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

Activated PI3Kinase Delta Syndrome-A Multifaceted Disease

Romane Thouenon  1 , Nidia Moreno-Corona  1 , Lucie Poggi  1 , Anne Durandy  1 , Sven Kracker  1
Affiliations
Review

Activated PI3Kinase Delta Syndrome-A Multifaceted Disease

Romane Thouenon et al. Front Pediatr. .

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.

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Conflict of interest statement

SK reports grants and payments for service agreements and travel from UCB Pharma and is a designated inventor on published patent application WO2017/198590. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of PI3K pathway activation and downstream signaling molecules in B, T, and NK cells.
See this image and copyright information in PMC

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