Frequently Asked Questions about Inborn Errors of Immunity

A healthy immune system protects the human body from infection. Inborn errors of immunity occur when a genetic defect weakens or blocks the immune system. This can result in a chronic illness that increases vulnerability to infection. Some forms of inborn errors of immunity are mild and easily treated while others are potentially lethal and require early and aggressive treatment.

The first indication of an IEI is often recurring or uncommon infection. These disorders can be associated with other conditions such as cytopenia (low cell count such as white cells, red cells or platelets) and bone marrow failure (an inherited or acquired disease in which the bone marrow does not make enough blood cells). In some cases, IEIs occur with other genetic organ diseases such as skeletal or heart abnormalities.

IEIs are classified and named according to the mechanism in the immune system that is affected. Some of the more commonly seen inborn errors of immunity we treat are:

• Ataxia telangiectasia
• Chronic granulomatous disease
• Common variable immune deficiency
• Complement deficiencies
• DiGeorge syndrome
• Fanconi anemia
• Hyper IgM syndrome
• IgG subclass deficiency and specific antibody deficiency
• Omenn syndrome
• Selective IgA deficiency
• Severe combined immune deficiency
• Wiskott-Aldrich syndrome
• X-linked agammaglobulinemia

Inborn errors of immunity are a group of inherited conditions (present at birth) that affect the immune system. They are considered primary immune disorders because they are not the result of (or secondary to) another illness, drug treatment or environmental factors.

IEIs are caused by a defect in the cells of the body’s immune system. They are not contagious; however, an infection contracted as a result of the weakened immune system may be contagious. A recurrent or unusual infectious disease is frequently the first sign of an IEI.

Diagnostic tools includes a medical history, physical exam, sophisticated blood tests, bone marrow aspirate and biopsy, molecular analysis and DNA sequencing. In some cases, patients may also undergo imaging tests such as MRI or CT. Newborns are automatically screened for severe combined immunodeficiency (SCID), a life-threatening disease that occurs when a child’s bone marrow does not produce functioning white blood cells. Comer Children's is a recognized SCID center for the State of Illinois.

Inborn errors of immunity can be difficult to diagnose, and can look like a lot of other medical conditions. Seeking the combined expertise of specialists in clinical immunology, hematology, transplant and infectious diseases may provide a more comprehensive perspective on these complex conditions. Our program at Comer Children’s consists of an integrated team of experts — all leaders in their fields — who work together to accurately diagnose each patient and to develop the most effective care plan for their condition.

For many children with an immune defect, symptoms are mild and the illness may never be detected or cause problems. For children with a severe immune disorders, early detection, diagnosis and treatment are critical. Some patients may benefit from immunoglobulin replacement to prevent infections. Stem cell transplant, which uses cells from a donor to help a patient create a new immune system, only is recommended for the most serious cases of inborn errors of immunity. Stem cell transplant is a cure in most instances.

Scientists are exploring gene therapy treatment to replace the defective gene that is the basis of many IEIs. Although in an early stage for many immunodeficiency diseases, this approach is likely to be effective in the next five to ten years.