Modulating the PI3K Signalling Pathway in Activated PI3K Delta Syndrome: a Clinical Perspective

Lucinda J Berglund

doi:10.1007/s10875-023-01626-0

Modulating the PI3K Signalling Pathway in Activated PI3K Delta Syndrome: a Clinical Perspective

J Clin Immunol. 2023 Dec 27;44(1):34. doi: 10.1007/s10875-023-01626-0.

Author

Lucinda J Berglund^{1

2}

Affiliations

¹ Faculty of Medicine, University of Sydney, Sydney, NSW, Australia. Lucinda.Berglund@sydney.edu.au.
² Department of Immunopathology, Westmead Hospital, NSW Health Pathology, Westmead, Sydney, NSW, Australia. Lucinda.Berglund@sydney.edu.au.

Abstract

Activated phosphoinositide-3-kinase (PI3K) δ syndrome (APDS) is an inborn error of immunity characterised by immune dysregulation. Since the discovery of genetic mutations resulting in PI3Kδ overactivation, treatment of APDS patients has begun to focus on modulation of the PI3K pathway in addition to supportive therapies. The mTOR inhibitor sirolimus has been used effectively for some clinical manifestations of this condition, however the arrival of specific PI3Kδ inhibitor leniolisib has shown promising early results and may provide a more targeted approach. This review summarizes key aspects of PI3K pathway biology and discusses potential options for nuanced modulation of the PI3K pathway in APDS from a clinical perspective, highlighting differences from PI3K inhibition in haematological malignancies.

Keywords: APDS; Activated PI3K delta syndrome; leniolisib; sirolimus.

Publication types

Review

MeSH terms

Class I Phosphatidylinositol 3-Kinases / genetics
Humans
Immunologic Deficiency Syndromes* / genetics
Phosphatidylinositol 3-Kinase / therapeutic use
Phosphatidylinositol 3-Kinases / genetics
Primary Immunodeficiency Diseases*

Substances

Phosphatidylinositol 3-Kinase
Phosphatidylinositol 3-Kinases
Class I Phosphatidylinositol 3-Kinases