PI3Kδ and primary immunodeficiencies

Carrie L Lucas, Anita Chandra, Sergey Nejentsev, Alison M Condliffe, Klaus Okkenhaug

Research output: Contribution to journalReview articleAcademicpeer-review

212 Citations (Scopus)


Primary immunodeficiencies are inherited disorders of the immune system, often caused by the mutation of genes required for lymphocyte development and activation. Recently, several studies have identified gain-of-function mutations in the phosphoinositide 3-kinase (PI3K) genes PIK3CD (which encodes p110δ) and PIK3R1 (which encodes p85α) that cause a combined immunodeficiency syndrome, referred to as activated PI3Kδ syndrome (APDS; also known as p110δ-activating mutation causing senescent T cells, lymphadenopathy and immunodeficiency (PASLI)). Paradoxically, both loss-of-function and gain-of-function mutations that affect these genes lead to immunosuppression, albeit via different mechanisms. Here, we review the roles of PI3Kδ in adaptive immunity, describe the clinical manifestations and mechanisms of disease in APDS and highlight new insights into PI3Kδ gleaned from these patients, as well as implications of these findings for clinical therapy.

Original languageEnglish
Pages (from-to)702-714
Number of pages13
JournalNature Reviews Immunology
Issue number11
Publication statusPublished - Nov 2016
Externally publishedYes


  • Animals
  • Cell Differentiation/genetics
  • Cellular Senescence/genetics
  • Enzyme Activation
  • Gene Expression Regulation
  • Humans
  • Immune System/cytology
  • Immunity
  • Immunologic Deficiency Syndromes/etiology
  • Lymphocyte Activation/genetics
  • Lymphocytes/cytology
  • Molecular Targeted Therapy
  • Mutation
  • Phosphatidylinositol 3-Kinases/antagonists & inhibitors
  • Protein Subunits/genetics
  • Signal Transduction

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