{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:40:37Z","timestamp":1785415237296,"version":"3.56.0"},"reference-count":13,"publisher":"Rockefeller University Press","issue":"4","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7,6]]},"abstract":"<jats:p>Activated phosphoinositide 3-kinase \u03b4 syndrome 1 (APDS1) is a combined immunodeficiency caused by monoallelic gain-of-function mutations in the PIK3CD gene. Patients with APDS1 have significant sinopulmonary involvement, lymphoproliferation, and autoimmune manifestations. We analyzed the clinical profile, treatment, and outcomes of five patients with APDS1. A total of 556 patients were diagnosed with inborn errors of immunity at our center between February 2017 and October 2025. Five patients had APDS1, confirmed by next-generation sequencing. Their records were analyzed in detail. The male-to-female ratio was 4:1. The mean age at symptom onset and at diagnosis was 14.8 and 62 mo, respectively. The age at onset of infections (mean age: 26 mo) preceded lymphoproliferation (mean age: 36 mo). Sinopulmonary infections (n = 3), recurrent gastroenteritis (n = 2), oral candidiasis (n = 1), and meningoencephalitis (n = 1) were the most commonly noted infections. Lymphoproliferation was seen in four patients, the most common being cervical lymph node enlargement (n = 4), followed by adenotonsillar hypertrophy (n = 3) and chronic splenomegaly (n = 3). Three of these patients with lymphoproliferation had Epstein-Barr viremia. Inflammatory colitis (n = 1) was the sole autoimmune manifestation noted in our cohort. Lymphocyte subset analysis showed increased CD8 cells and a reversal of the CD4:CD8 ratio (n = 4). Therapy included antibiotic prophylaxis (n = 5), intravenous immunoglobulin replacement therapy (n = 3), steroids (n = 3), mycophenolate mofetil (n = 1), and sirolimus (n = 1). Presently, four patients are alive and doing well, while one child is lost to follow-up. To the best of our knowledge, this is the first case series of APDS1 from the Indian subcontinent. We observed a significant delay in the diagnosis of these patients highlighting the need for raising awareness regarding this entity among pediatricians and primary care physicians.<\/jats:p>","DOI":"10.70962\/jhi.20250251","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T06:22:07Z","timestamp":1774678927000},"update-policy":"https:\/\/doi.org\/10.70962\/jhi.crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical and immunological spectrum of five patients with activated phosphoinositide 3-kinase \u03b4 syndrome 1: A multicentric study from India"],"prefix":"10.70962","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5048-9727","authenticated-orcid":true,"given":"Sagar","family":"Bhattad","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05mryn396","id-type":"ROR","asserted-by":"publisher"}],"name":"Paediatric Immunology, Rheumatology and Bone Marrow Transplant, Manipal Hospital 1 , Bangalore,","place":["India"]},{"name":"Aster CMI Hospital 2 , Bangalore,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8467-2290","authenticated-orcid":true,"given":"Neha","family":"Singh","sequence":"additional","affiliation":[{"name":"ESIC Medical College and Hospital 3 Department of Paediatrics, , Ranchi,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0675-8608","authenticated-orcid":true,"given":"Rachna S.","family":"Mohite","sequence":"additional","affiliation":[{"name":"Paediatric Immunology and Rheumatology, Sai Child Care Hospital 4 , Navi Mumbai,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7720-850X","authenticated-orcid":true,"given":"Jyothi","family":"Janardhanan","sequence":"additional","affiliation":[{"name":"Paediatric Immunology and Rheumatology, Aster MIMS 5 , Kannur,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9980-7143","authenticated-orcid":true,"given":"Srikanta","family":"J.T.","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05mryn396","id-type":"ROR","asserted-by":"publisher"}],"name":"Allergy and Sleep Medicine, Manipal Hospital 6 Department of Paediatric Pulmonology, , Bangalore,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9223-6763","authenticated-orcid":true,"given":"Anuj","family":"Shukla","sequence":"additional","affiliation":[{"name":"Niruj Rheumatology Clinic 7 , Ahmedabad,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6958-0859","authenticated-orcid":true,"given":"Srinivas","family":"Jakka","sequence":"additional","affiliation":[{"name":"Ankura Children\u2019s Hospitals 8 Department of Paediatrics, , Hyderabad,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3520-9085","authenticated-orcid":true,"given":"Ranjit B.","family":"Joseph","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05rx18c05","id-type":"ROR","asserted-by":"publisher"}],"name":"Aster Medcity 9 Department of Paediatrics, , Kochi,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"2026042109074269000_bib1","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1126\/science.1243292","article-title":"Phosphoinositide 3-kinase \u03b4 gene mutation predisposes to respiratory infection and airway damage","volume":"342","author":"Angulo","year":"2013","journal-title":"Science"},{"key":"2026042109074269000_bib2","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/ni.2771","article-title":"Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110\u03b4 result in T cell senescence and human immunodeficiency","volume":"15","author":"Lucas","year":"2014","journal-title":"Nat. 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