Infections in activated PI3K delta syndrome (APDS)

•APDS is caused by activating mutations in PIK3CD or PIK3R1 encoding PI3Kδ subunits.•Recurrent infection, lymphoproliferation, and immunopathology occur in APDS.•Sinopulmonary bacterial infections in APDS are linked to antibody defects.•Herpesvirus infections in APDS are associated with defective cytotoxic lymphocytes.•APDS treatments include antimicrobials, Ig supplementation, and mTOR/PI3Kδ inhibitors. Activated PI3K-delta Syndrome (APDS), also called PI3K-delta activating mutation causing senescent T cells, lymphadenopathy, and immunodeficiency (PASLI), is an autosomal dominant disorder caused by inherited or de novo gain-of-function mutations in one of two genes encoding subunits of the phosphoinositide-3-kinase delta (PI3Kδ) complex. This largely leukocyte-restricted protein complex regulates cell growth, activation, proliferation, and survival. Patients who harbor these mutations have early onset immunodeficiency with recurrent infections, lymphadenopathy, and autoimmunity. The most common infection susceptibilities are sinopulmonary (encapsulated bacteria) and herpesviruses. Multiple defects in both innate and adaptive immune function are responsible for this phenotype. Apart from anti-microbial prophylaxis and immunoglobulin replacement, patients are treated with a variety of immunomodulatory agents and some have needed hematopoietic stem cell transplants. Here, we highlight the spectrum of infections, immune defects, and therapy options in this inborn error of immunity.