Hypogammaglobulinemia Explained

Medically Reviewed By Meredith Goodwin, MD, FAAFP
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Hypogammaglobulinemia results from low levels of immunoglobulins or antibodies in your blood. It causes issues with your immune system. The immune system typically produces antibodies to protect against infectious agents and unknown bodies. However, some immune systems may not produce enough antibodies. People with these immune systems are prone to chronic infections and allergic reactions. Some people may have immunodeficiencies and hypogammaglobulinemia.

This article discusses hypogammaglobulinemia symptoms, causes, treatment options, complications, and outlook.

What is hypogammaglobulinemia?

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Hypogammaglobulinemia is a medical condition in which the blood levels of immunoglobulins or antibodies are low. An immune system with this condition cannot produce enough antibodies to respond effectively to potentially harmful infections.

This condition affects both children and adults. However, it is more common in young adults. Multisystemic infections are one of the clinical symptoms of hypogammaglobulinemia.

What are the symptoms of hypogammaglobulinemia?

People with hypogammaglobulinemia are at risk of widespread infections and immune disorders.

As a result of this immunodeficiency, people are prone to infections and may develop the following conditions:

The following autoimmune conditions may also occur:

Learn more about autoimmune diseases.

What causes hypogammaglobulinemia?

Hypogammaglobulinemia occurs with either inadequate production or excess loss of antibodies. The causes are typically either primary or secondary.

Primary causes are genetic conditions that affect the production of antibodies. In contrast, secondary causes are external factors that affect the levels of antibodies.

Primary hypogammaglobulinemia

B-lymphocytes are special immune cells responsible for producing antibodies, such as: 

  • IgM
  • IgD 
  • IgG
  • IgA
  • IgE

Chromosomal and genetic mutations that affect B-lymphocytes may affect the production of antibodies. 

Transient hypogammaglobulinemia of infancy (THI) is a primary hypogammaglobulinemia. It occurs at birth and during the first few months of life. However, the antibody levels tend to gradually return to normal when the infant begins producing its own antibodies. This typically occurs during the first or second year of life.

Other examples of primary hypogammaglobulinemia include

  • X-linked agammaglobulinemia (XLA) or Bruton’s agammaglobulinemia: Inherited changes in the BTK gene cause low levels of plasma cells and immunoglobulins. This leads to decreased antibody production and response to unknown organisms.
  • Common variable immunodeficiency (CVID): In CVID, the B-cells do not work as expected. This results in low levels of plasma cells and eventually leads to low immunoglobulins.
  • Selective IgA deficiency: This occurs due to issues in IgA-secreting B-cells.
  • Hyper-IgM syndrome: A main criterion for this syndrome is that IgM levels are high, while IgG, IgA, and IgE blood concentrations are low.

Secondary hypogammaglobulinemia

People with medical conditions or those taking certain medications are at risk of secondary hypogammaglobulinemia.

Some causes of secondary hypogammaglobulinemia include:

  • Medications: These medications include steroids, immunosuppressants, and some antiseizure medications. 
  • Medical conditions: This includes renal or gastrointestinal diseases that lead to protein loss.

How is hypogammaglobulinemia diagnosed?

Diagnosis of hypogammaglobulinemia begins with a clinical history and physical examination.

Your doctor will typically ask questions to identify a history of organ infections and autoimmune conditions. Your doctor will also examine your symptoms for changes that may include:

  • enlarged liver
  • enlarged spleen
  • enlarged lymph nodes
  • eardrum perforation and scarring
  • nasal exudates and cobblestone pattern of the pharyngeal mucosa

After clinical examination, the following investigations help in confirming the hypogammaglobulinemia diagnosis:

  • serum immunoglobulin levels of IgM, IgG, IgA
  • genetic testing to identify changes in the BTK and other genes
  • complete blood count
  • other blood tests to determine the degree of infection
  • lymph node biopsy to diagnose suspected lymphomas 

What are the treatment options for hypogammaglobulinemia?

Hypogammaglobulinemia treatment aims to replace low levels of antibodies and manage your symptoms.

Immunoglobulin replacement therapy 

Immunoglobulin replacement therapy involves administering antibodies through an IV or under the skin. These antibodies come from the blood of healthy donors.

However, immunoglobulin replacement therapy is not a typical treatment for THI because THI is a temporary condition.

Therapeutic immunoglobulins have varying concentrations of antibodies. However, IgG is the predominant form of immunoglobulin in these blood products. Immunoglobulin replacement therapy involves thorough screening of recipients to reduce the risk of allergic reactions.

Some possible side effects of therapeutic immunoglobulin include: 

Doctors regularly monitor your antibody level if you are receiving immunoglobulin therapy. This helps with dosage adjustment and reduces the risk of adverse reactions.

Medications

Your doctor may prescribe antibiotics if you experience active infections. They may also recommend systemic corticosteroids if you have an autoimmune disorder.

Preventive measures

People who are immunocompromised will benefit from washing their hands regularly. Additionally, wearing face masks where appropriate can help reduce exposure to airborne microbes that cause respiratory infections.

What are the complications of hypogammaglobulinemia?

Chronic respiratory infections may lead to pulmonary complications, such as bronchiectasis. This is an abnormal lung dilation with mucus collections. Bronchiectasis may lead to respiratory distress and delay the clearance of infectious organisms.

Also, hematological cancers such as lymphomas are possible complications in long-term cases of hypogammaglobulinemia.  

Learn more about types of lymphoma.

What is the life expectancy for those with hypogammaglobulinemia?

The frequency of infection and severity of other complications determine the overall prognosis. Early diagnosis and prompt intervention may also help prevent the onset of life threatening complications.

Generally, the outlook is better for people who receive early treatment.

Summary

People with hypogammaglobulinemia have a low blood level of antibodies. They can not mount an adequate immune response to protect from infection. Hypogammaglobulinemia affects both children and adults.

Increased risk of recurring infections and autoimmune disorders are signs of hypogammaglobulinemia.

Immunoglobulin replacement therapy is the main treatment for the condition. It helps boost the blood level of antibodies. However, this treatment may not suit people who are at higher risk of allergic reactions.

Your doctor may prescribe antibiotics to prevent infection. They may also recommend corticosteroids for inflammatory and autoimmune disorders. The specific treatments your doctor suggests will depend on your overall condition.

Early diagnosis and treatment help reduce the risk of life threatening respiratory complications and lymphomas.

Speak with your doctor if you may be at risk of hypogammaglobulinemia.

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Medical Reviewer: Meredith Goodwin, MD, FAAFP
Last Review Date: 2022 Sep 2
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THIS TOOL DOES NOT PROVIDE MEDICAL ADVICE. It is intended for informational purposes only. It is not a substitute for professional medical advice, diagnosis or treatment. Never ignore professional medical advice in seeking treatment because of something you have read on the site. If you think you may have a medical emergency, immediately call your doctor or dial 911.
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  2. Huq, M., et al. (2022). Hypogammaglobulinemia. https://www.ncbi.nlm.nih.gov/books/NBK563134/
  3. Pimenta, F. M. C. A., et al. (2019). Hypogammaglobulinemia: A diagnosis that must not be ignored. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787951/