IgA deficiency

Related Terms

Allergic, allergic reaction, allergic response, anaphylaxis, antibiotics, antibodies, antibody, antigen, ataxia-telangiectasia, autoimmunity, B-cells, common variable immunodeficiency, CVID, glycoprotein, Ig, IgA, immune, immune defense system, immune system, immunocompromised, immunodeficiency, immunoglobulin, immunoglobulin A, infection, intravenous immunoglobulin, plasma cells, primary immunodeficiency, recurrent infections, serum.

Background

Selective immunoglobulin A (IgA) deficiency is a primary immune deficiency that occurs when individuals are unable to produce antibodies called immunoglobulin A.
Immunoglobulins (Ig), also called antibodies, play an essential role in the body's immune system. They detect and bind to foreign substances (like bacteria, viruses, fungi, or allergens) that enter the body. This signals other immune cells to destroy the foreign substance. The antibodies are present in the bloodstream or bound to the cell membranes of B-cells or plasma cells.
The IgA antibodies protect body surfaces (like the nose, airway passages, digestive tract, ears, eyes, saliva, tears, and vagina) that are frequently exposed to foreign organisms and substances from outside of the body.
The B-cells of selective IgA patients are unable to switch from making immunoglobulin M (IgM) to IgA. Healthy individuals express IgM on their B-cells. Once the B-cells come into contact with a foreign substance in the body, they become plasma cells and produce other antibodies, including IgA.
The amount of IgA produced is either significantly reduced or absent. Healthy adults have IgA levels that range from 100-400 milligrams/deciliter in the blood, while IgA deficient patients have IgA levels of 7 milligrams/deciliter or less.
The disorder is considered selective because all other antibodies (IgD, IgE, IgG, and IgM) are present at normal or increased levels. Other cells of the immune system, including the T-cells and phagocytic cells, are also produced at normal or increased levels. The T-cells and phagocytic cells are responsible for engulfing (destroying) the foreign substances that are bound to the antibodies.
Selective IgA deficiency appears to be an inherited disease that is passed down from parents to children. However, the exact genes involved remain unknown.
Most patients who have IgA deficiency experience no symptoms. Others may experience mild and recurrent infections of the mucosal surfaces, such as the nose, throat, lungs, and intestines. Ear infections, sinus infections, and pneumonia are most commonly associated with selective IgA deficiency. The frequency of these infections varies among patients.
Selective IgA deficiency is the most common primary immunodeficiency. Primary immunodeficiencies are disorders that occur because part of the body's immune system does not function properly. Unlike secondary immunodeficiencies, which are caused by factors (like viruses or chemotherapy) outside of the immune system, primary immunodeficiencies are caused by intrinsic or genetic defects of the immune system. In general, researchers estimate that selective IgA Deficiency occurs in about one out of 400-2,000 individuals worldwide. However, the incidence varies among people of different races and ethnicities. It occurs most frequently among people of European ancestry. Researchers estimate that one out of 500-700 people from this group develop the disorder.
There is currently no cure for selective IgA deficiency, although many patients do not require any medical treatment. Some patients need to take antibiotics to treat infections commonly associated with the disorder. For unknown reasons, some patients gradually develop normal levels of IgA without treatment.

Author information

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

Immune Deficiency Foundation. .
Lifespan. .
Michigan Immunodeficiency Foundation. .
National Institute of Allergy and Infectious Diseases. .
National Primary Immunodeficiency Diseases. .
Natural Standard: The Authority on Integrative Medicine. .

Causes

The exact cause of selective IgA deficiency remains unknown. In some patients, there appears to be a history of familial occurrence. This suggests the disorder may be inherited as either an autosomal dominant or recessive trait.
In order to inherit the disorder as an autosomal recessive disorder, one mutated gene from each parent must be inherited. Individuals who only have one mutated gene and do not express symptoms are called carriers. Carriers have a 50% chance of passing the abnormal gene to each of their children. If both parents are carriers, there is a 25% chance that each of their children will inherit the disorder and a 50% chance that each of their children will be a carrier.
In order to inherit the disorder as an autosomal dominant disorder, the child only needs to inherit one mutated gene. Individuals who have the disorder have a 50% chance of passing the disorder on to each of their children.
Selective IgA deficiency also occurs frequently in immediate relatives of patients who have a condition called common variable immunodeficiency (CVID).
Selective IgA deficiency has also been associated with ataxia-telangiectasia (degenerative disease that causes a loss of muscle control and reddening of the skin), frequent respiratory (lung) infections, and immunodeficiencies.

Symptoms

Most patients who have selective immunoglobulin A (IgA) deficiency experience no symptoms. Because the IgA antibodies protect body surfaces that are frequently exposed to foreign substances from outside of the body (like the nose, throat, lungs, and intestines), these patients may suffer from recurrent infections of these surfaces. Ear infections, sinus infections, and pneumonia are the most common infections that occur in symptomatic patients. However, most infections are generally mild.
Allergies, which range from mild to severe, are also common among patients. Allergic asthma and food allergies are especially common. Allergic asthma causes difficulty breathing, wheezing, and coughing, and may be less responsive to drug treatment than is typically expected in healthy patients. Food allergies may cause symptoms like abdominal cramps and diarrhea.

Diagnosis

General: A diagnosis of selective immunoglobulin A (IgA) deficiency can be made after low or absent levels of IgA are observed in a patient. Healthy adults typically have IgA levels of 100-400 milligrams/deciliter in the blood. The IgA will either be absent or below 7 milligrams/deciliter in patients who have selective IgA deficiency. Immunoglobulin G (IgG) and immunoglobulin M (IgM) will be present in normal levels.
Serum immunoelectrophoresis: A serum immunoelectrophoresis may be performed to determine whether a patient has selective IgA deficiency. During the procedure, a sample of the patient's blood is analyzed for the presence of immunoglobulins. The antibodies are separated from the blood sample during a process called electrophoresis. Based on the antigen-antibody interaction, it can be determined whether or not the patient has IgA antibodies.
Nephelometry: Nephelometry is another test that is often used to determine whether a patient has selective IgA deficiency. During the procedure, a sample of blood is taken from the patient. Anti-immunoglobulins are added to the blood sample. A medical instrument then measures the movement of particles in a substance that is caused by the interaction between immunoglobulins and anti-immunoglobulins. The test quickly and accurately measures the amount of IgM, IgG, and IgA in the patient's blood.

Treatment

General: There is currently no cure for selective IgA deficiency. While many patients do not require any medical treatment, some may need antibiotics to treat infections commonly associated with the disorder. For unknown reasons, some patients gradually develop normal levels of IgA without treatment.
Intravenous immunoglobulin (IVIG) therapy, which is often used to treat other primary immunodeficiencies, should not be used to treat selective IgA deficiency because some patients may develop antibodies to IgA. Once antibodies are created, severe reactions, including anaphylaxis (life-threatening allergic reaction), may occur if the patient receives IVIG.
Antibiotics: Antibiotics are prescribed to treat infections commonly associated with selective IgA deficiency. The type of medication, dose, and duration depend on the type and severity of infection, as well as the patient's overall health.
Commonly prescribed antibiotics for ear infections include amoxicillin (Trimox? or Biomox?) and Cefuroxime (Ceftin?, Kefurox?, or Zinacef?). Commonly prescribed antibiotics for sinus infections include amoxicillin (Amoxil?, Polymox?, or Trimox?) and trimethoprim/sulfamethoxazole, also called TMP/SMX (Bactrim?, Cotrim?, or Septra). Commonly prescribed antibiotics for pneumonia include azithromycin (Zithromax?), clarithromycin (Biaxin?), erythromycin (Erythrocin? or Ery-Tab?), and amoxicillin and clavulanate (Augmentin?).

Integrative therapies

Good scientific evidence:
Ginseng: Several studies suggest that ginseng can effectively enhance immune system function.
Avoid ginseng if known allergy to plants in the Araliaceae family. There has been a report of a serious life-threatening skin reaction, possibly caused by contaminants in the ginseng formulation.
Zinc: Zinc appears to be an essential trace element for the immune system, but research on the effect of zinc supplementation on immune function is scant and mostly focused on patients with specific diseases. Zinc gluconate appears to exert beneficial effects on immune cells, improving CD3 and CD4 counts (white blood cells that help coordinate the immune response) and increasing CD4/CD8 ratios in children. There are relatively few studies that examine zinc levels and the effects of zinc supplementation on the health of the elderly population. Further research is needed before a firm conclusion can be made.
Zinc is generally considered safe when taken at the recommended dosages. Avoid zinc chloride since studies have not been done on its safety or effectiveness. While zinc appears safe during pregnancy in amounts lower than the established upper intake level, caution should be used since studies cannot rule out the possibility of harm to the fetus.
Unclear or conflicting scientific evidence:
Arginine (L-arginine): Preliminary research results suggest that arginine supplementation may enhance the immune response elicited by the pneumococcal vaccine in older people. More studies are needed to confirm these results.
Avoid if allergic to arginine. Avoid with history of stroke, liver disease, or kidney disease. Avoid if pregnant or breastfeeding. Use cautiously if taking blood-thinning drugs (warfarin) and blood pressure drugs, or herbs or supplements with similar effects. Check blood potassium levels.
Astragalus: Astragalus has been suggested as an immune system stimulant in preliminary laboratory and animal research, and in traditional accounts. Reliable human studies are lacking. High quality human research is necessary before a firm conclusion can be drawn.
Avoid if allergic to astragalus, peas, or any related plants or with a history of Quillaja bark-induced asthma. Avoid with aspirin or aspirin products or herbs or supplements with similar effects. Avoid with inflammation (swelling) or fever, stroke, transplant, or autoimmune diseases (like HIV/AIDS). Stop use two weeks before surgery/dental/diagnostic procedures with a risk of bleeding and avoid use immediately after these procedures. Use cautiously with bleeding disorders, diabetes, high blood pressure, lipid disorders, or kidney disorders. Use cautiously with blood-thinners, blood sugar drugs, diuretics, or herbs and supplements with similar effects. Avoid if pregnant or breastfeeding.
Beta-carotene: Preliminary research of beta-carotene for immune system maintenance or stimulation shows mixed results. Further research is needed before a conclusion can be drawn.
Avoid if sensitive to beta-carotene, vitamin A, or any other ingredients in beta-carotene products.
Cat's claw: A few early studies suggest that cat's claw may boost the immune system. However, results from different studies have not agreed with each other. Therefore, further research is necessary in order to determine whether cat's claw can effectively enhance the immune response.
Avoid if allergic to Cat's claw, Uncaria plants, or plants in the Rubiaceae family, such as gardenia, coffee, or quinine. Avoid with a history of conditions affecting the immune system (such as AIDS, HIV, some types of cancer, multiple sclerosis, tuberculosis, rheumatoid arthritis, lupus). Use cautiously with bleeding disorders or history of stroke, or if taking drugs that may increase the risk of bleeding. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk, and do not use immediately after these procedures. Avoid if pregnant or breastfeeding. Cat's claw may be contaminated with other Uncaria species. Reports exist of the potentially toxic Texan grown plant Acacia gregii being substituted for cat's claw.
Copper: Copper is involved in the development of immune cells and immune function in the body. Severe copper deficiency appears to have adverse effects on immune function, although the exact mechanism is not clear.
Avoid if allergic/hypersensitive to copper. Avoid use of copper supplements during the early phase of recovery from diarrhea. Avoid with hypercupremia, occasionally observed in disease states including cutaneous leishmaniasis, sickle-cell disease, unipolar depression, breast cancer, epilepsy, measles, Down syndrome, and controlled fibrocalculous pancreatic diabetes (a unique form of secondary diabetes mellitus). Avoid with genetic disorders affecting copper metabolism such as Wilson's disease, Indian childhood cirrhosis, or idiopathic copper toxicosis. Avoid with HIV/AIDS. Use cautiously with water containing copper concentrations greater than 6 milligrams/liter. Use cautiously with anemia, arthralgia, and muscle pain. Use cautiously if taking oral contraceptives. Use cautiously if at risk for selenium deficiency. The recommended dietary allowance (RDA) is 1,000 micrograms for pregnant women. The RDA is 1,300 micrograms for breastfeeding women.
Echinacea: Echinacea has been studied alone and in combination preparations for immune system stimulation (including in patients receiving cancer chemotherapy). It remains unclear if there are clinically significant benefits. Additional studies are needed in this area before conclusions can be drawn regarding safety or effectiveness.
Avoid if allergic to plants in the Asteraceaeor Compositaefamilies (ragweed, chrysanthemums, marigolds, daisies). Avoid Echinacea injections. Avoid if history of liver disease or if taking amoxicillin. Avoid in organ transplant recipients. Use cautiously if driving or operating heavy machinery or if history of asthma, diabetes, conditions affecting the immune systems (like lupus, TB, AIDS-HIV), and rheumatologic conditions (rheumatoid arthritis). Avoid if pregnant or breastfeeding. Tinctures may contain large amounts of alcohol.
Gamma linolenic acid (GLA): Few clinical trials have investigated the effect of GLA on immune responses in healthy human subjects. Results from one randomized clinical trial suggest that GLA, as blackcurrant seed oil, may offer some benefits. Further well-designed clinical trials are required before definite conclusions can be made.
Use cautiously with drugs that increase the risk of bleeding like anticoagulants and anti-platelet drugs. Avoid if pregnant or breastfeeding.
Goldenseal: Goldenseal is sometimes suggested to be an immune system stimulant. However, there is little human or laboratory evidence in this area. More research is needed before a firm conclusion can be drawn.
Avoid if allergic or hypersensitive to goldenseal or any of its constituents, like berberine and hydrastine. Use cautiously with bleeding disorders, diabetes, or low blood sugar. Avoid if pregnant or breastfeeding.
Maitake mushroom: Animal and laboratory studies suggest that beta-glucan extracts from maitake may alter the immune system. However, no reliable studies in humans are available.
Maitake has not been studied thoroughly in humans, and its effects are not well known. Because it has been used historically as a food, it is thought that low doses may be safe. Avoid if allergic or hypersensitive to Grifola frondosa (maitake). Use cautiously with a history of low blood pressure, diabetes, or with drugs, herbs, or supplements that treat such conditions. Avoid if pregnant or breastfeeding.
Massage: Preliminary evidence suggests that massage therapy may preserve immune function. Further research is needed before a firm conclusion can be made.
Avoid with bleeding disorders, low platelet counts, or if taking blood-thinning medications (such as heparin or warfarin). Areas should not be massaged where there are fractures, weakened bones from osteoporosis or cancer, open/healing skin wounds, skin infections, recent surgery, or blood clots. Use cautiously if history of physical abuse or if pregnant or breastfeeding. Massage should not be used as a substitute for more proven therapies for medical conditions. Massage should not cause pain to the client.
Meditation: Preliminary research reports increased antibody response after meditation. Further study is needed to confirm these findings.
Use cautiously with underlying mental illnesses. People with psychiatric disorders should consult with their primary mental healthcare professional(s) before starting a program of meditation, and should explore how meditation may or may not fit in with their current treatment plan. Avoid with the risk of seizures. The practice of meditation should not delay the time to diagnosis or treatment with more proven techniques or therapies, and should not be used as the sole approach to illnesses.
Mistletoe: A few small trials found mistletoe to be promising as an immunostimulant in individuals with the common cold. Further research is needed to confirm these results.
Avoid if allergic or hypersensitive to mistletoe or to any of its constituents. Anaphylactic reactions (life threatening) have been described after injections of mistletoe. Avoid with acute highly febrile inflammatory disease, thyroid disorders, seizure disorders, or heart disease. Use cautiously with diabetes, glaucoma, or with cholinergics.
Probiotics: Lactobacillus in fermented milk, low-fat milk, or lactose-hydrolyzed low-fat milk may enhance immune function. Bifidobacterium may as well, including in the elderly. However, commercially produced yogurt may not yield similar benefits. There is some evidence that probiotics added during food preparation (e.g. waffles with Enterococcus faecium M-74 added) can enhance immune functioning. More studies are needed, particularly with yogurt, before a firm conclusion can be made.
Probiotics are generally considered safe and well-tolerated. Avoid if allergic or hypersensitive to probiotics. Use cautiously if lactose intolerant.
Vitamin A (retinol): Vitamin A deficiency may compromise immunity, but there is no clear evidence that additional vitamin A supplementation is beneficial for immune function in patients who are not vitamin A deficient.
Avoid if allergic or hypersensitive to vitamin A. Vitamin A toxicity can occur if taken at high dosages. Use cautiously with liver disease or alcoholism. Smokers who consume alcohol and beta-carotene may be at an increased risk for lung cancer or heart disease. Vitamin A appears safe in pregnant women if taken at recommended doses. Use cautiously if breastfeeding because the benefits or dangers to nursing infants are not clearly established.
Vitamin B6 (pyridoxine): Vitamin B6 is important for immune system function in older individuals. One study found that the amount of vitamin B6 required to reverse immune system impairments in elderly people was more than the current recommended dietary allowance (RDA). Well-designed clinical trials on vitamin B6 supplementation for this indication are needed before a recommendation can be made.
Some individuals seem to be particularly sensitive to vitamin B6 and may have problems at lower doses. Avoid excessive dosing. Vitamin B6 is likely safe when used orally in doses not exceeding the recommended dietary allowance (RDA). The RDA for pregnant women is 1.9mg per day. There is some concern that high-dose pyridoxine taken by a pregnant mother can cause seizures in a newborn. The RDA in breastfeeding women is 2 milligrams per day.
Vitamin E: Studies of the effects of vitamin E supplementation on immune system function have yielded mixed results. Further research is needed before a clear conclusion can be drawn.
Avoid if allergic or hypersensitive to vitamin E. For short periods of time, vitamin E supplementation is generally considered safe at doses up to 1,000 milligrams per day. Avoid doses higher than 1,000 milligrams a day. Avoid with retinitis pigmentosa (loss of peripheral vision). Use cautiously with bleeding disorders. The recommended dose of vitamin E for pregnant women of any age is 15 milligrams, and for breastfeeding women of any age is 19 milligrams. Use beyond this level in pregnant women is not recommended.
Fair negative scientific evidence:
DHEA (dehydroepiandrosterone): DHEA (dehydroepiandrosterone) is a naturally occurring hormone that is produced by the adrenal glands. Some textbooks and review articles have suggested that DHEA can stimulate the immune system. However, current scientific evidence does not support this claim.
Avoid if allergic to DHEA. Avoid with a history of seizures. Use cautiously with adrenal or thyroid disorders or if taking anticoagulants or drugs, herbs or supplements for diabetes, heart disease, seizure, or stroke. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk, and do not use immediately after these procedures. Avoid if pregnant or breastfeeding.
Lycopene: It has been proposed that lycopene and other carotenoids, such as beta-carotene, may stimulate the immune system. However, several studies of lycopene supplements and tomato juice intake in humans report no effects on the immune system.
Avoid if allergic to tomatoes or to lycopene. Due to a lack of conclusive data, avoid if pregnant or breastfeeding.

Prevention

Currently, there is no known method of prevention for selective immunoglobulin A (IgA) deficiency.
Vaccines, including the pneumococcal vaccine and pneumococcal 7-valent conjugate vaccine, may be administered to prevent infections that are commonly associated with the disorder.
Avoiding close contact with individuals who have contagious illnesses may help reduce the risk of acquiring infections.
Practicing good hygiene and regularly washing the hands with soap and water may help reduce the risk of acquiring infections.

Complications

Infections and allergic asthma, which are often associated with selective IgA deficiency, may be less responsive to antibiotics than is typically expected in healthy patients. Ear infections may cause complications such as hearing loss (short-term or long-term) or ruptured ear drum. Sinusitis may cause complications such as acute asthma, meningitis or vision loss. Pneumonia may cause complications like fluid in the lungs or abscesses (pus-filled cavities) in the lungs.
If IgA is completely absent, the patient may develop an autoimmune disorder. If this occurs, the patient's immune system creates antibodies to IgA. Once these antibodies are made, severe allergic reactions, including anaphylaxis (life-threatening allergic reaction) may occur if the patient receives a blood transfusion or blood products containing IgA (like intravenous immune globulin). This is because the immune cells mistake the IgA as an antigen (foreign substance), and they will attack the immunoglobulin.