{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:36:17Z","timestamp":1791246977548,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T00:00:00Z","timestamp":1616457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The primary immunodeficiency syndromes of cytotoxic T lymphocyte\u2010associated protein 4 (CTLA\u20104) haploinsufficiency and lipopolysaccharide\u2010responsive and beige\u2010like anchor protein (LRBA) deficiency present with multisystem immune dysregulation. The aim of this study was to characterize and compare the pulmonary manifestations of these two diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrospectively analyzed the pulmonary clinical, radiologic, and histopathologic characteristics of six patients with CTLA\u20104 haploinsufficiency and four patients with LRBA deficiency with pulmonary involvement followed at a large tertiary care center.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Chronic respiratory symptoms were more frequent in patients with LRBA deficiency versus CTLA\u20104 haploinsufficiency (3\/4 vs. 1\/6). Cough was the most common respiratory symptom. Abnormalities in pulmonary exam and pulmonary function testing were more frequent in LRBA deficiency (4\/4, 2\/4) compared to CTLA\u20104 haploinsufficiency (1\/6, 2\/6). Chest computed tomography (CT) findings included mediastinal lymphadenopathy (4\/4 in LRBA deficiency vs. 1\/4 in CTLA\u20104 haploinsufficiency), pulmonary nodules (4\/4, 3\/4), ground\u2010glass opacification (4\/4, 3\/4), and bronchiectasis (3\/4, 1\/4). Lymphocytic inflammation, concentrated bronchovasculocentrically and paraseptally, was the predominant pathologic finding and was observed in all patients who had lung biopsies (<jats:italic>N<\/jats:italic>\u2009=\u20093 with LRBA deficiency; <jats:italic>N<\/jats:italic>\u2009=\u20093 with CTLA\u20104 haploinsufficiency).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Despite phenotypic overlap amongst these diseases, LRBA deficiency demonstrated greater severity of pulmonary disease, indicated by respiratory symptoms, pulmonary exam, and intrathoracic radiologic findings. Chest CT was the most sensitive indicator of pulmonary involvement in both disorders. Lymphocytic inflammation is the key histologic feature of both disorders. Pediatric pulmonologists should consider these disorders of immune dysregulation in the relevant clinical context to provide earlier diagnosis, comprehensive pulmonary evaluation and treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ppul.25373","type":"journal-article","created":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T10:40:34Z","timestamp":1615545634000},"page":"2232-2241","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Pulmonary manifestations of immune dysregulation in CTLA\u20104 haploinsufficiency and LRBA deficiency"],"prefix":"10.1002","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5008-3121","authenticated-orcid":false,"given":"Katie A.","family":"Krone","sequence":"first","affiliation":[{"name":"Division of Pulmonary Medicine,\u00a0Boston Children's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbey J.","family":"Winant","sequence":"additional","affiliation":[{"name":"Department of Radiology,\u00a0Boston Children's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara O.","family":"Vargas","sequence":"additional","affiliation":[{"name":"Department of Pathology,\u00a0Boston Children's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig D.","family":"Platt","sequence":"additional","affiliation":[{"name":"Division of Immunology,\u00a0Boston Children's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M.","family":"Bartnikas","sequence":"additional","affiliation":[{"name":"Division of Immunology,\u00a0Boston Children's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Janssen","sequence":"additional","affiliation":[{"name":"Division of Immunology,\u00a0Boston Children's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Lillehei","sequence":"additional","affiliation":[{"name":"Department of Surgery,\u00a0Boston Children's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8453-4920","authenticated-orcid":false,"given":"Edward Y.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Radiology,\u00a0Boston Children's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha P.","family":"Fishman","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine,\u00a0Boston Children's Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3566-9690","authenticated-orcid":false,"given":"Alicia","family":"Casey","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine,\u00a0Boston Children's Hospital Harvard Medical School  Boston Massachusetts 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