{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T02:13:07Z","timestamp":1772244787209,"version":"3.50.1"},"reference-count":13,"publisher":"Georg Thieme Verlag KG","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Klin Padiatr"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Loss or gain-of-function mutations in signal transducer and transcription\n                    activator genes, classified as combined immunodeficiency, can present with\n                    highly heterogeneous and life-threatening clinical presentations. We report an\n                    adolescent girl who has combined immunodeficiency associated with signal\n                    transducer and activator of transcription 3 gain-of-function, c.1032G &gt; C,\n                    p.Met344Ile located in exon 10, identified by a next-generation sequencing panel\n                    performed due to short stature, hepatosplenomegaly, and decreased levels of both\n                    immunoglobulin G and immunoglobulin M. At 12 years of age, the patient was\n                    referred to the pediatric hematology outpatient clinic owing to\n                    hepatosplenomegaly and pancytopenia after initiating growth hormone treatment\n                    due to short stature. On physical examination, bilateral multiple posterior and\n                    anterior cervical micro-lymphadenopathies were detected, her liver was palpated\n                    6 cm below the costal margin, and her spleen was palpated 10 cm below the\n                    costalmargin. The whole blood count revealed a leukocyte count of\n                        2,300\/mm3, neutrophils of 1,330\/mm3, lymphocytes of\n                        730\/mm3, hemoglobin of 8 g\/dL, platelets of\n                    96,000\/mm3, and reticulocytes of 2%. The bone marrow biopsy revealed\n                    a cellularity of 30\u201335%. After steroid-dependent treatment resulted in\n                    Cushing syndrome and treatment with sirolimus was ineffective, treatment with\n                    ruxolitinib 20 mg twice daily significantly resolved cytopenias and\n                    hepatosplenomegaly due to autoimmune lymphoproliferative syndrome.<\/jats:p>","DOI":"10.1055\/a-2788-7908","type":"journal-article","created":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T01:36:06Z","timestamp":1772242566000},"source":"Crossref","is-referenced-by-count":0,"title":["Long-Term Outcomes of Successful Treatment with Ruxolitinib in a\n                    Pediatric Patient with Autoimmune Lymphoproliferative Syndrome and a Signal\n                    Transducer and Activator of Transcription 3 Gain-of-Function\n                    Mutation"],"prefix":"10.1055","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8801-7776","authenticated-orcid":false,"given":"Sultan","family":"Aydin","sequence":"additional","affiliation":[{"name":"Pediatric Hematology and Oncology, Ministry of Health\n                    Antalya Training and Research Hospital, Antalya, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8244-702X","authenticated-orcid":false,"given":"Ayse","family":"Oz","sequence":"additional","affiliation":[{"name":"Pediatric Hematology and Oncology, Ministry of Health\n                    Antalya Training and Research Hospital, Antalya, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tarkan","family":"Kalkan","sequence":"additional","affiliation":[{"name":"Medical Genetics, Ministry of Health Antalya Training\n                    and Research Hospital, Antalya, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00fcney","family":"K\u00fcc\u00fck","sequence":"additional","affiliation":[{"name":"Pediatrics Allergy and Immunology, Ministry of Health\n                    Antalya Training and Research Hospital, Antalya, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatih","family":"Celmeli","sequence":"additional","affiliation":[{"name":"Pediatrics Allergy and Immunology, Ministry of Health\n                    Antalya Training and Research Hospital, Antalya, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1097\/ACI.0000000000000689","article-title":"Primary immune regulatory disorders: a growing universe of immune\n                    dysregulation","volume":"20","author":"A Y Chan","year":"2020","journal-title":"Curr Opin Allergy Clin Immunol"},{"issue":"19","key":"ref2","doi-asserted-by":"crossref","first-page":"4870","DOI":"10.3390\/ijms20194870","article-title":"STAT3 regulates the type I IFN-mediated antiviral response by interfering with\n                    the nuclear entry of STAT1","volume":"20","author":"H Wang","year":"2019","journal-title":"Int J Mol Sci"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/j.jaci.2022.09.002","article-title":"Monogenic early-onset lymphoproliferation and autoimmunity: natural history of\n                    STAT3 gain-of-function syndrome","volume":"151","author":"J W Leiding","year":"2023","journal-title":"J Allergy Clin Immunol"},{"issue":"06","key":"ref4","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1016\/j.jaip.2019.02.018","article-title":"Clinical aspects of STAT3 gain-of-function germline mutations: a systematic\n                    review","volume":"7","author":"A Fabre","year":"2019","journal-title":"J Allergy Clin Immunol Pract"},{"issue":"04","key":"ref5","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1182\/blood-2014-04-570101","article-title":"Autoimmunity, hypogammaglobulinemia, lymphoproliferation, and mycobacterial\n                    disease in patients with activating mutations in STAT3","volume":"125","author":"E M Haapaniemi","year":"2015","journal-title":"Blood"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1007\/s10875-021-01051-1","article-title":"STAT1 Hyper-IgE syndrome-an update and unanswered questions","volume":"41","author":"C Tsilifis","year":"2021","journal-title":"J Clin Immunol"},{"issue":"03","key":"ref7","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1111\/cei.13625","article-title":"Novel STAT-3 gain-of-function variant with hypogammaglobulinemia and recurrent\n                    infection phenotype","volume":"205","author":"M Erdos","year":"2021","journal-title":"Clin Exp Immunol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"108316","DOI":"10.1016\/j.clim.2019.108316","article-title":"Distinct molecular response patterns of activating STAT3 mutations associate\n                    with penetrance of lymphoproliferation and autoimmunity","volume":"210","author":"S Jagle","year":"2020","journal-title":"Clin Immunol"},{"issue":"04","key":"ref9","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1182\/blood-2014-09-602763","article-title":"Early-onset lymphoproliferation and autoimmunity caused by germline STAT3\n                    gain-of-function mutations","volume":"125","author":"J D Milner","year":"2015","journal-title":"Blood"},{"issue":"08","key":"ref10","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1038\/ng.3040","article-title":"Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune\n                    disease","volume":"46","author":"S E Flanagan","year":"2014","journal-title":"Nat Genet"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"770077","DOI":"10.3389\/fped.2022.770077","article-title":"STAT3 gain-of-function syndrome","volume":"10","author":"T P Vogel","year":"2023","journal-title":"Front Pediatr"},{"issue":"05","key":"ref12","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1016\/j.jaci.2018.07.020","article-title":"Jakinibs for the treatment of immune dysregulation in patients with\n                    gain-of-function signal transducer and activator of transcription 1 (STAT1) or\n                    STAT3 mutations","volume":"142","author":"L R Forbes","year":"2018","journal-title":"J Allergy Clin Immunol"},{"issue":"01","key":"ref13","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.jaci.2023.10.018","article-title":"JAK inhibitor treatment for inborn errors of JAK\/STAT signaling: An\n                    ESID\/EBMT-IEWP retrospective study","volume":"153","author":"M Fischer","year":"2024","journal-title":"J Allergy Clin Immunol"}],"container-title":["Klinische P\u00e4diatrie"],"original-title":[],"language":"de","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2788-7908.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T01:36:08Z","timestamp":1772242568000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2788-7908"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,27]]},"references-count":13,"URL":"https:\/\/doi.org\/10.1055\/a-2788-7908","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0300-8630","1439-3824"],"issn-type":[{"value":"0300-8630","type":"print"},{"value":"1439-3824","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,27]]}}}