IgA Deficiency

What Is Immunoglobulin A?

Immunoglobulin A is also known as IgA, which is an antibody found in our blood. Antibodies are substances created by the immune system that recognizes and fights off infectious agents. IgA is a type of antibody that helps fight infections in the gastrointestinal tract, respiratory tract, mucus membrane, and blood. There are five different types of antibodies our body creates, which are IgE, IgA, IgD, IgG, and IgM. Each antibody has a different function within our bodies. 

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IgA antibodies are mainly located in the linings of the mucus membrane, gastrointestinal tract, and respiratory tract. They are also found in saliva, tears, and breast milk. IgA is the first line of defense against foreign substances that your body encounters. It neutralizes bacterial toxins and viruses both intracellularly and extracellularly by preventing viral and bacterial adhesion to epithelial cells. IgA antibodies work to protect the body and fight infections in the areas of the body where they are found. 

There are two types of IgA in our bodies: 

• IgA1, found in serum
• IgA2, also known as secretory IgA, found in mucus secretions

What Is IgA Deficiency?

Apart from IgA, there are other antibodies responsible for protecting us against infections, such as the IgG and IgM antibodies. IgA deficiency (also known as selective IgA deficiency) is when a person has low or nonexistent levels of IgA in their blood. It is considered a primary immunodeficiency.

Most patients suffering from immunoglobulin A deficiency have normal levels of other immunoglobulins that protect them from infections and help them stay healthy. This is why IgA deficiency is not always serious, and in most patients, it only causes minor gastrointestinal or respiratory infections.

Who Can Get IgA Deficiency?

Several different factors can contribute to low IgA levels in the blood, including:

Health Conditions:

Certain health conditions are responsible for causing low IgA levels. For example, poor sleep, gut disorders, exhaustion, allergies, and chronic stress can lower IgA levels in saliva.

Autoimmune diseases (when your immune system attacks its own tissues and organs) may also decrease IgA levels. Autoimmune diseases that may decrease IgA levels include:

• Rheumatoid arthritis
• Inflammatory bowel disease
• Lupus
• Celiac disease 

Inheritance:

Hereditary factors also play a role in causing low IgA levels. Although rare, those with a family history of IgA deficiency are more likely to develop low IgA levels. 

Medications:

Some medications also lead to low IgA levels, including:

• Thyroxine
• Sulfasalazine
• Phenytoin 
• Valproic acid
• Cyclosporin
• D-Penicillamine
• Captopril
• Chemotherapy drugs

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IgA Deficiency Effects

IgA deficiency can become serious and can cause a life-threatening condition known as anaphylaxis (a severe allergic reaction). But most of the time, it only increases the susceptibility to infection and sickness. 

For example, people with selective IgA deficiency may frequently suffer from infections of the respiratory system, gastrointestinal tract, and lungs. This is because IgA is mainly located in the blood and the mucus secretions of these organs and the lack of IgA in these areas increases the risk of infection as there are little to no antibodies to fight off infections.

Common gastrointestinal infections associated with immunoglobulin A deficiency can include:

• Giardiasis (a diarrheal disorder)
• Inflammatory bowel disease (chronic inflammation in the gastrointestinal tract)
• Nodular lymphoid hyperplasia (presence of small nodules on the stomach, large intestine, or rectum)
• Celiac disease (a digestive and autoimmune disorder that causes an immune reaction in the small intestine from eating gluten)

Patients with immunoglobulin A deficiency may also experience autoimmune disorders and allergic reactions. 

Signs and Symptoms

The clinical manifestation of immunoglobulin A deficiency is a predisposition towards recurrent infections, which the body defends by antibody response. More commonly, IgA deficiency may often be asymptomatic (no apparent signs or symptoms). If symptoms are present, they may vary from patient to patient, for example: 

• Some patients experience no illness and appear healthy.
• Some patients encounter slight to moderate infections.
• Some patients may become more prone to allergic reactions or asthma from immunoglobulin A deficiency.
• Some patients encounter frequent infections and may need long-term antibiotic treatment.
• Some patients may need external IgA therapy in the form of IVIG treatment.

Symptoms of IgA Deficiency can include:

• Fatigue or unusual tiredness (the most common and frequent symptom)
• Susceptibility to infections
• Pneumonia and respiratory infections
• Gastrointestinal inflammation
• Bacterial infections
• Conjunctivitis
• Chronic diarrhea
• Mouth infection
• Bronchitis
• Otitis media
• Allergies
• Asthma

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Diagnosis

The diagnosis of IgA deficiency is mainly made by evaluating frequent and recurring infections or symptoms associated with immunoglobulin A deficiency.

Blood tests are also available to diagnose selective IgA deficiency. A blood test indicating low levels of IgA with normal levels of other immunoglobulins (IgG, IgM, IgE, and IgD) can be interpreted as immunoglobulin A deficiency.

Some patients with selective IgA deficiency may have slightly lower levels of other antibodies in their blood, but the condition may vary from patient to patient.

Complications

Complications from immunoglobulin A deficiency occur when the problems associated with this condition become severe and life-threatening.

IgA deficiency may lead to asthma and allergies. An anaphylactic reaction (severe allergic reaction) is the most common complication. People with IgA deficiency may develop sensitivity to blood products, and this can increase the chances of an anaphylactic reaction.

Severe complications that can require immediate medical attention include:

• Anaphylactic reactions on receiving blood products like IVIG (intravenous immunoglobulin)
• Autoimmune disorders like rheumatoid arthritis, celiac disease, systemic lupus erythematosus, or inflammatory bowel disease
• Severe otitis media (ear infection)
• Malabsorption syndrome
• Growth retardation
• Chronic diarrhea
• Bronchiectasis

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Treatment Options

There is no permanent cure for IgA deficiency; however, some measures can be taken to improve IgA levels, such as boosting the immune system to reduce the risk of encountering infections. Symptoms and conditions may vary from patient to patient, so the treatment plan may differ accordingly.  

Patients with immunoglobulin A deficiency encountering frequent infections may need to use antibiotics. Those who constantly suffer from chronic bronchitis or sinusitis may need to stay on long-term preventative antibiotic treatment. If the condition gets worse, the patient may be treated with immunoglobulin replacement therapy (IRT), which works by administering IgA externally in the form of IVIG therapy.  

Therefore, the treatment of immunoglobulin A deficiency mainly focuses on treating problems associated with IgA deficiency along with some ways to improve IgA levels, but a permanent cure is still not available. 

Natural ways to increase IgA levels include: 

Dietary Modifications: 

Vitamin A has been proven to increase IgA levels. Vitamin A is necessary for the release and transport of IgA across the mucosa, therefore, incorporating vitamin A into the diet can potentially improve IgA levels. 

Another dietary recommendation includes fasting, especially if overweight or obese. Fasting can increase IgA levels.

Lifestyle Changes: 

Since chronic stress can lead to IgA deficiency, managing stress in such patients is of the utmost importance if they have low IgA levels from chronic stress.

It is also recommended that smokers quit using cigarettes and tobacco products, as they can lower IgA levels. 

Prognosis

The life expectancy and prognosis of immunoglobulin A deficiency may rely upon the individual’s immunodeficiency, its type, and severity. Those who get many severe infections will have a worse outlook than those who don’t get as many infections. Research shows that IRT combined with antibiotic therapy for infections dramatically improves the outlook of IgA deficiency. 

REFERENCES:

1. Selective IgA Deficiency Symptoms, Diagnosis & Treatment | AAAAI. Aaaai.org. https://www.aaaai.org/Conditions-Treatments/primary-immunodeficiency-disease/selective-iga-deficiency. Published 2022. Accessed March 18, 2022.
2. Immunoglobulin A Deficiency. Hopkinsmedicine.org. https://www.hopkinsmedicine.org/health/conditions-and-diseases/immunoglobulin-a-deficiency#:~:text=Having%20an%20IgA%20deficiency%20means,part%20in%20asthma%20and%20allergies. Published 2022. Accessed March 18, 2022.
3. Selective IgA deficiency – Symptoms and causes. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/selective-iga-deficiency/symptoms-causes/syc-20362236. Published 2022. Accessed March 18, 2022.
4. Selective IgA Deficiency | Immune Deficiency Foundation. Primaryimmune.org. https://primaryimmune.org/about-primary-immunodeficiencies/specific-disease-types/selective-iga-deficiency. Published 2022. Accessed March 18, 2022.