B cell dependent susceptibility to airway infection in activated PI3K-delta syndrome

We have recently described an inherited immune disorder called activated PI3K-delta syndrome (APDS). The PI3K-delta protein generates chemical signals in immune cells but in people with APDS, PI3K-delta enzyme is too active which is unusual as most immunodeficiencies are due to a proteins having reduced function. As a consequence, APDS patients suffer from recurrent bacterial chest infections. B cells are immune cells that make antibodies that protect against infection, but in people with APDS, the B cells appear to contribute to disease and may be responsible for more severe infections, such as pneumonia.

We will use blood from patients with the syndrome and tissues from mice that have been engineered to have the same disease to determine how PI3K-delta causes APDS patients to be susceptible to pneumonia. We have also commenced a clinical trial to treat APDS patients with drugs that target PI3K-delta to determine if reducing PI3K-delta enzyme activity improves immune function and reduces infections.

These studies may also indicate if other people with immunodeficiency could benefit from drugs that target PI3K-delta.