How Common Is Primary Immunodeficiency?

While primary immunodeficiency (PI) is not a new set of conditions, advances in diagnosis and treatment are making them easier to manage. These conditions — also called primary immunodeficiency diseases — share an important feature: They increase the risk of frequent or severe infections, and in some cases can also be linked to allergies or autoimmune disorders (when the immune system mistakenly attacks the body).

Thanks! You've successfully submitted your vote.

Sign up to view the results!

Continue with Facebook

Sign up with your email

By joining, you accept our Terms of Use, and acknowledge our collection, sharing, and use of your data in accordance with our Health Data and Privacy policies.

Already a Member? Log in

There are more than 500 known types of PI. However, health experts estimate that 70 percent to 90 percent of people living with a PI disorder remain undiagnosed. If you’ve already received a PI diagnosis, you’ve taken an important step in getting treatment that can improve your quality of life.

In this article, we’ll discuss how common PI is, highlight several of the most common types, and explain why these conditions are often underdiagnosed.

Understanding Primary Immunodeficiency

If you have a PI disorder, it means part of your immune system is missing or not working as it should. A healthy immune system protects you from infections and helps you recover from illness or injury. When your immune system doesn’t function properly because of PI, you may be more likely to develop infections, and you may have a harder time recovering.

Infections are not the only concern with PI. People with PI are also at higher risk for:

• Allergies
• Autoimmune disorders
• Chronic inflammation (ongoing irritation and swelling in different parts of the body)

PI conditions are chronic (long term). Infections linked to PI can become persistent or difficult to treat, which may have lasting health effects.

Because primary immunodeficiency is underdiagnosed and underreported, researchers estimate that as many as 1 in 100 people have a primary immunodeficiency.

These conditions are genetic, meaning they develop from inherited changes in the immune system. This makes them different from secondary immunodeficiency, which develops later in life as a result of another health issue, such as:

• Diabetes
• Human immunodeficiency virus (HIV)
• Severe malnutrition

Certain medications that suppress or weaken the immune system (such as chemotherapy or long-term steroid use) can also lead to secondary immunodeficiency.

Risk Factors for Primary Immunodeficiency

PI conditions are caused by inherited differences in a person’s genes. They are not the result of lifestyle choices or behaviors.

Anyone, regardless of age, race, ethnicity, gender, or sex, can be affected by PI. Research shows that slightly more males than females have been diagnosed with PI, according to research in Expert Review of Clinical Immunology.

Symptoms can begin at any age. Some people show signs in infancy or early childhood, while others are not diagnosed until adulthood.

Why Primary Immunodeficiency Goes Undiagnosed

PI can cause a wide range of symptoms — including frequent infections and autoimmune problems. In some cases, though, a PI condition may cause very few symptoms at all. Because of this, recognizing the signs can be difficult.

Awareness of PI is still limited, even among some healthcare providers. This lack of familiarity is one reason why PI is often missed, delayed, or mistaken for another condition.

How Many People Have a Primary Immunodeficiency Condition?

Reported cases show that between 1 in 8,500 and 1 in 10,000 people are diagnosed with PI in some countries, while in others, it is reported as rarely as 1 in 100,000. These numbers reflect only people who have noticeable symptoms and who receive a diagnosis.

Because PI is underdiagnosed and underreported, researchers estimate that as many as 1 in 100 people have a PI.

As awareness of PI grows, diagnoses are increasing. One study found that healthcare providers reported a 96.3 percent rise in U.S. PI diagnoses and an 86.1 percent rise worldwide between 2013 and 2021.

Most Common Types of Primary Immunodeficiency

Of the more than 500 known types of PI, some are diagnosed more frequently and are easier for healthcare providers to recognize. In the United States, about 57 percent of diagnosed cases fall into a category called humoral immunodeficiencies. These conditions involve low levels of antibodies (proteins in the blood that normally help fight infections).

Below are four of the most commonly diagnosed types of PI in North America and their estimated frequencies.

Common Variable Immunodeficiency

Common variable immunodeficiency (CVID) accounts for 35 percent of diagnosed PI cases in the United States. It’s the most common PI in adults and affects an estimated 1 in 25,000 people.

With CVID, the body does not make enough antibodies to fight infections. People with CVID tend to get sick more often and more severely than others, especially with sinus infections, ear infections, and respiratory infections. Vaccines may be less effective for people with CVID because the immune system does not respond as well.

Immunoglobulin A Deficiency

Around 26 percent of people diagnosed with PI in the United States have an immunoglobulin A (IgA) deficiency. IgA antibodies normally help protect the airways, mouth, ears, eyes, and digestive system from infection.

Many people with IgA deficiency have no noticeable symptoms, but the condition can increase the risk of frequent infections. People with IgA deficiency are also more likely to have allergies, asthma, or autoimmune conditions that affect the digestive system.

Immunoglobulin G Subclass Deficiencies

Immunoglobulin G (IgG) subclass deficiencies account for around 9 percent of PI cases in the United States. People with this condition do not make enough of one or more of the four IgG antibody types.

Each IgG subclass has a different role. For example:

• IgG1 helps protect against bacterial toxins (like tetanus) and many viral infections.
• IgG2 plays a key role in defending against certain bacteria, such as streptococcus (strep).

People with an IgG subclass deficiency often experience infections tied to the missing antibody’s usual role.

Severe Combined Immunodeficiency

Severe combined immunodeficiency (SCID) is tied with IgG subclass deficiencies as the third most common type of PI in the United States, each making up about 9 percent of diagnosed cases. SCID is rare overall, affecting about 1 in 50,000 people in the U.S.

SCID affects white blood cells called lymphocytes — specifically T cells, which are crucial for fighting infections and helping B cells make antibodies. Without enough functional T cells, people with SCID are highly vulnerable to severe infections.

SCID is usually diagnosed in infancy and can be life-threatening without treatment. Babies with SCID may develop infections that are unusually severe or persistent.

Signs of SCID can include:

• Frequent and severe infections
• Diarrhea that doesn’t go away
• Trouble gaining weight and growing as expected

The Importance of Early Diagnosis

Getting diagnosed with PI early can lower the risk of complications, improve quality of life, and reduce healthcare costs. However, because PI can cause a wide variety of symptoms, it is not always simple to recognize and diagnose.

When PI is missed or mistaken for another condition, people may not get the treatment they need. Without the right treatment, infections and other complications can become more serious and may even lead to long-term health problems or disability.

Advances in DNA gene-sequencing technologies — including technologies such as next-generation sequencing (NGS) — are helping specialists identify PI more accurately. Improved screening tools and greater awareness of warning signs are also making earlier diagnosis possible.

If you have frequent or unusual infections, ask your doctor whether genetic testing or blood tests might help to diagnose PI. Early evaluation by an immunology specialist can make a big difference.

Talk With Others Who Understand

On myPIteam, people share their experiences with primary immunodeficiency disorders, get advice, and find support from others who understand.

Have you or a loved one been diagnosed with primary immunodeficiency? Share your experience in the comments below.