Primary vs. Secondary Immunodeficiency: 5 Differences and 5 Similarities

Some people are born with an immune system that doesn’t protect their body the way it should. Others develop problems with their immune system later in life. Either way, the result is a higher risk of getting sick, more frequent infections, and a need for specialized care.

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When the immune system doesn’t work properly, it’s known as an immunodeficiency. There are two types of immunodeficiency — primary immunodeficiency (PI) and secondary immunodeficiency. Both types involve problems with the immune system, but their causes and treatments are very different.

Understanding the differences and similarities between primary and secondary immunodeficiency can help you and your healthcare team find the best care plan.

5 Differences Between Primary and Secondary Immunodeficiency

Although both types affect how the immune system works, primary and secondary immunodeficiency disorders differ in important ways. Here are five key differences.

1. Primary Immunodeficiency Is a Genetic Condition

PI is caused by a genetic mutation (a change in the instructions that help the body work) that affects how the immune system develops or functions. In most cases, the mutations are inherited (passed down) from parent to child, which is why many people with PI have a family history of the condition. The genetic changes are present at birth, even if symptoms don’t appear right away.

When immunodeficiency is genetic, it’s called “primary” because the problem is present from birth — it’s part of how the body was built. This is what sets PI disorders apart from secondary immunodeficiency disorders, which are acquired from another treatment or illness, or a “secondary” cause.

2. Secondary Immunodeficiency Results From Another Condition or Treatment

Secondary immunodeficiency happens when a factor outside the immune system, such as a medical condition or treatment, weakens the immune response.

Medical Conditions Linked to Secondary Immunodeficiency

Several medical conditions can lead to secondary immunodeficiency. Worldwide, the most common cause is malnutrition. Without proper nutrition, vitamins, and minerals, the immune system can’t work the way it should.

Other causes of secondary immunodeficiency can include:

• Infections such as human immunodeficiency virus (HIV), measles, COVID-19, and tuberculosis
• Alcohol use disorder
• Kidney disease
• Liver disease
• Premature birth
• Older age
• Blood cancer
• Diabetes
• Autoimmune disorders
• Severe burns

Medical Treatments Linked to Secondary Immunodeficiency

The most common medication-related cause is a drop in antibody production, often from immunosuppressive drugs. These medications may be used to treat autoimmune diseases or blood cancers.

Other medical treatments that can cause secondary immunodeficiency include:

• Corticosteroids
• Chemotherapy
• Radiation therapy
• Biologic medications
• Anti-seizure medications

3. Secondary Immunodeficiency Is More Common Than Primary

In adults, secondary immunodeficiency is more common than PI. Because there are so many causes, it’s hard to know just how many people are affected, but secondary immunodeficiency is very common in certain conditions. For example, infections are the leading cause of death in people with chronic lymphocytic leukemia.

By comparison, PI is rare. This group of genetic conditions affects about 1 in 1,000 to 1 in 5,000 people.

4. Primary Immunodeficiency Is Often Diagnosed in Childhood

Both primary and secondary immunodeficiency can occur at any age. However, most severe cases of PI, such as severe combined immunodeficiency (SCID), are diagnosed in infancy or early childhood. Milder forms may not be recognized until adulthood. For example, common variable immunodeficiency (CVID) and specific antibody deficiency are often first diagnosed in adults.

Secondary immunodeficiency develops after other illnesses or treatments that are more common in adults.

5. Treatment for Secondary Immunodeficiency Focuses on the Cause

For secondary immunodeficiency, treatment usually starts with finding and managing the underlying cause. If the problem is linked to another medical condition, treating that issue may help the immune system to return to normal.

For example, antiviral medications can control an HIV infection and prevent further immune damage. If medications are the cause, stopping or adjusting them may improve immune response.

Additional treatments, like antibiotics or immunoglobulin replacement therapy, are sometimes needed to help prevent or manage bacterial infections in people with primary and secondary immunodeficiency. In most types of PI, treatment focuses on preventing and treating recurrent infection (repeated illness). However, new therapies are being developed to correct the underlying immune system problem.

5 Similarities Between Primary and Secondary Immunodeficiency

Primary and secondary immunodeficiency share several key features. These similarities help explain why it can be hard to tell the two apart without testing.

1. Both Types Make It Harder To Fight Infection

The main signs and symptoms of both primary and secondary immunodeficiency are the same — frequent, recurring, and hard-to-treat infections.

Different causes affect different parts of the immune system. For example, diabetes mainly affects neutrophils (a type of white blood cell), whereas HIV infection targets T cells.

Like PI, secondary immunodeficiency can lead to immune dysregulation, which may cause autoimmune disease and raise the risk of malignancy (cancer).

2. Symptoms Can Be Mild or Severe in Both

The terms “primary” and “secondary” describe the cause of immunodeficiency, not how serious it is. In both types, symptoms can range from mild to severe. For example, some people with selective IgA deficiency may not have any symptoms, whereas those with SCID have serious, life-threatening problems early in life.

Severity also varies in secondary immunodeficiency. People taking immunosuppressant medications after an organ transplant are considered severely immunocompromised. In contrast, age-related changes in the immune system may cause only a mild increase in infection risk.

3. An Immunologist Can Help Diagnose Either Type of Immunodeficiency

It can be difficult to tell primary and secondary immunodeficiency apart, but finding the cause is key to choosing the right treatment.

An immunologist (a doctor who specializes in immune system disorders) can order tests to help determine whether the cause is primary or secondary. Tests may include:

• Complete blood count
• Flow cytometry to measure different types of blood cells
• Antibody level testing

Genetic testing can help identify the specific gene change causing the condition. If secondary immunodeficiency is suspected, healthcare providers from other specialties might run more tests to uncover the underlying cause.

4. Treating the Root Cause May Boost Immune Function in Both Types

Whether immunodeficiency is inherited or acquired, targeting the source of the problem can improve immune function. Treatment for secondary immunodeficiency focuses on fixing the underlying cause or stopping the treatment that weakens the immune system. For primary immunodeficiency, treatment has usually focused on preventing and managing infections.

However, researchers have developed treatments that can restore immune function in some types of PI. For example, bone marrow transplantation (also called stem cell transplantation) replaces defective blood-forming cells with healthy ones from a donor.

An emerging treatment called gene therapy is being studied in clinical trials (studies that test new therapies for safety and effectiveness). This treatment repairs the genetic defect in a person’s stem cells to create a functional immune system.

5. Ongoing Care Improves the Outlook for Both Types

Whether immunodeficiency is primary or secondary, regular medical care is key to managing symptoms and preventing complications. People with either type need routine follow-ups and preventive care to reduce the risk of infection. Your healthcare team may involve several specialists, including your immunologist. Working together, you and your healthcare team can find the best strategies and treatment options to protect your health over time.

Find Your Team

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

Are you living with primary immunodeficiency or secondary immunodeficiency? Share your experience in the comments below.