PI3 Kinase Disease

PI3 kinase (PI3K) disease is a rare disorder that severely impairs the immune system’s ability to fight bacterial and viral infections. The disease also increases a person’s risk of lymphoma, a type of immune cell cancer. PI3K disease is sometimes called PASLI disease (short for PI3K-p110δ activating mutation causing senescent T cells, lymphadenopathy, and immunodeficiency) or APDS (for activating PI3K delta syndrome).

NIAID scientists and their collaborators identified PI3K disease in 2013. NIAID supports research to learn more about the genetic cause of the disease and to investigate potential therapies for its symptoms and complications.

PI3K disease is caused by mutations in the genes PIK3CD or PIK3R1, which provide instructions for producing a protein called PI3K-p110δ. These mutations can affect the immune system by overactivating an important immune system signaling pathway. This overactivation launches a chain reaction leading to disruptions in the normal development of B and T cells, which play a key role in fighting pathogens, and to increased susceptibility to infection.

PI3K disease is characterized by recurrent respiratory infections that can lead to progressive airway damage. People with PI3K disease have too few of some types of immune cells and too many of others. This sometimes includes a buildup of immune cells called lymphocytes, which can lead to swelling of the lymph nodes and spleen, chronic Epstein-Barr virus and cytomegalovirus infections, and an increased risk for lymphoma. Many people with PI3K disease also have abnormal levels of certain types of antibodies.

Physicians diagnose PI3K disease based on symptoms, genetic testing, and laboratory findings.

Researchers have had some success treating PI3K disease with medications that inhibit the immune system pathway that is overactivated. In early studies, this strategy reduced swelling of the lymph nodes, most likely by restoring the normal balance of immune cells. More research is needed to determine the most effective timing and dosage of these medications and to investigate other treatment options, such as PI3K-specific drugs. Read more about NIAID research towards treatments for PI3K disease.

NIAID continues to investigate treatments for PI3K disease. Watch this video about people with PI3K disease, or PASLI disease, receiving care from NIAID physicians.

For detailed information about the cause of PI3K disease and its inheritance pattern, signs, symptoms and treatment, as well as coping strategies for affected families, please read these fact sheets on PI3K disease associated with PIK3CD mutation and PI3K disease associated with PIK3R1 mutation

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