{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T03:25:54Z","timestamp":1793244354301,"version":"4.5.0"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T00:00:00Z","timestamp":1752019200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p>Autosomal dominant gain-of-function (GOF) variants in the signal transducer and activator of transcription 3 (<jats:italic>STAT3<\/jats:italic>) result in an inborn error of immunity characterized by multi-organ autoimmunity and lymphoproliferation. In this study, we retrospectively analyzed a rare case of <jats:italic>STAT3<\/jats:italic> GOF mutation with thrombocytopenia, immunoglobulin deficiency, and recurrent respiratory infections. Whole-exome sequencing revealed a heterozygous mutation (c. 2144C\u2009&amp;gt;\u2009T, p. P715l) in the <jats:italic>STAT3<\/jats:italic> gene. The patient initially received only anti-infective and immunoglobulin-supportive therapies at an external hospital, which proved unsatisfactory. Over time, the patient developed severe interstitial lung disease (ILD) and arthritis, which were effectively managed with tocilizumab at our hospital. This case underscores the importance of early diagnosis and timely initiation of biological therapy for the management of ILD with <jats:italic>STAT3<\/jats:italic> GOF mutations.<\/jats:p>","DOI":"10.3389\/fped.2025.1577746","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T05:46:53Z","timestamp":1752126413000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Successful anti-IL-6 treatment for interstitial lung disease associated with STAT3 gain-of-function: a case report and literature review"],"prefix":"10.3389","volume":"13","author":[{"given":"Peng","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meifang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhidan","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiguo","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"770077","DOI":"10.3389\/fped.2022.770077","article-title":"STAT3 gain-of-function syndrome","volume":"10","author":"Vogel","year":"2022","journal-title":"Front Pediatr"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1400348","DOI":"10.3389\/fimmu.2024.1400348","article-title":"JAK inhibitors to treat STAT3 gain-of-function: a single-center report and literature review","volume":"15","author":"Atschekzei","year":"2024","journal-title":"Front Immunol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e2407","DOI":"10.1002\/mgg3.2407","article-title":"A novel gain-of-function STAT3 variant in infantile-onset diabetes associated with multiorgan autoimmunity","volume":"12","author":"Zhou","year":"2024","journal-title":"Mol Genet Genomic Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1016\/j.jaci.2019.11.042","article-title":"Erythropoiesis defect observed in STAT3 GOF patients with severe anemia","volume":"145","author":"Mauracher","year":"2020","journal-title":"J Allergy Clin Immunol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"866638","DOI":"10.3389\/fimmu.2022.866638","article-title":"A novel STAT3 gain-of-function mutation in fatal infancy-onset interstitial lung disease","volume":"13","author":"Deng","year":"2022","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1111\/cei.13625","article-title":"Novel STAT-3 gain-of-function variant with hypogammaglobulinemia and recurrent infection phenotype","volume":"205","author":"Erd\u0151s","year":"2021","journal-title":"Clin Exp Immunol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1016\/j.jaci.2022.09.002","article-title":"Monogenic early-onset lymphoproliferation and autoimmunity: natural history of STAT3 gain-of-function syndrome","volume":"151","author":"Leiding","year":"2023","journal-title":"J Allergy Clin Immunol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1958","DOI":"10.1016\/j.jaip.2019.02.018","article-title":"Clinical aspects of STAT3 gain-of-function germline mutations: a systematic review","volume":"7","author":"Fabre","year":"2019","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B9","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1007\/s10875-020-00914-3","article-title":"Life-saving, dose-adjusted, targeted therapy in a patient with a STAT3 gain-of-function mutation","volume":"41","author":"Sarfati","year":"2021","journal-title":"J Clin Immunol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.1038\/jid.2012.499","article-title":"The IL-6 trans-signaling-STAT3 pathway mediates ECM and cellular proliferation in fibroblasts from hypertrophic scar","volume":"133","author":"Ray","year":"2013","journal-title":"J Invest Dermatol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1164\/rccm.201906-1204LE","article-title":"Successful treatment of interstitial lung disease in STAT3 gain-of-function using JAK inhibitors","volume":"202","author":"Silva-Carmona","year":"2020","journal-title":"Am J Respir Crit Care Med"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1665","DOI":"10.1016\/j.jaci.2018.07.020","article-title":"Jakinibs for the treatment of immune dysregulation in patients with gain-of-function signal transducer and activator of transcription 1 (STAT1) or STAT3 mutations","volume":"142","author":"Forbes","year":"2018","journal-title":"J Allergy Clin Immunol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1182\/blood-2014-09-602763","article-title":"Early-onset lymphoproliferation and autoimmunity caused by germline STAT3 gain-of-function mutations","volume":"125","author":"Milner","year":"2015","journal-title":"Blood"},{"key":"B14","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1159\/000456544","article-title":"Short stature in a boy with multiple early-onset autoimmune conditions due to a STAT3 activating mutation: could intracellular growth hormone signalling be compromised?","volume":"88","author":"Sediva","year":"2017","journal-title":"Horm Res Paediatr"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2347","DOI":"10.1172\/JCI122462","article-title":"TGF-\u03b2\u2013induced epigenetic deregulation of SOCS3 facilitates STAT3 signaling to promote fibrosis","volume":"130","author":"Dees","year":"2020","journal-title":"J Clin Invest"},{"key":"B16","doi-asserted-by":"publisher","first-page":"110979","DOI":"10.1016\/j.mce.2020.110979","article-title":"Activating mutations of STAT3: impact on human growth","volume":"518","author":"Guti\u00e9rrez","year":"2020","journal-title":"Mol Cell Endocrinol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"i4","DOI":"10.1093\/rheumatology\/key432","article-title":"Janus kinases to jakinibs: from basic insights to clinical practice","volume":"58","author":"Gadina","year":"2019","journal-title":"Rheumatology"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1016\/j.immuni.2019.03.026","article-title":"Targeting interleukin-6 signaling in clinic","volume":"50","author":"Kang","year":"2019","journal-title":"Immunity"},{"key":"B19","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1016\/j.bj.2021.03.003","article-title":"Germline STAT3 gain-of-function mutations in primary immunodeficiency: impact on the cellular and clinical phenotype","volume":"44","author":"Faletti","year":"2021","journal-title":"Biomed J"},{"key":"B20","doi-asserted-by":"publisher","first-page":"671755","DOI":"10.3389\/fimmu.2021.671755","article-title":"Primary immune regulatory disorders with an autoimmune lymphoproliferative syndrome-like phenotype: immunologic evaluation, early diagnosis and management","volume":"12","author":"L\u00f3pez-Nevado","year":"2021","journal-title":"Front Immunol"},{"key":"B21","article-title":"Allogeneic Hematopoietic Stem Cell Transplantation for Congenital Immune Dysregulatory Disorders [2296\u20132360 (Print)]","author":"Bakhtiar","year":""},{"key":"B22","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1177\/1093526620980615","article-title":"Pulmonary histopathology findings in patients with STAT3 gain of function syndrome","volume":"24","author":"Cortes-Santiago","year":"2021","journal-title":"Pediatr Dev Pathol"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2025.1577746\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T13:38:50Z","timestamp":1752154730000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2025.1577746\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,9]]},"references-count":22,"alternative-id":["10.3389\/fped.2025.1577746"],"URL":"https:\/\/doi.org\/10.3389\/fped.2025.1577746","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,9]]},"article-number":"1577746"}}