Primary Immunodeficiency Diseases

Primary immunodeficiency diseases (PIDDs)—now more commonly called inborn errors of immunity (IEI)—are rare genetic disorders that cause at least one part of the immune system to malfunction. Though many people haven’t even heard of PIDDs, these conditions can have a major impact on the people who live with them and can potentially become life-threatening

“Most [PIDDs] are characterized by an increased susceptibility to infections,” Kara Wada, MD, an allergist and immunologist at The Ohio State University Wexner Medical Center, tells SELF. “This can look different in different people. Some folks will have more frequent or repeat infections, infections that don’t improve as you would expect, or unusual or more severe infections.” However, PIDDs can cause a spectrum of symptoms, in part because there are nearly 500 conditions that scientists are aware of that fall under this umbrella—and new genetic errors linked to these conditions are being discovered every year. Individually, each PIDD is fairly rare, but when you look at them as a whole, they’re estimated to affect up to five in every 1,000 people.¹ Here’s what you should know about them.

There is a “very diverse group” of PIDDs, Otto Yang, MD, an immunologist and the associate chief of infectious diseases at UCLA Health, tells SELF. “It’s kind of like saying someone has cancer—there’s a huge range.” PIDDs are still being investigated, so “what we know [about them] is probably the tip of the iceberg,” he adds.

“There are so many diseases lumped into this category because the immune system has many parts and essential functions,” Lisa Forbes Satter, MD, an associate professor of pediatrics immunology, allergy, and retrovirology at Baylor College of Medicine, tells SELF. “There are multiple cells that contribute to our overall defense of pathogens that require our immune system to perform a very coordinated response among its various ‘danger signals.’”² 

PIDDs all have one thing in common: a dysfunctional part of the immune system, according to Barrie Cohen, MD, an immunologist and assistant professor at Rutgers Robert Wood Johnson Medical School. The list of PIDDs is vast, so they are clustered into subgroups. For example, B-cell immunodeficiencies—which refer to diseases that stem from a lack of antibodies made by B cells (a type of white blood cell)—include selective IgA deficiency and common variable immunodeficiency (CVID), both of which are more commonly diagnosed.³ Meanwhile, combined immunodeficiencies—which refer to diseases that stem from the defective development or function of infection-fighting T cells—include conditions like severe combined immunodeficiency (SCID, which typically causes an infant to be born with little to no immune system) and Wiskott-Aldrich syndrome (which is characterized by having white blood cells that are abnormal or don’t function).⁴ There are other subgroups as well, and they each focus on different parts of the immune system.⁵

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Because people with a PIDD have an immune system that doesn’t work correctly, they’re more likely to get infections and become very sick from them, according to the Centers for Disease Control and Prevention (CDC). “Many PIDDs [lead to] repeated or deep infections that occur in unusual places,” Dr. Cohen says. “However, the type of infection—bacterial, viral, or fungal—will vary based on which part of the immune system is not working properly.” 

Symptoms can vary widely, but the CDC and Mayo Clinic say they may include the following:

• More frequent or repeated infections, including ear infections, sinus infections, pneumonia, bronchitis, meningitis, and skin infections, among others
• Infections that last longer than in most people
• Infections that are hard to treat and don’t respond well to antibiotics
• Infections that are more severe and require hospitalization
• Infections that most people don’t get
• Inflammation and infection of internal organs
• Digestive problems, like chronic diarrhea
• Delayed infant growth and development 
• Coexisting autoimmune diseases, like lupus, type 1 diabetes, or rheumatoid arthritis

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PIDDs are caused by genetic abnormalities that prevent the immune system from mounting a robust response, according to the National Institute of Allergy and Infectious Diseases (NIAID). As a result, having a family history of inborn errors of immunity raises the risk that someone will develop a PIDD, according to the American Academy of Allergy Asthma & Immunology (AAAAI). “Even though many PIDDs are genetic, they may not cause symptoms until adulthood,” Dr. Cohen says. 

Genetic mutations can happen randomly, however, and don’t necessarily need to be passed down from your relatives, the NIAID says. For example, a secondary immune deficiency disease can develop when the immune system becomes compromised in response to an environmental factor including a severe and prolonged infection (like HIV), immunosuppressive medical treatment (like chemotherapy), severe burns, or even malnutrition, the AAAAI says.⁶ If someone is already susceptible to a PIDD, and then is exposed to certain triggers, it can “turn on or turn off genes,” Dr. Wada explains. “This may then result in a PIDD presenting and then being diagnosed later in life.”

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The best treatment and care really depend on the disease and an individual’s needs, Dr. Yang says. According to the CDC, that can include:

• Long-term or intravenous antibiotics to treat and prevent recurrent infections
• Treatments that help your immune system function better, like immunoglobulin therapy and interferon-gamma therapy 
• Growth factors to help increase the number of white blood cells in the body
• Bone marrow or stem cell transplant to provide the body with working immune cells from another person 
• Gene therapy to correct and replace the gene that doesn’t work properly via stem cell technology

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You can’t magically “boost” a weakened immune system—but you can do certain things to support it, according to the CDC and the Mayo Clinic:

• Wash your hands well and often.
• Take good care of your teeth by brushing them twice daily.
• Find a form of movement you enjoy and practice it regularly.
• Enjoy a diet that’s balanced in nutrients and rich in colorful foods.
• Aim for at least seven hours of sleep a night.
• Do your best to avoid people who are sick, as well as crowds.
• Wear a well-fitting face mask in public and in crowded areas. 
• Stay up to date on your recommended vaccinations, but talk to your doctor about which ones are right for you (some people with a PIDD can’t receive live vaccines).

If you can, try to lower the levels of stress in your life too. “Any time the body is stressed,” Dr. Satter says, “the immune system is stressed as well.”

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Sources: 

1. UpToDate, Inborn Errors of Immunity (Primary Immunodeficiencies): Classification
2. Institute for Quality and Efficiency in Health Care, How Does the Immune System Work?
3. Human Immunology, Primary B-Cell Immunodeficiencies
4. ScienceDirect, Combined Immunodeficiencies
5. Allergy, Asthma, & Clinical Immunology, Primary Immunodeficiency
6. Merck Manual, Approach to the Patient With Suspected Immunodeficiency