Interferon Gamma, Interleukin 12, and Interleukin 23 Deficiencies

The immune system is a network of cells, tissues, and organs that work together to protect the body from infection. Immune cells communicate using a series of signals that can be secreted into the cell’s environment or expressed on the surface of the cell. Interferon gamma (IFN-γ), interleukin 12 (IL-12), and interleukin 23 (IL-23) are key signal molecules that raise an alert against bacteria and other infectious microbes. People with deficiencies in one or more of these signal molecules are susceptible to infections caused by certain bacteria, such as Mycobacteria, Salmonella, and Listeria, and viruses, such as herpes.

Why Is the Study of Interferon Gamma, Interleukin 12, and Interleukin 23 Deficiencies a Priority for NIAID?

Interferon gamma, interleukin 12, and interleukin 23 deficiencies are rare genetic diseases that may be chronic, debilitating, and costly. By learning more about these diseases and their effects on the body, scientists gain a greater understanding of immune function that can inform multiple areas of research.

How Is NIAID Addressing This Critical Topic?

NIAID supports basic immunology research that investigates the function of immune signal molecules, including IFN-γ, IL-12, and IL-23, to better understand how deficiencies affect patients and which therapies may be useful to improve patient outcomes.

Interferon gamma, interleukin 12, and interleukin 23 deficiencies are primary immune deficiency diseases (PIDD). For more information on PIDD research and patient care at NIAID, visit the NIAID PIDD site

People with IFN-γ, IL-12, or IL-23 deficiencies are susceptible to Mycobacteria infections, including M. tuberculosis bacteria.
Credit: NIAID
People with IFN-γ, IL-12, or IL-23 deficiencies are susceptible to Mycobacteria infections, including M. tuberculosis bacteria
Causes

Disease-causing mutations that interfere with IFN-γ, IL-12, and IL-23 signaling have been identified in the following genes: IFNGR1, IFNGR2, STAT1, IL12B, IL12RB1, NEMO. Generally, mutations in these genes will render immune cells unresponsive to IFN-γ, IL-12, or IL-23 signals in the surrounding tissue or prevent immune cells from producing IL-12 and IL-23 altogether. These mutations can be inherited in an autosomal dominant or recessive pattern.

Symptoms & Diagnosis

People with deficiencies in IFN-γ, IL-12, or IL-23 experience severe, recurring infections, especially those caused by Mycobacteria. As a result of these infections, patients with these signal molecule deficiencies may develop granulomas, inflammatory lesions that form in tissues and organs. Depending on which mutation is causing the disease, symptoms may appear early, during infancy and childhood, or later on in life. Genetic testing can determine if a person has a mutation in one of the genes involved in IFN-γ, IL-12, or IL-23 signaling.

Treatment

A physician may prescribe antibiotic therapy to prevent infections. Bone marrow transplantation, which replaces defective immune cells with those from a healthy donor, has been used in patients with these deficiencies successfully.

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Content last reviewed on June 24, 2016