{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T16:20:54Z","timestamp":1787934054338,"version":"build-2784847793"},"reference-count":14,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T00:00:00Z","timestamp":1610668800000},"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. Immunol."],"abstract":"<jats:p><jats:italic>STAT3<\/jats:italic> gain-of-function (GOF) mutations can be responsible for an incomplete phenotype mainly characterized by hematological autoimmunity, even in the absence of other organ autoimmunity, growth impairment, or severe infections. We hereby report a case with an incomplete form of <jats:italic>STAT3<\/jats:italic> GOF intensified by a concomitant hereditary hematological disease, which misleads the diagnosis. The patient presented with lymphadenopathy, splenomegaly, hypogammaglobulinemia, and severe autoimmune hemolytic anemia (AIHA) with critical complications, including stroke. A Primary Immune Regulatory Disorders (PIRD) was suspected, and molecular analysis revealed a <jats:italic>de novo STAT3<\/jats:italic> gain-of-function mutation. The response to multiple immune suppressive treatments was ineffective, and further investigations revealed a spectrin deficiency. Ultimately, hematopoietic stem cell transplantation from a matched unrelated donor was able to cure the patient. Our case shows an atypical presentation of <jats:italic>STAT3<\/jats:italic> GOF associated with hereditary spherocytosis, and how achievement of a good long-term outcome depends on a strict clinical and laboratory monitoring, as well as on prompt therapeutic intervention.<\/jats:p>","DOI":"10.3389\/fimmu.2020.620046","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T04:17:41Z","timestamp":1610684261000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Case Report: Signal Transducer and Activator of Transcription 3 Gain-of-Function and Spectrin Deficiency: A Life-Threatening Case of Severe Hemolytic Anemia"],"prefix":"10.3389","volume":"11","author":[{"given":"Sara","family":"Ciullini Mannurita","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rayan","family":"Goda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebe","family":"Schiavo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Luisa","family":"Coniglio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annachiara","family":"Azzali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Fotzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Tondo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Tintori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Frenos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Chiara","family":"Sanvito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Vignoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Luceri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Bigagli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Grassi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario Milco","family":"D\u2019Elios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Favre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Gambineri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,15]]},"reference":[{"key":"B1","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\u00a0Allergy Clin Immunol Pract"},{"key":"B2","doi-asserted-by":"publisher","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":"B3","doi-asserted-by":"publisher","DOI":"10.1159\/000486229","article-title":"Molecular Genetic Mechanisms of Hereditary Spherocytosis: Current Perspectives","volume":"139","author":"He","year":"2018","journal-title":"Acta Haematol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2013.04.003","article-title":"Hereditary spherocytosis, elliptocytosis, and other red cell membrane disorders","volume":"27","author":"Da Costa","year":"2013","journal-title":"Blood Rev"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30","article-title":"ACMG Laboratory Quality Assurance Committee. 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