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. PI3K disease also increases a person’s risk of lymphoma, a type of immune cell cancer. The disease also is called PI3K-p110δ activating mutation causing senescent T cells, lymphadenopathy, and immunodeficiency (PASLI) or activating PI3K delta syndrome (APDS). NIAID scientists and their collaborators identified the disease in 2013. NIAID supports research to learn more about the genetic cause of PI3K disease and investigates potential therapies for its symptoms and complications.

PI3K disease is caused by mutations in the genes PIK3CD or PIK3R1, which provide instructions for production of a protein called PI3K-p110δ. These mutations can affect the immune system by over-activating an important immune system signaling pathway. This activation launches a chain reaction leading to disruptions in the normal development of B and T cells and an increase in a person’s susceptibility to infection.

PI3K disease is characterized by recurrent respiratory infections, which can lead to progressive airway damage. People with PI3K disease may also experience 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 developing lymphoma.

PI3K disease is diagnosed based on symptoms, genetic testing, and laboratory findings. People with PI3K disease have too few of some immune cell types and too many of other types, which can be determined with blood tests. Many also have abnormal levels of certain types of immunoglobulins, or antibodies.

Researchers have had some success treating PI3K disease with medications that inhibit the immune system pathway that is over-activated in people with the disease. 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 this medication 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 PI3K disease, or PASLI disease, patients 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 this fact sheet on PI3K disease associated with PIK3CD mutation and this fact sheet on PI3K disease associated with PIK3R1 mutation

Content last reviewed on October 17, 2017