Activated PI3Kinase Delta Syndrome-A Multifaceted Disease

Romane Thouenon; Nidia Moreno-Corona; Lucie Poggi; Anne Durandy; Sven Kracker

doi:10.3389/fped.2021.652405

Activated PI3Kinase Delta Syndrome-A Multifaceted Disease

Front Pediatr. 2021 Jun 25:9:652405. doi: 10.3389/fped.2021.652405. eCollection 2021.

Authors

Romane Thouenon¹, Nidia Moreno-Corona¹, Lucie Poggi¹, Anne Durandy¹, Sven Kracker¹

Affiliation

¹ Laboratory of Human Lymphohematopoiesis, Imagine Institute, INSERM UMR 1163, Université de Paris, Paris, France.

Abstract

Autosomal dominant gain-of-function mutations in the PIK3CD gene encoding the catalytic subunit p110δ of phosphoinositide 3-kinase-δ (PI3K-δ) or autosomal dominant loss-of-function mutations in the PIK3R1 gene encoding the p85α, p55α and p50α regulatory subunits cause Activated PI3-kinase-δ syndrome (APDS; referred as type 1 APDS and type 2 APDS, respectively). Consequences of these mutations are PI3K-δ hyperactivity. Clinical presentation described for both types of APDS patients is very variable, ranging from mild or asymptomatic features to profound combined immunodeficiency. Massive lymphoproliferation, bronchiectasis, increased susceptibility to bacterial and viral infections and, at a lesser extent, auto-immune manifestations and occurrence of cancer, especially B cell lymphoma, have been described for both types of APDS patients. Here, we review clinical presentation and treatment options as well as fundamental immunological and biological features associated to PI3K-δ increased signaling.

Keywords: PI3K signaling; PIK3CD; PIK3R1; lymphoproliferation; primary immunodeficiency.

Publication types

Review