ArticleThe Journal of allergy and clinical immunology2017
Clinical spectrum and features of activated phosphoinositide 3-kinase δ syndrome: A large patient cohort study.
Registry-linked trialOpen access · hybridAbstract read
In one paragraph
Article in The Journal of allergy and clinical immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03383380 (Efficacy and Safety of Rapamycin Therapy for Patients With Activated Phosphoinositide 3-Kinase δ Syndrome), which is not on this map. Cited by 253 papers, 7 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
253citing papers in PubMed, 7 pooled it
21.9field-weighted citation impact, top 1% of its field
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Efficacy and Safety of Rapamycin Therapy for Patients With Activated Phosphoinositide 3-Kinase δ Syndrome
Who cites it
253 citing papers in PubMed, 7 syntheses or guidelines pooled it, 438 citations in OpenAlex.
- Systematic literature reviews to identify epidemiological, clinical, economic and health-related quality of life evidence in activated PI3Kδ syndrome (APDS).BMC immunology · 2025Pooled it
- Prevalence of Ophthalmological Manifestations in Patients with Inborn Errors of Immunity: A Systematic Review and Meta-Analysis.Journal of clinical immunology · 2025Pooled it
- Genetic Etiologies and Outcomes in Malignancy and Mortality in Activated Phosphoinositide 3-Kinase Delta Syndrome: A Systematic Review.Advances in therapy · 2025Pooled it
- Monogenic etiologies of persistent human papillomavirus infections: A comprehensive systematic review.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Pooled it
- Systematic review of mortality and survival rates for APDS.Clinical and experimental medicine · 2024Pooled it
- Clinical, Immunological, and Genetic Features in Patients with Activated PI3Kδ Syndrome (APDS): a Systematic Review.Clinical reviews in allergy & immunology · 2020Pooled it
- A Systematic Review on Predisposition to Lymphoid (B and T cell) Neoplasias in Patients With Primary Immunodeficiencies and Immune Dysregulatory Disorders (Inborn Errors of Immunity).Frontiers in immunology · 2019Pooled it
- Evaluating the impact of leniolisib treatment on symptoms and health-related quality of life in activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome.Frontiers in immunology · 2026Trial
- Associations Between Short-Term Changes in Disease Activity and Long-Term Clinical Outcomes in Activated Phosphoinositide 3-Kinase Delta Syndrome.Journal of immunology research · 2026Trial
- A randomised, placebo-controlled, phase III trial of leniolisib in activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS): Adolescent and adult subgroup analysis.Clinical immunology (Orlando, Fla.) · 2025Trial
- Trial
- Open-label extension study of leniolisib in activated PI3Kδ syndrome: Long-term efficacy and safety.Journal of human immunity · 2027Article
- How I treat: Diagnostic clues and treatment for activated phosphoinositide 3-kinase delta syndrome.Journal of human immunity · 2026Review
- When to consider an inborn error of immunity: clues for physicians.Internal medicine journal · 2026Review
- Clinical and immunological spectrum of five patients with activated phosphoinositide 3-kinase δ syndrome 1: A multicentric study from India.Journal of human immunity · 2026Article
- A review of PI3K/AKT/mTOR inhibitors from traditional Chinese medicine: potential and perspective for activated phosphoinositide 3-kinase δ syndrome.Orphanet journal of rare diseases · 2026Review
- Activated PIK3CD drives marginal zone B cell development from early transitional progenitors by enhancing ADAM10 expression.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Abnormal immunoglobulin expression and B-cell follicle organization in inborn errors of immunity/primary immunodeficiency.Virchows Archiv : an international journal of pathology · 2026Article
- IOA-244, a novel p110δ PI3K inhibitor, blocks breast tumour progression on either mono- or combined-therapy.Cell death discovery · 2026Article
- APDS in a 3-year-old boy presenting with EBV viremia and hodgkin lymphoma associated with a novel germline heterozygous variant in PIK3CD and with characteristic immune phenotype but no upregulation of the T cell mTOR pathway.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2026Article
193 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
58 authors at 20 institutions in 9 countries.
Tanya I CoulterDepartment of Immunology, School of Medicine, Trinity College, Dublin, and St James's Hospital, Dublin, Ireland; Department of Paediatric Immunology and Infectious Diseases, Our Lady's Children's Hospital Crumlin, Dublin, Ireland.
Anita ChandraDepartment of Clinical Biochemistry and Immunology, Addenbrooke's Hospital, Cambridge, United Kingdom; Lymphocyte Signalling & Development, Babraham Institute, Cambridge, United Kingdom; Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
Chris M BaconNorthern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, United Kingdom; Northern England Haemato-Oncology Diagnostic Service, Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.
Judith BabarDepartment of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
James CurtisDepartment of Medicine, University of Cambridge, Cambridge, United Kingdom.
Nick ScreatonDepartment of Radiology, Papworth Hospital NHS Foundation Trust, Papworth Everard Hospital, Cambridge, United Kingdom.
John R GoodladDepartment of Pathology, Western General Hospital, Edinburgh, United Kingdom.
George FarmerRaigmore Hospital, Inverness, United Kingdom.
Cathal Laurence SteeleRegional Immunology Service, The Royal Hospitals, Belfast, United Kingdom.
Timothy Ronan LeahyDepartment of Paediatric Immunology and Infectious Diseases, Our Lady's Children's Hospital Crumlin, Dublin, Ireland.
Rainer DoffingerDepartment of Clinical Biochemistry and Immunology, Addenbrooke's Hospital, Cambridge, United Kingdom; National Institute for Health Research, Cambridge Biomedical Research Centre, Cambridge, United Kingdom.
Helen BaxendalePapworth Hospital NHS trust, Papworth Everard, Cambridge, United Kingdom.
Jolanta BernatonieneDepartment of Infectious Disease and Immunology, University Hospitals Bristol NHS Foundation Trust, Bristol Royal Hospital for Children, Bristol, United Kingdom.
J David M EdgarRegional Immunology Service, The Royal Hospitals, Belfast, United Kingdom.
Hilary J LonghurstBarts Health NHS Trust, London, United Kingdom.
Stephan EhlCenter for Chronic Immunodeficiency, University Hospital Freiburg, Freiburg, Germany.
Carsten SpeckmannCenter for Chronic Immunodeficiency, University Hospital Freiburg, Freiburg, Germany; Department of Pediatrics and Adolescent Medicine, University Medical Center, Freiburg, Germany.
Bodo GrimbacherCenter for Chronic Immunodeficiency, University Hospital Freiburg, Freiburg, Germany.
Anna SedivaInstitute of Immunology, University Hospital Motol, Prague, Czech Republic.
Tomas MilotaInstitute of Immunology, University Hospital Motol, Prague, Czech Republic.
Saul N FaustFaculty of Medicine and Institute of Life Sciences, University of Southampton, Southampton, United Kingdom; NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
Anthony P WilliamsFaculty of Medicine and Institute of Life Sciences, University of Southampton, Southampton, United Kingdom.
Grant HaymanDepartment of Immunology, Epsom & St Helier University Hospitals NHS Trust, Surrey, United Kingdom.
Zeynep Yesim KucukDivision of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Rosie HagueDepartment of Royal Hospital for Children, Glasgow, United Kingdom.
Paul FrenchDepartment of Pathology, Queen Elizabeth University Hospital, Glasgow, United Kingdom.
Richard BrookerRoyal Aberdeen Childrens' Hospital, Aberdeen, United Kingdom.
Peter ForsythRaigmore Hospital, Inverness, United Kingdom.
Richard HerriotRoyal Aberdeen Childrens' Hospital, Aberdeen, United Kingdom.
Caterina CancriniDepartment of Pediatrics, Ospedale Pediatrico Bambino Gesù and University of Rome "Tor Vergata", Rome, Italy.
Paolo PalmaDepartment of Pediatrics, Ospedale Pediatrico Bambino Gesù and University of Rome "Tor Vergata", Rome, Italy.
Paola AriganelloDepartment of Pediatrics, Ospedale Pediatrico Bambino Gesù and University of Rome "Tor Vergata", Rome, Italy.
Niall ConlonDepartment of Immunology, School of Medicine, Trinity College, Dublin, and St James's Hospital, Dublin, Ireland.
Conleth FeigheryDepartment of Immunology, School of Medicine, Trinity College, Dublin, and St James's Hospital, Dublin, Ireland.
Patrick J GavinDepartment of Paediatric Immunology and Infectious Diseases, Our Lady's Children's Hospital Crumlin, Dublin, Ireland.
Alison JonesDepartment of Immunology, Great Ormond Street Hospital NHS Foundation Trust, London, United Kingdom.
Kohsuke ImaiDepartment of Community Pediatrics, Perinatal and Maternal Medicine Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
Mohammad A A IbrahimKing's College London, King's Health Partners, King's College Hospital NHS Foundation Trust, School of Medicine, Division of Asthma, Allergy & Lung Biology, Department of Immunological Medicine, London, United Kingdom.
Gašper MarkeljDepartment of Allergology, Rheumatology and Clinical Immunology, University Children's Hospital, University Medical Center, Ljubljana, Slovenia.
Mario AbinunDepartment of Paediatric Immunology, Newcastle upon Tyne hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom.
Frédéric Rieux-LaucatUniversité Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; INSERM UMR1163, Paris, France.
Sylvain LatourUniversité Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; INSERM UMR1163, Paris, France.
Isabelle PellierUnité d'Onco-hémato-immunologie Pédiatrique, CHU Angers, Angers, France; Centre de Référence Déficits Immunitaires Héréditaires, AP-HP, Paris, France; Inserm UMR 892, Angers, France; CNRS UMR 6299, Angers, France.
Alain FischerUniversité Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; INSERM UMR1163, Paris, France; Department of Pediatric Immunology, Hematology and Rheumatology, AP-HP, Necker Children's Hospital, Paris, France; Collège de France, Paris, France.
Fabien TouzotDépartment de Biothérapie, Centre d'Investigation Clinique intégré en Biothérapies, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; INSERM UMR1163, Paris, France.
Jean-Laurent CasanovaUniversité Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; Department of Pediatric Immunology, Hematology and Rheumatology, AP-HP, Necker Children's Hospital, Paris, France; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Imagine Institute, Necker Children's Hospital, Paris, France; St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY; Howard Hughes Medical Institute, Chevy Chase, Md.
Anne DurandyUniversité Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; INSERM UMR1163, Paris, France.
Siobhan O BurnsUniversity College London Institute of Immunity and Transplantation, London, United Kingdom.
Sinisa SavicDepartment of Clinical Immunology and Allergy, St James's University Hospital, Leeds, United Kingdom.
D S KumararatneDepartment of Clinical Biochemistry and Immunology, Addenbrooke's Hospital, Cambridge, United Kingdom.
Despina MoshousUniversité Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; Department of Pediatric Immunology, Hematology and Rheumatology, AP-HP, Necker Children's Hospital, Paris, France.
Sven KrackerUniversité Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; INSERM UMR1163, Paris, France.
Bart VanhaesebroeckUCL Cancer Institute, University College London, London, United Kingdom.
Klaus OkkenhaugLymphocyte Signalling & Development, Babraham Institute, Cambridge, United Kingdom.
Capucine PicardUniversité Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; INSERM UMR1163, Paris, France; Department of Pediatric Immunology, Hematology and Rheumatology, AP-HP, Necker Children's Hospital, Paris, France; Centre de Référence Déficits Immunitaires Héréditaires, AP-HP, Paris, France; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Imagine Institute, Necker Children's Hospital, Paris, France; St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY.
Sergey NejentsevDepartment of Medicine, University of Cambridge, Cambridge, United Kingdom.
Alison M CondliffeDepartment of Medicine, University of Cambridge, Cambridge, United Kingdom; Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom. Electronic address: a.m.condliffe@sheffield.ac.uk.
Andrew James CantDepartment of Paediatric Immunology, Newcastle upon Tyne hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom.
Délégation Paris 5 · FRNewcastle upon Tyne Hospitals NHS Foundation Trust · GBTrinity College Dublin · IEUniversity Medical Center Freiburg · DEUniversity of Cambridge · GBUniversity of Rome Tor Vergata · ITBabraham Institute · GBChildren's Health Ireland at Crumlin · IERaigmore Hospital · GBRoyal Aberdeen Children's Hospital · GBUniversity Hospital in Motol · CZUniversity of Ulster · GBAddenbrooke's Hospital · GBBarts Health NHS Trust · GBCambridge University Hospitals NHS Foundation Trust · GBCentre National de la Recherche Scientifique · FRCincinnati Children's Hospital Medical Center · USCRUK Lung Cancer Centre of Excellence · GBEpsom and St Helier University Hospitals NHS Trust · GBGreat Ormond Street Hospital for Children NHS Foundation Trust · GB
Funding
Biotechnology and Biological Sciences Research Council BB/I007806/1Biotechnology and Biological Sciences Research Council BBS/E/B/000C0407Biotechnology and Biological Sciences Research Council BBS/E/B/000C0409Cancer Research UK 15965Cancer Research UK C23338/A15965European Research Council 249816Medical Research Council MR/M012328/1Medical Research Council MR/M012328/2Wellcome TrustWellcome Trust 095198/Z/10/ZWellcome Trust 103413/Z/13/Z
Abstract
backgroundActivated phosphoinositide 3-kinase δ syndrome (APDS) is a recently described combined immunodeficiency resulting from gain-of-function mutations in PIK3CD, the gene encoding the catalytic subunit of phosphoinositide 3-kinase δ (PI3Kδ).
objectiveWe sought to review the clinical, immunologic, histopathologic, and radiologic features of APDS in a large genetically defined international cohort.
methodsWe applied a clinical questionnaire and performed review of medical notes, radiology, histopathology, and laboratory investigations of 53 patients with APDS.
resultsRecurrent sinopulmonary infections (98%) and nonneoplastic lymphoproliferation (75%) were common, often from childhood. Other significant complications included herpesvirus infections (49%), autoinflammatory disease (34%), and lymphoma (13%). Unexpectedly, neurodevelopmental delay occurred in 19% of the cohort, suggesting a role for PI3Kδ in the central nervous system; consistent with this, PI3Kδ is broadly expressed in the developing murine central nervous system. Thoracic imaging revealed high rates of mosaic attenuation (90%) and bronchiectasis (60%). Increased IgM levels (78%), IgG deficiency (43%), and CD4 lymphopenia (84%) were significant immunologic features. No immunologic marker reliably predicted clinical severity, which ranged from asymptomatic to death in early childhood. The majority of patients received immunoglobulin replacement and antibiotic prophylaxis, and 5 patients underwent hematopoietic stem cell transplantation. Five patients died from complications of APDS.
conclusionAPDS is a combined immunodeficiency with multiple clinical manifestations, many with incomplete penetrance and others with variable expressivity. The severity of complications in some patients supports consideration of hematopoietic stem cell transplantation for severe childhood disease. Clinical trials of selective PI3Kδ inhibitors offer new prospects for APDS treatment.
Indexed as
AdolescentAdultAnimalsAntibiotic ProphylaxisChildChild, PreschoolClass I Phosphatidylinositol 3-KinasesCohort StudiesEnzyme InhibitorsFemaleHematopoietic Stem Cell TransplantationHerpesviridae InfectionsHumansImmunoglobulins, IntravenousImmunologic Deficiency SyndromesInfantClass I Phosphatidylinositol 3-KinasesEnzyme InhibitorsImmunoglobulins, IntravenousPIK3CD protein, humanActivated phosphoinositide 3-kinase δ syndromebronchiectasishematopoietic stem cell transplantationimmunodeficiencyp110δ-activating mutation causing senescent T cells, lymphadenopathy, and immunodeficiencyphosphoinositide 3-kinase inhibitorphosphoinositide 3-kinase δPIK3CD gene
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Registered trials
NCT03383380ClinicalTrials.gov
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.