ArticleThe Journal of experimental medicine2023
Human PIK3R1 mutations disrupt lymphocyte differentiation to cause activated PI3Kδ syndrome 2.
Article in The Journal of experimental medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 31 citations in OpenAlex.
- Beyond B cells: T and Innate Immune Mechanisms of Autoimmunity in Common Variable Immunodeficiency.Clinical reviews in allergy & immunology · 2026Review
- Deleterious germline CARD11 gain-of-function variants alter human B-cell and CD4+ T-cell differentiation and function.Clinical and experimental immunology · 2026Article
- T follicular helper cells in primary immune regulatory disorders.The Journal of allergy and clinical immunology · 2025Review
- Powerful gene network enrichment analysis and its application to severe COVID-19 gene network.Briefings in bioinformatics · 2025Article
- Mapping the Potential Genes and Associated Pathways Involved in Long COVID-Associated Brain Fog Using Integrative Bioinformatics and Systems Biology Strategy.Molecular biotechnology · 2025Article
- PI3K GOF leads to dysregulation of T and B cells that both contribute to extrinsically driving activation and differentiation of other CD4Immunology and cell biology · 2025Article
- Article
- Human genetic influences on early B cell development.Journal of human immunity · 2025Review
- Carbon dot-based treatment for bacterial pneumonia by promoting a PI3K-mediated M1 polarization of macrophages.Journal of nanobiotechnology · 2025Article
- Correlation Between PIK3R1 Expression and Cell Growth in Human Breast Cancer Cell Line BT-474 and Clinical Outcomes.World journal of oncology · 2025Article
- Article
- Comparative efficacy of leniolisib (CDZ173) versus standard of care on rates of respiratory tract infection and serum immunoglobulin M (IgM) levels among individuals with activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS): an externally controlled study.Clinical and experimental immunology · 2025Article
- Single-nuclei transcriptome analysis of IgMFrontiers in immunology · 2025Article
- EBV-positive diffuse large B cell lymphoma secondary to activated phosphoinositide 3 kinase δ syndrome type 1 (APDS1): a case report and literature review.Frontiers in immunology · 2025Review
- Lymphoproliferation and hyper-IgM as the first manifestation of activated phosphoinositide 3-kinase δ syndrome: A case report.Biomedica : revista del Instituto Nacional de Salud · 2024Article
- Report of the Italian Cohort with Activated Phosphoinositide 3-Kinase δ Syndrome in the Target Therapy Era.Journal of clinical immunology · 2024Article
- Paradoxical dominant negative activity of an immunodeficiency-associated activatingbioRxiv : the preprint server for biology · 2024Article
- TThe Journal of allergy and clinical immunology · 2024Review
- Herb pair of Huangqi-Danggui exerts anti-tumor immunity to breast cancer by upregulating PIK3R1.Animal models and experimental medicine · 2024Article
- Hyperactivation of the PI3K pathway in inborn errors of immunity: current understanding and therapeutic perspectives.Immunotherapy advances · 2024Review
Corrections and comments
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Authors and funding
29 authors at 12 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heterozygous loss-of-function (LOF) mutations in PIK3R1 (encoding phosphatidylinositol 3-kinase [PI3K] regulatory subunits) cause activated PI3Kδ syndrome 2 (APDS2), which has a similar clinical profile to APDS1, caused by heterozygous gain-of-function (GOF) mutations in PIK3CD (encoding the PI3K p110δ catalytic subunit). While several studies have established how PIK3CD GOF leads to immune dysregulation, less is known about how PIK3R1 LOF mutations alter cellular function. By studying a novel CRISPR/Cas9 mouse model and patients' immune cells, we determined how PIK3R1 LOF alters cellular function. We observed some overlap in cellular defects in APDS1 and APDS2, including decreased intrinsic B cell class switching and defective Tfh cell function. However, we also identified unique APDS2 phenotypes including defective expansion and affinity maturation of Pik3r1 LOF B cells following immunization, and decreased survival of Pik3r1 LOF pups. Further, we observed clear differences in the way Pik3r1 LOF and Pik3cd GOF altered signaling. Together these results demonstrate crucial differences between these two genetic etiologies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.