Is Hypogammaglobulinemia a Primary Immunodeficiency? Explained

When your body senses a new virus, bacteria, or fungus, your immune system quickly responds. One key part of this defense involves making proteins called immunoglobulins, or antibodies, which help target and destroy the invading germs. For some people, this process doesn’t work properly, leading to low levels of antibodies in the blood. This condition is called hypogammaglobulinemia (HG).

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HG can be caused by a genetic mutation (change) passed down from a parent. In that case, it’s considered a type of primary immunodeficiency (PI) — a group of conditions you’re born with that affect the immune system. However, HG can also develop as a side effect of other conditions.

In this article, we’ll describe what happens when someone has HG, what causes this condition, how it’s diagnosed, and how it’s treated.

Causes of Hypogammaglobulinemia

HG can be caused by a gene mutation or develop later in life. When it’s genetic, the condition is present at birth and called primary HG. People with primary HG often begin having symptoms in their teens and 20s, but it can be diagnosed at any age.

Some specific conditions are types of primary HG, depending on the mutation involved. A few examples include:

• X-linked agammaglobulinemia (XLA) — Also called Bruton agammaglobulinemia, this inherited condition prevents the body from making B cells, which are needed to produce antibodies. XLA is usually diagnosed in children.
• Common variable immunodeficiency (CVID) — The most common type of primary HG in adults, CVID is caused by different gene mutations that affect the B cells’ ability to make antibodies.
• Selective IgA deficiency — In this condition, the immune system has problems making an antibody called immunoglobulin A (IgA). Some people have very low levels of IgA, and others have none at all.

Secondary HG results from another underlying condition or its treatment. Possible causes include:

• Certain types of cancer, including lymphoma and leukemia
• Some autoimmune diseases, such as lupus and rheumatoid arthritis
• Neurologic conditions (affecting the brain, spinal cord, and nerves) like multiple sclerosis
• Lung conditions such as cystic fibrosis and chronic obstructive pulmonary disease (COPD)
• Kidney problems like nephrotic syndrome
• Infections such as human immunodeficiency virus (HIV)
• Medications that weaken the immune system, such as corticosteroids or immunosuppressants

Researchers don’t fully understand why those diseases lead to HG, but nearly all are treated with immunosuppressive drugs. In many cases, the cause may be the disease itself, the treatment, or both.

It’s important to find out if someone has primary or secondary HG, because the treatments are different.

Symptoms of Hypogammaglobulinemia

The most common symptom of HG is long-lasting or frequent infections that often affect the ears, sinuses, chest, lungs, digestive system, and skin. These infections might not respond well to standard antibiotic treatment.

People with primary HG may have additional symptoms depending on their specific condition. For example, XLA often causes lung infections or sinusitis (sinus infections) from certain bacteria, including:

• Streptococcus
• Haemophilus
• Pseudomonas (called encapsulated bacteria)

In CVID, repeated sinus and lung infections are common. These infections can lead to lung damage called bronchiectasis (widened and scarred airways).

Diagnosis of Hypogammaglobulinemia

It can be hard for your healthcare team to tell if your HG is primary or secondary, especially if you also have another condition that can cause it. It’s important to work with your healthcare provider to identify the cause because effective treatment depends on knowing the source.

Immunoglobulin Blood Tests

The first step in diagnosing HG is a blood test that measures your levels of immunoglobulins — IgG, IgM, and IgA. IgG levels are usually the most important for diagnosing HG. If you have selective IgA deficiency, your IgA level will be unusually low, while the others might be normal.

Your results will be compared to the average levels for your age. Based on how low your levels are, your healthcare provider will classify your HG as mild, moderate, or severe. Low antibody levels are sometimes temporary, so the test is usually repeated over time to confirm the diagnosis.

Vaccine Responses

Vaccines help the immune system make antibodies. In people with HG, this immune response might be impaired. To test this, your provider may give you a vaccine and then check your blood four to six weeks later to see if your body made the right antibodies.

Other Tests

To find out what’s causing your low antibody levels, your doctor may order tests such as:

• Blood tests and imaging scans to check immune cell levels and organ function
• Genetic tests to screen for primary immunodeficiency mutations
• Biopsies (taking tissue samples to examine under a microscope) if cancer is suspected

Your provider will also ask about any medications you take, review your medical history (especially recurrent infections), and ask if you have a family history of immune deficiency.

Treatment Options for Hypogammaglobulinemia

Treatment options depend on whether HG is primary or secondary and how severe it is.

Options for Secondary Hypogammaglobulinemia

If a medication is lowering your antibody levels, your healthcare provider may recommend stopping or changing it. If HG is caused by another condition, treating that disease often improves antibody levels, too. If those steps aren’t options, the management plan may include:

• Closely watching for signs of infections
• Using antimicrobials (such as antibiotics) when needed
• Starting immunoglobulin replacement therapy (see below)

Options for Primary Hypogammaglobulinemia

The management plan for primary HG depends on how low your antibody levels are and whether you’ve had severe infections. Your healthcare provider may recommend:

• Monitoring if your antibody levels are stable and you’re not getting sick
• Using antimicrobials when needed to treat an infection or sometimes as a preventive step
• Starting immunoglobulin replacement therapy if your IgG levels are low enough to need regular treatment

Immunoglobulin Replacement Therapy

Immunoglobulin replacement therapy gives you antibodies from healthy donors to help protect against infections. The antibodies come from plasma — the liquid part of blood — that’s collected and combined from many donors.

The donated antibodies stay in your bloodstream for one to four weeks. If your HG doesn’t go away, you’ll need repeated treatments to stay protected. Immunoglobulin replacement therapy is a standard treatment for people with primary HG conditions such as CVID and XLA.

Check With Your Doctor

If you think you or someone you love might have HG — or if you have questions about treatment — talk with your healthcare provider. They can help you understand your options and make a plan that fits your needs.

Talk With Others Who Understand

On myPIteam, people come together to learn more about life with primary immunodeficiency disorders.

Have you or a loved one been diagnosed with hypogammaglobulinemia? What was the diagnosis and treatment process like? Share your tips and experiences in a comment below.