Research & Literature

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

Singer M, Deutschman CS, Seymour CW, et al.

JAMA 2016; (315(8)):801-10 doi:10.1001/jama.2016.0287.

Activated PI3Kδ syndrome type 2: Two patients, a novel mutation, and review of the literature.

Olbrich P, Lorenz M, Cura Daball P, et al.

Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 2016; (27(6)):640-4 doi:10.1111/pai.12585.

Clinical and immunologic phenotype associated with activated phosphoinositide 3-kinase δ syndrome 2: A cohort study.

Elkaim E, Neven B, Bruneau J, et al.

The Journal of allergy and clinical immunology 2016; (138(1)):210-218.e9 doi:10.1016/j.jaci.2016.03.022.

Clinical spectrum and features of activated phosphoinositide 3-kinase δ syndrome: A large patient cohort study.

Coulter TI, Chandra A, Bacon CM, et al.

The Journal of allergy and clinical immunology 2017; (139(2)):597-606.e4 doi:10.1016/j.jaci.2016.06.021.

Conformational disruption of PI3Kδ regulation by immunodeficiency mutations in PIK3CD and PIK3R1.

Dornan GL, Siempelkamp BD, Jenkins ML, et al.

Proceedings of the National Academy of Sciences of the United States of America 2017; (114(8)):1982-1987 doi:10.1073/pnas.1617244114.

Effective "activated PI3Kδ syndrome"-targeted therapy with the PI3Kδ inhibitor leniolisib.

Rao VK, Webster S, Dalm VASH, et al.

Blood 2017; (130(21)):2307-2316 doi:10.1182/blood-2017-08-801191.

Respiratory Manifestations of the Activated Phosphoinositide 3-Kinase Delta Syndrome.

Condliffe AM, Chandra A

Frontiers in immunology 2018; (9()):338 doi:10.3389/fimmu.2018.00338.

Exhaustion of the CD8+ T Cell Compartment in Patients with Mutations in Phosphoinositide 3-Kinase Delta.

Wentink MWJ, Mueller YM, Dalm VASH, et al.

Frontiers in immunology 2018; (9()):446 doi:10.3389/fimmu.2018.00446.

Disease Evolution and Response to Rapamycin in Activated Phosphoinositide 3-Kinase δ Syndrome: The European Society for Immunodeficiencies-Activated Phosphoinositide 3-Kinase δ Syndrome Registry.

Maccari ME, Abolhassani H, Aghamohammadi A, et al.

Frontiers in immunology 2018; (9()):543 doi:10.3389/fimmu.2018.00543.

Enhanced AKT Phosphorylation of Circulating B Cells in Patients With Activated PI3Kδ Syndrome.

Asano T, Okada S, Tsumura M, et al.

Frontiers in immunology 2018; (9()):568 doi:10.3389/fimmu.2018.00568.

Activating PIK3CD mutations impair human cytotoxic lymphocyte differentiation and function and EBV immunity.

Edwards ESJ, Bier J, Cole TS, et al.

The Journal of allergy and clinical immunology 2019; (143(1)):276-291.e6 doi:10.1016/j.jaci.2018.04.030.

Germline-activating mutations in PIK3CD compromise B cell development and function.

Avery DT, Kane A, Nguyen T, et al.

The Journal of experimental medicine 2018; (215(8)):2073-2095 doi:10.1084/jem.20180010.

Genetic Defects in Phosphoinositide 3-Kinase δ Influence CD8+ T Cell Survival, Differentiation, and Function.

Cannons JL, Preite S, Kapnick SM, et al.

Frontiers in immunology 2018; (9()):1758 doi:10.3389/fimmu.2018.01758.

CYP3A but not P-gp plays a relevant role in the in vivo intestinal and hepatic clearance of the delta-specific phosphoinositide-3 kinase inhibitor leniolisib.

De Buck S, Kucher K, Hara H, et al.

Biopharmaceutics & drug disposition 2018; (39(8)):394-402 doi:10.1002/bdd.2157.

Activated PIK3CD drives innate B cell expansion yet limits B cell-intrinsic immune responses.

Wray-Dutra MN, Al Qureshah F, Metzler G, et al.

The Journal of experimental medicine 2018; (215(10)):2485-2496 doi:10.1084/jem.20180617.

Report of a Chinese Cohort with Activated Phosphoinositide 3-Kinase δ Syndrome.

Wang Y, Wang W, Liu L, et al.

Journal of clinical immunology 2018; (38(8)):854-863 doi:10.1007/s10875-018-0568-x.

Evaluation of Lymphoproliferative Disease and Increased Risk of Lymphoma in Activated Phosphoinositide 3 Kinase Delta Syndrome: A Case Report With Discussion.

Pham MN, Cunningham-Rundles C

Frontiers in pediatrics 2018; (6()):402 doi:10.3389/fped.2018.00402.

Advances in the Study of Chronic Active Epstein-Barr Virus Infection: Clinical Features Under the 2016 WHO Classification and Mechanisms of Development.

Arai A

Frontiers in pediatrics 2019; (7()):14 doi:10.3389/fped.2019.00014.

A Rare Case of Activated Phosphoinositide 3-Kinase Delta Syndrome (APDS) Presenting With Hemophagocytosis Complicated With Hodgkin Lymphoma.

Cansever M, Zietara N, Chiang SCC, et al.

Journal of pediatric hematology/oncology 2020; (42(2)):156-159 doi:10.1097/MPH.0000000000001487.

Clinical, Immunological, and Genetic Features in Patients with Activated PI3Kδ Syndrome (APDS): a Systematic Review.

Jamee M, Moniri S, Zaki-Dizaji M, et al.

Clinical reviews in allergy & immunology 2020; (59(3)):323-333 doi:10.1007/s12016-019-08738-9.

Successful Sirolimus Treatment for Korean Patients with Activated Phosphoinositide 3-kinase δ Syndrome 1: the First Case Series in Korea.

Kang JM, Kim SK, Kim D, et al.

Yonsei medical journal 2020; (61(6)):542-546 doi:10.3349/ymj.2020.61.6.542.

Evaluation of B-cell intracellular signaling by monitoring the PI3K-Akt axis in patients with common variable immunodeficiency and activated phosphoinositide 3-kinase delta syndrome.

Del Pino-Molina L, Torres Canizales JM, Rodríguez-Pena R, López-Granados E

Cytometry. Part B, Clinical cytometry 2021; (100(4)):460-466 doi:10.1002/cyto.b.21956.

Accuracy of a Modified qSOFA Score for Predicting Critical Care Admission in Febrile Children.

Romaine ST, Potter J, Khanijau A, et al.

Pediatrics 2020; (146(4)) doi:10.1542/peds.2020-0782.

Seletalisib for Activated PI3Kδ Syndromes: Open-Label Phase 1b and Extension Studies.

Diaz N, Juarez M, Cancrini C, et al.

Journal of immunology (Baltimore, Md. : 1950) 2020; (205(11)):2979-2987 doi:10.4049/jimmunol.2000326.

Updates on pediatric sepsis.

Cruz AT, Lane RD, Balamuth F, et al.

Journal of the American College of Emergency Physicians open 2020; (1(5)):981-993 doi:10.1002/emp2.12173.

Hemophagocytic Lymphohistiocytosis in the Emergency Department: Recognizing and Evaluating a Hidden Threat.

Morrissette K, Bridwell R, Lentz S, et al.

The Journal of emergency medicine 2021; (60(6)):743-751 doi:10.1016/j.jemermed.2021.02.006.

International retrospective study of allogeneic hematopoietic cell transplantation for activated PI3K-delta syndrome.

Dimitrova D, Nademi Z, Maccari ME, et al.

The Journal of allergy and clinical immunology 2022; (149(1)):410-421.e7 doi:10.1016/j.jaci.2021.04.036.

Infections in activated PI3K delta syndrome (APDS).

Brodsky NN, Lucas CL

Current opinion in immunology 2021; (72()):146-157 doi:10.1016/j.coi.2021.04.010.

Natural Course of Activated Phosphoinositide 3-Kinase Delta Syndrome in Childhood and Adolescence.

Bloomfield M, Klocperk A, Zachova R, et al.

Frontiers in pediatrics 2021; (9()):697706 doi:10.3389/fped.2021.697706.

Clinical Manifestations and Outcomes of Activated Phosphoinositide 3-Kinase δ Syndrome from the USIDNET Cohort.

Oh J, Garabedian E, Fuleihan R, Cunningham-Rundles C

The journal of allergy and clinical immunology. In practice 2021; (9(11)):4095-4102 doi:10.1016/j.jaip.2021.07.044.

Phenotypic characterization of patients with activated PI3Kδ syndrome 1 presenting with features of systemic lupus erythematosus.

Wang Y, Yang Q, Chen X, et al.

Genes & diseases 2021; (8(6)):907-917 doi:10.1016/j.gendis.2020.04.012.

Case Report: EBV Chronic Infection and Lymphoproliferation in Four APDS Patients: The Challenge of Proper Characterization, Therapy, and Follow-Up.

Rivalta B, Amodio D, Milito C, et al.

Frontiers in pediatrics 2021; (9()):703853 doi:10.3389/fped.2021.703853.

Consensus-Based Guidelines for the Recognition, Diagnosis, and Management of Hemophagocytic Lymphohistiocytosis in Critically Ill Children and Adults.

Hines MR, von Bahr Greenwood T, Beutel G, et al.

Critical care medicine 2022; (50(5)):860-872 doi:10.1097/CCM.0000000000005361.

Predictor of Early Administration of Antibiotics and a Volume Resuscitation for Young Infants with Septic Shock.

Nomura O, Ihara T, Morikawa Y, et al.

Antibiotics (Basel, Switzerland) 2021; (10(11)) doi:10.3390/antibiotics10111414.

Dysregulated PI3K Signaling in B Cells of CVID Patients.

Harder I, Münchhalfen M, Andrieux G, et al.

Cells 2022; (11(3)) doi:10.3390/cells11030464.

Activated Phosphoinositide 3-Kinase δ Syndrome: a Large Pediatric Cohort from a Single Center in China.

Qiu L, Wang Y, Tang W, et al.

Journal of clinical immunology 2022; (42(4)):837-850 doi:10.1007/s10875-022-01218-4.

A randomized, placebo-controlled phase 3 trial of the PI3Kδ inhibitor leniolisib for activated PI3Kδ syndrome.

Rao VK, Webster S, Šedivá A, et al.

Blood 2023; (141(9)):971-983 doi:10.1182/blood.2022018546.

Human PIK3R1 mutations disrupt lymphocyte differentiation to cause activated PI3Kδ syndrome 2.

Nguyen T, Lau A, Bier J, et al.

The Journal of experimental medicine 2023; (220(6)) doi:10.1084/jem.20221020.

Leniolisib: First Approval.

Duggan S, Al-Salama ZT

Drugs 2023; (83(10)):943-948 doi:10.1007/s40265-023-01895-4.

Activated phosphoinositide 3-kinase δ syndrome: Update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity.

Maccari ME, Wolkewitz M, Schwab C, et al.

The Journal of allergy and clinical immunology 2023; (152(4)):984-996.e10 doi:10.1016/j.jaci.2023.06.015.

Activated phosphoinositide 3-kinase δ syndrome caused by PIK3CD mutations: expanding the phenotype.

Zhao P, Huang J, Fu H, et al.

Pediatric rheumatology online journal 2024; (22(1)):24 doi:10.1186/s12969-024-00955-7.

The Dark Side of Activated Phosphoinositide 3-Kinase-δ Syndrome 2: A Story Rewritten through FDG-PET.

Catelli A, Nanni C, Mulè R, et al.

Journal of clinical medicine 2024; (13(8)) doi:10.3390/jcm13082203.

A qualitative study to explore the burden of disease in activated phosphoinositide 3-kinase delta syndrome (APDS).

Hitchcock I, Skrobanski H, Matter E, et al.

Orphanet journal of rare diseases 2024; (19(1)):203 doi:10.1186/s13023-024-03215-9.

Flow cytometry-based diagnostic approach for inborn errors of immunity: experience from Algeria.

Tahiat A, Belbouab R, Yagoubi A, et al.

Frontiers in immunology 2024; (15()):1402038 doi:10.3389/fimmu.2024.1402038.

Case report on activated PI3K-delta syndrome.

Crisanto-López IE, Pérez-Arzola AA, Hernández-Castañeda Y, et al.

Boletin medico del Hospital Infantil de Mexico 2024; (81(4)):245-249 doi:10.24875/BMHIM.23000124.

A single center experience on PI3K/AKT/MTOR signaling defects: Towards pathogenicity assessment for four novel defects.

Bildik HN, Esenboga S, Halaclı SO, et al.

Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 2024; (35(9)):e14245 doi:10.1111/pai.14245.

Technical challenges of intracellular flow cytometry-based assays as a functional complement to diagnosis of signaling defects of inborn errors of immunity: PI3K pathway as a case of study.

Del Pino Molina L, Reche Yebra K, Soto Serrano Y, et al.

Frontiers in immunology 2024; (15()):1476218 doi:10.3389/fimmu.2024.1476218.

Genetic Etiologies and Outcomes in Malignancy and Mortality in Activated Phosphoinositide 3-Kinase Delta Syndrome: A Systematic Review.

Büsch K, Memmott HL, McLaughlin HM, et al.

Advances in therapy 2025; (42(2)):752-771 doi:10.1007/s12325-024-03066-7.

Case Report: Early-onset or recalcitrant cytopenias as presenting manifestations of activated PI3Kδ syndrome.

Remiker AS, Lopes JPM, Jesudas R, et al.

Frontiers in pediatrics 2024; (12()):1494945 doi:10.3389/fped.2024.1494945.

Hyperactivation of the PI3K pathway in inborn errors of immunity: current understanding and therapeutic perspectives.

IJspeert H, Dalm VASH, van Zelm MC, Edwards ESJ

Immunotherapy advances 2024; (4(1)):ltae009 doi:10.1093/immadv/ltae009.

Report of the Italian Cohort with Activated Phosphoinositide 3-Kinase δ Syndrome in the Target Therapy Era.

Barzaghi F, Moratti M, Panza G, et al.

Journal of clinical immunology 2024; (45(1)):58.

Atypical lymphoproliferations associated with germline genetic variants: a report of the 2024 EA4HP/SH lymphoma workshop.

van den Brand M, Rásó-Barnett L, Gasljevic G, et al.

Virchows Archiv : an international journal of pathology 2025; (487(2)):275-286 doi:10.1007/s00428-025-04189-0.

Activated PI3K-δ syndrome presenting with cervical lymphadenopathy in a pediatric patient: a case report and review of the literature.

Huang Z, Wang Y, Wei R, et al.

Frontiers in immunology 2025; (16()):1622764 doi:10.3389/fimmu.2025.1622764.

Key outcomes in treatment of activated phosphoinositide 3-kinase delta syndrome: An e-Delphi panel study and responder threshold application.

Upton JEM, Williams KW, Cant A, et al.

PloS one 2025; (20(10)):e0333341 doi:10.1371/journal.pone.0333341.

Systemic Chronic Active Epstein-Barr Virus Disease.

Shannon-Lowe C

Current topics in microbiology and immunology 2025; doi:10.1007/82_2025_336.

Activated PI3Kδ syndrome in inborn errors of immunity: diagnostic strategies and clinical challenges.

Bozkurt S, Ozturk N, Altunbas MY, et al.

Frontiers in immunology 2025; (16()):1735023 doi:10.3389/fimmu.2025.1735023.

Phosphoinositide 3-kinase δ activity in patients with systemic lupus erythematosus.

Mirfazeli ES, Kharkar S, Tsang-A-Sjoe MWP, et al.

Frontiers in immunology 2026; (17()):1745692 doi:10.3389/fimmu.2026.1745692.

Diagnostic odyssey of patients with the rare immunodeficiency activated PI3 kinase delta syndrome (APDS): case study from expert and patient surveys.

Wolf HM, Candotti F, Spelsberg R, et al.

Frontiers in immunology 2026; (17()):1763482 doi:10.3389/fimmu.2026.1763482.

Case Report: Recurrent pulmonary infections with neck masses: a diagnostic challenge and literature review.

Zhao L, Zhao J, Lu Y

Frontiers in medicine 2026; (13()):1807946 doi:10.3389/fmed.2026.1807946.

Shrinking Spleens and Nodes, Expanding Horizons: Leniolisib and the Future of Activated Phosphoinositide 3-Kinase Delta Syndrome.

Visitsunthorn K, Rao VK

The journal of allergy and clinical immunology. In practice 2026; (14(7)):1525-1528 doi:10.1016/j.jaip.2026.03.040.

Clinical and immunological spectrum of five patients with activated phosphoinositide 3-kinase δ syndrome 1: A multicentric study from India.

Bhattad S, Singh N, Mohite RS, et al.

Journal of human immunity 2026; (2(4)):e20250251 doi:10.70962/jhi.20250251.

How I treat: Diagnostic clues and treatment for activated phosphoinositide 3-kinase delta syndrome.

Kanegane H, Tomomasa D, Okada S

Journal of human immunity 2026; (2(5)):e20260054 doi:10.70962/jhi.20260054.

Epstein-Barr Virus-Positive B-Cell Lymphoproliferative Disorder Complicated by Septic Shock in Activated PI3Kδ Syndrome: A Pediatric Case Report and Literature Review.

Zhao X, Ming X, Shang Z, et al.

Case reports in hematology 2026; (2026()):3644513 doi:10.1155/crh/3644513.