected of having immune problems, immunoglobulin levels may be obtained to determine a familial pattern of disease.
Treatment of Selective IgA Deficiency
It is not currently possible to replace IgA in patients with IgA deficiency, although research toward purification of human IgA is ongoing. However, it remains to be seen if replacement of IgA by any route (IV, oral or topical) will be beneficial for humans with IgA deficiency, in part because IgA in the serum, un IgG, does not remain in the circulation for very long.
Treatment of the complications associated with Selective IgA Deficiency should be directed toward the particular problem. For example, patients with chronic or recurrent infections need appropriate antibiotics.
Ideally, antibiotic therapy should be targeted at the specific organism causing the infection.
Unfortunately, it is not always possible to identify these organisms and their antibiotic sensitivities precisely, and the use of broad-spectrum antibiotics may be necessary.
Certain patients who have chronic sinusitis or chronic bronchitis may need to stay on long-term preventive antibiotic therapy (antibiotic prophylaxis). It is important that the doctor and the patient communicate closely so that appropriate decisions can be made regarding therapy.
As mentioned above, some patients with IgA deficiency also have IgG2 and/or IgG4 subclass deficiency and/or a deficiency of antibody production. However, these laboratory findings do not always predict a greater frequency or severity of infections.
If a patient has many infections, poor vaccine antibody responses and fails other preventive treatment (for example, antibiotic prophylaxis) a trial of immunoglobulin replacement therapy may be considered.
(See chapter titled “Immunoglobulin Therapy and Other Medical Therapies for Antibody Deficiencies.”)
Patients with Selective IgA Deficiency are often considered to be at increased risk of life-threatening allergic reactions, or anaphylaxis when they receive blood products, including intravenous immunoglobulin (IVIG), that contain some IgA. This is thought to be due to IgG (or possibly IgE) anti-IgA antibodies, which may be found in some IgA-deficient individuals. However, most patients with IgA deficiency do not have adverse reactions to blood products or IVIG.
There is no consensus among experts in this field regarding the exact magnitude of the risk of these types of reactions in patients with IgA deficiency, or the need for caution or measurement of anti-IgA antibodies before administration of blood or IVIG. However, these reactions are very rare overall. Furthermore, anaphylaxis has not been reported in patients with IgA deficiency receiving subcutaneous immunoglobulin infusions.
There are a variety of therapies for the treatment of autoimmune diseases. Anti-inflammatory drugs, such as aspirin, ibuprofen or naproxen, are used in many diseases that cause joint inflammation.
Steroids may also be helpful in a variety of autoimmune diseases. Many biological drugs (monoclonal antibodies) have also been developed to treat inflammatory and autoimmune diseases.
If autoimmune disease results in an abnormality of the endocrine system, replacement therapy with hormones may be necessary.
Treatment of the allergies associated with IgA deficiency is similar to treatment of allergies in general. It is not known whether immunotherapy (allergy shots) is helpful in the allergies associated with Selective IgA Deficiency; although there is no evidence of any increased risk associated with this therapy in these patients.
The most important aspect of therapy in IgA deficiency is close communication between the patient (and/or the patient’s family) and the physician so that problems can be recognized and treated as soon as they arise.
Expectations for Patients with Selective IgA Deficiency
Although Selective IgA Deficiency is usually one of the milder forms of immunodeficiency, it may result in severe disease in some people. Therefore, it is difficult to predict the long-term outcome in an individual patient with Selective IgA Deficiency.
Excerpted from the IDF Patient & Family Handbook for Primary Immunodeficiency Diseases FIFTH EDITION. Copyright 2013 by Immune Deficiency Foundation, USA.
This page contains general medical information which cannot be applied safely to any individual case. Medical knowledge and practice can change rapidly.
Therefore, this page should not be used as a substitute for professional medical advice.
Blood Test: Immunoglobulins (IgA, IgG, IgM)
An immunoglobulin test measures the level of certain immunoglobulins, or antibodies, in the blood. Antibodies are proteins made by the immune system to fight antigens, such as bacteria, viruses, and toxins.
The body makes different immunoglobulins to combat different antigens. For example, the antibody for chickenpox isn't the same as the antibody for mononucleosis. Sometimes, the body may even mistakenly make antibodies against itself, treating healthy organs and tissues foreign invaders. This is called an autoimmune disease.
The five subclasses of antibodies are:
- Immunoglobulin A (IgA), which is found in high concentrations in the mucous membranes, particularly those lining the respiratory passages and gastrointestinal tract, as well as in saliva and tears.
- Immunoglobulin G (IgG), the most abundant type of antibody, is found in all body fluids and protects against bacterial and viral infections.
- Immunoglobulin M (IgM), which is found mainly in the blood and lymph fluid, is the first antibody to be made by the body to fight a new infection.
- Immunoglobulin E (IgE), which is associated mainly with allergic reactions (when the immune system overreacts to environmental antigens such as pollen or pet dander). It is found in the lungs, skin, and mucous membranes.
- Immunoglobulin D (IgD), which exists in small amounts in the blood, is the least understood antibody.
IgA, IgG, and IgM are often measured together. That way, they can give doctors important information about immune system functioning, especially relating to infection or autoimmune disease.
What Is an Immunoglobulin Test?
This test checks the amount of certain antibodies called immunoglobulins in your body.
Antibodies are proteins that your immune cells make to fight off bacteria, viruses, and other harmful invaders. The immunoglobulin test can show whether there's a problem with your immune system.
Some conditions cause your body to make too many or too few immunoglobulins.
Having too few immunoglobulins in your blood gives you a greater chance of getting infections. Having too many could mean you have allergies or an overactive immune system.
Your body makes a few different types of immunoglobulin antibodies, including these:
Immunoglobulin A: IgA antibodies are found in the mucous membranes of the lungs, sinuses, stomach, and intestines. They're also in fluids these membranes produce, saliva and tears, as well as in the blood.
Immunoglobulin G: IgG is the most common type of antibody in your blood and other body fluids. These antibodies protect you against infection by “remembering” which germs you've been exposed to before.
If those germs come back, your immune system knows to attack them. Your doctor can test for IgG to figure out whether you've been infected by certain kinds of bacteria or virus.
Immunoglobulin M: Your body makes IgM antibodies when you are first infected with new bacteria or other germs.
They are your body's first line of defense against infections. When your body senses an invader, your IgM level will rise for a short time. It will then begin to drop as your IgG level kicks in and increases to protect you long-term.
Immunoglobulin E: Your body makes IgE antibodies when it overreacts to substances that aren't harmful, such as pollen or pet dander. Your doctor will ly measure your IgE levels if you have a blood test to check for allergies.
Your doctor might order an immunoglobulin test if you get a lot of infections — especially infections of the sinuses, lungs, stomach, or intestines.
She may also order the test if you have:
Doctors often measure IgA, IgG, and IgM together to get a snapshot of your immune function. A lab tech will usually take a sample of your blood by inserting a needle into a vein in your arm. The blood collects into a tube or vial.
Another way to do this test is with a sample of what’s called cerebrospinal fluid (CSF).
CSF surrounds your brain and spinal cord. The doctor will take a sample of this fluid with a lumbar puncture (often called a “spinal tap”).
For this, you go to an outpatient facility or a hospital. A technician will give you a shot in your back to help numb any pain.
You will ly lie on your side with your knees pulled up to your chest, or you sit on a table. The technician inserts a hollow needle between two vertebrae in your lower spine and removes a small amount of fluid so it can be tested.
The sample will be sent to a lab for testing. This might take a few days.
Depending on your results, the doctor might need to do other tests, such as a:
If your immunoglobulin level is high, it might be caused by:
Low levels of immunoglobulins mean your immune system isn't working as well as it should. This can be caused by:
Just because your immunoglobulin level is high or low doesn't mean you have one of these conditions.
Each person's test can differ the method the lab uses to check the results. Talk to your doctor about your test results, and find out what you should do next.
American Association for Clinical Chemistry: “Quantitative Immunoglobulins: At a Glance,” “Quantitative Immunoglobulins: Test Sample,” “Quantitative Immunoglobulins: The Test.”
Mayo Clinic: “Lumbar puncture (spinal tap): What you can expect.”
Nemours Foundation: “Blood Test: Immunoglobulins (IgA, IgG, IgM).”
Pagana, Kathleen Deska. Mosby's Diagnostic and Laboratory Test Reference, 2016.
University of Rochester Medical Center: “Quantitative Immunoglobulins.”
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