10 Types of Primary Immunodeficiency: What To Know

Primary immunodeficiency (PI) — also called inborn errors of immunity — is a group of disorders that affect how the immune system works. Your immune system is your body’s defense against viruses, bacteria, and other harmful germs. When it doesn’t work properly, you may develop serious or ongoing infections.

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There are more than 500 known PI disorders. To help doctors and researchers diagnose and treat them, the International Union of Immunological Societies groups them into 10 categories based on which part of the immune system is affected. Below is a brief overview of each category, including common causes, symptoms, and treatments.

1. T-Cell and B-Cell Deficiencies

This category includes some of the most serious forms of PI, which are often diagnosed in early childhood. They affect two types of immune cells — T cells and B cells. T cells help fight off viruses and other germs, and B cells make antibodies (immune system proteins). When neither type works well, the immune system can’t protect the body as it should.

This group includes a well-known condition called severe combined immunodeficiency (SCID). Babies with SCID may seem healthy at birth but soon develop repeated infections. Some children also react poorly to live vaccines. Treatment may include:

• Stem cell transplant
• Gene therapy
• Intravenous immunoglobulin (IVIG), a type of immunotherapy
• Medications to prevent bacterial, viral, and fungal infections

Newborn screening can catch SCID early and improve survival and quality of life.

2. Antibody Deficiencies

Antibody deficiencies are the most common type of primary immunodeficiency. In antibody deficiency conditions, the body doesn’t make enough healthy antibodies — proteins that help fight infections. Without antibodies, it’s harder to control bacterial infections, especially in the ears, sinuses, and lungs.

Common conditions in this category include:

• Common variable immunodeficiency (CVID) — A disorder that causes low levels of several types of antibodies
• X-linked agammaglobulinemia — A genetic condition (passed through the X chromosome) in which the body makes almost no antibodies
• Selective IgA deficiency — The most common antibody deficiency, in which the body lacks immunoglobulin A (IgA), an antibody that protects the respiratory and digestive tracts

PI symptoms and signs depend on the exact condition but can include:

• Repeated infections
• Stomach issues
• Swollen lymph nodes
• Low platelets (blood-clotting cells) or anemia (low red blood cell counts)

Treatment often involves antibiotics for recurrent (repeated) infections. These conditions can also lead to low levels of immunoglobulins (antibodies) such as IgG, IgA, and IgM in the blood. Immunoglobulin replacement therapy, such as IVIG, can help restore these levels.

3. Combined Immune Deficiencies With Other Syndromes or Features

This category includes immune problems that are part of a larger syndrome — a condition that affects more than one part of the body. People with these conditions have trouble with both T cells and B cells. They may also have other issues such as low platelets, eczema (a skin condition that causes rashes and itch), or problems with the heart or bones.

Examples include:

• Wiskott-Aldrich syndrome — A rare condition that causes low platelets, frequent infections, and eczema
• DiGeorge syndrome (also known as 22q11.2 deletion syndrome) — A genetic condition that can cause heart defects, learning difficulties, and immune problems
• Charge syndrome — A disorder that can affect many parts of the body, including the eyes, ears, heart, and immune system

Antibiotics, immunoglobulin therapy, and, in some cases, a stem cell transplant, may be used to manage these types of disorders. Some newer treatments may target the specific gene mutations (changes) involved.

Because these syndromes can affect multiple organs, care usually involves a team of specialists, such as:

• Immunologists (immune system specialists)
• Cardiologists (heart specialists)
• Geneticists (genetic specialists)

4. Immune Dysregulation

In immune dysregulation disorders, the immune system doesn’t just fail to protect the body — it also attacks healthy tissues by mistake. This can trigger autoimmune diseases such as autoimmune hemolytic anemia, in which the body destroys its own red blood cells.

Symptoms of inflammation may include:

• Unexplained fevers
• Skin rashes
• Inflammatory bowel disease
• Joint pain
• Too many immune cells
• Swollen lymph nodes
• Severe allergies

PI examples in this category include:

• IPEX syndrome — A rare genetic disorder that causes severe autoimmune problems, such as diarrhea, rashes, and pancreas problems that can lead to type 1 diabetes
• Autoimmune lymphoproliferative syndrome — A condition in which the body can’t get rid of extra immune cells, causing swollen lymph nodes, an enlarged spleen and liver, and autoimmune symptoms

These disorders make up about 5 percent of all PI disorders and are typically diagnosed in early childhood. Treatment may involve immune-suppressing medicines and immunoglobulin therapy. Researchers are also studying gene editing as a treatment.

5. Phagocyte Cell Deficiencies

Phagocytes are a type of white blood cell that “eat” and destroy germs like bacteria and fungi. When phagocytes can’t do their job, the body has trouble fighting infections, even with normal levels of other immune cells.

People with phagocytic cell deficiencies, such as chronic granulomatous disease (CGD), often get recurrent infections like pneumonia, skin infections, or abscesses (painful, pus-filled cysts). Some people also have gastrointestinal (gut) inflammation or fungal infections. These infections can be tricky to treat, even with antibiotics. Doctors manage these conditions using:

• Prophylactic (preventive) antibiotics
• Antifungal medications
• Interferon-gamma (a protein that helps activate immune cells)
• Bone marrow or stem cell transplants
• Gene therapy

6. Intrinsic and Innate Immunity Defects

The innate immune system is the body’s first line of defense, acting quickly to stop germs before they spread. People with defects in intrinsic or innate immunity are born with genetic changes that affect the function of first-line immune cells such as:

• Barrier cells in the skin
• Neutrophils (a type of white blood cell)
• Other specialized white blood cells

These conditions often lead to recurrent bacterial, fungal, or viral infections in the skin, lungs, and brain. One example is chronic mucocutaneous candidiasis, a fungal infection caused by Candida. Another is Mendelian susceptibility to mycobacterial disease, which makes a person more vulnerable to tuberculosis and other infections. Treatment may include antibiotics, antifungals, or interferon therapy.

7. Autoinflammatory Disorders

Autoinflammatory disorders happen when the body’s inflammation signals get stuck in the “on” position. This can lead to episodes of fever, rash, joint pain, and swelling, even without infection. These problems are linked to genetic mutations in the innate (nonspecific) immune system. Unlike autoimmune disorders, these conditions don’t involve antibodies.

This category contains more than 50 known disorders, including:

• Familial Mediterranean fever — Causes repeated fevers, stomach pain, and joint swelling
• Muckle-Wells syndrome — Leads to episodes of fever, rash, joint pain, and hearing loss
• Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) — Involves repeated episodes of fever and inflammation
• Schnitzler syndrome — Causes long-lasting hives, fever, bone pain, and swollen lymph nodes

Treatment focuses on calming inflammation, relieving pain, and reducing swelling. Doctors may use anti-inflammatory drugs, steroids, or newer drugs called biologics that block overactive immune signals. Some people may need long-term care to control flare-ups.

8. Complement Deficiencies

The complement system is a group of proteins in the blood that help the immune system destroy bacteria, clear out dead cells, and control inflammation. When these proteins are missing or don’t work correctly, it’s called a complement deficiency.

People with complement deficiencies often get repeated bacterial infections, especially in the lungs, blood, and brain. They’re also prone to serious infections like meningitis or blood poisoning, which can be life-threatening without proper treatment. Some people may also have a higher risk of autoimmune diseases like lupus, especially with early C1-C4 deficiencies.

Management often includes vaccines — especially for meningitis — and antibiotics to help prevent or treat infections.

9. Bone Marrow Failure Syndromes

Bone marrow is the soft tissue inside bones where the body makes blood cells, including immune cells that fight infection. In bone marrow failure syndromes, the marrow doesn’t make enough healthy cells. This can cause problems like low white blood cells, anemia, and low platelets, leading to infections, tiredness, and bleeding.

Conditions in this group include:

• Fanconi anemia — Causes bone marrow failure
• Dyskeratosis congenita — Can trigger skin and nail changes, bone marrow failure, and lung or liver problems
• Schwachman-Diamond syndrome — Affects the bone marrow, pancreas, and bones
• GATA2 deficiency — Impacts immune cell production, causing frequent infections, low blood counts, and a higher risk of leukemia

Some of these conditions are inherited (passed down through families) and may also affect growth, skin, bones, or the pancreas. People may get frequent infections, bruise easily, or have a higher risk of leukemia or myelodysplastic syndrome.

Treatment options for this type of PI deficiency may include antibiotics, antifungal drugs, and antiviral medications. A stem cell transplant is the only proven long-term treatment.

10. Phenocopies of Primary Immunodeficiencies

Phenocopies are health problems that act like PI conditions but aren’t inherited. These conditions happen when something acquired later in life disrupts the immune system.

Common triggers include:

• A genetic mutation that develops after birth
• Autoantibodies (immune proteins that mistakenly attack the body’s own tissues)
• Environmental factors such as medications, toxins, or infections

Examples include autoantibodies against interferon gamma, which can cause severe infections, and somatic mutations — genetic changes that occur in only some of the body’s cells.

People with phenocopies often have no family history of immune problems and may have been healthy for years before primary immunodeficiency symptoms appear. These disorders are rare, making up less than 1 percent of all PI disorders. Symptoms can include severe infections, autoimmune problems, or unusual reactions to vaccines.

Diagnosis often requires advanced laboratory tests and genetic analysis. Treatment depends on the underlying cause.

Talk With Your Doctor

If you or your child has frequent infections or other immune problems, talk with your doctor. Most PI conditions are rare — but early testing and treatment can make a big difference.

Talk With Others Who Understand

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

Have you or someone in your family been diagnosed with a type of primary immunodeficiency? What symptoms have you experienced, or what treatments have you tried? Join the conversation and share your thoughts in the comments below.