{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T20:42:34Z","timestamp":1793824954957,"version":"4.6.1"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T00:00:00Z","timestamp":1700697600000},"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>Germline <jats:italic>HAVCR2<\/jats:italic> mutation has been reported to be associated with subcutaneous panniculitis-like T-cell lymphoma (SPTCL) leading to Hemophagocytic lymphohistiocytosis (HLH). Several studies have indicated that <jats:italic>HAVCR2<\/jats:italic> mutation can cause HLH even in the absence of lymphoma, though the exact mechanism remains unclear. In this article, we reported five cases of <jats:italic>HAVCR2<\/jats:italic> mutation-associated HLH. Our analysis revealed an elevated level of IL-1RA in the serum of these patients. Furthermore, we investigated the potential mechanisms underlying HLH associated with <jats:italic>HAVCR2<\/jats:italic> mutation based on changes in cytokine levels. Our findings suggest that <jats:italic>HAVCR2<\/jats:italic> mutation may represent a distinct genetic defect underlying HLH, differing from traditional primary HLH.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1271324","type":"journal-article","created":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T10:49:44Z","timestamp":1700736584000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Case Report: HAVCR2 mutation-associated Hemophagocytic lymphohistiocytosis"],"prefix":"10.3389","volume":"14","author":[{"given":"Deli","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingshi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxia","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaofan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21039","article-title":"Hlh-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis","volume":"48","author":"Henter","year":"2007","journal-title":"Pediatr Blood Cancer"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019000936","article-title":"Pediatric hemophagocytic lymphohistiocytosis","volume":"135","author":"Canna","year":"2020","journal-title":"Blood"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/apa.16013","article-title":"Genetics and pathophysiology of haemophagocytic lymphohistiocytosis","volume":"110","author":"Meeths","year":"2021","journal-title":"Acta Paediatrica"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0251-4","article-title":"Germline Havcr2 mutations altering tim-3 characterize subcutaneous panniculitis-like T cell lymphomas with hemophagocytic lymphohistiocytic syndrome","volume":"50","author":"Gayden","year":"2018","journal-title":"Nat Genet"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019003811","article-title":"Havcr2 mutations are associated with severe hemophagocytic syndrome in subcutaneous panniculitis-like T-cell lymphoma","volume":"135","author":"Sonigo","year":"2020","journal-title":"Blood"},{"key":"B6","doi-asserted-by":"publisher","first-page":"391930","DOI":"10.1182\/bloodadvances.2021004562","article-title":"Genetic profiles of subcutaneous panniculitis-like T cell lymphoma and clinicopathological impact of Havcr2 mutations","volume":"5","author":"Koh","year":"2021","journal-title":"Blood Adv"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2023.07.005","article-title":"Good prognosis of adult hemophagocytic lymphohistiocytosis (Hlh) associated with the germline Havcr2 mutation","author":"Boonyabaramee","year":"2023","journal-title":"Exp Hematol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"218692","DOI":"10.1182\/blood-2015-05-644914","article-title":"Multicenter study of combination DEP regimen as a salvage therapy for adult refractory hemophagocytic lymphohistiocytosis","volume":"126","author":"Wang","year":"2015","journal-title":"Blood"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.24188","article-title":"Salvage therapy of refractory hemophagocytic lymphohistiocytosis with alemtuzumab","volume":"60","author":"Marsh","year":"2013","journal-title":"Pediatr Blood Cancer"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30","article-title":"ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2022.282419","article-title":"Germline Havcr2 mutations and their relation to the clinical spectrum of subcutaneous panniculitis-like T-cell lymphoma and hemophagocytic lymphohistiocytosis: results from a multicenter study and meta-analysis","author":"Moonla","year":"2023","journal-title":"Haematologica"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-04-087288","article-title":"Subcutaneous panniculitis-like T-cell lymphoma: definition, classification, and prognostic factors: an eortc cutaneous lymphoma group study of 83 cases","volume":"111","author":"Willemze","year":"2008","journal-title":"Blood"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022007450","article-title":"Treatment of an Hlh-mimic disease based on Havcr2 variants with absent tim-3 expression","volume":"6","author":"Tromp","year":"2022","journal-title":"Blood Adv"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.18817","article-title":"Efficacy of ruxolitinib for havcr2 mutation associated hemophagocytic lymphohistiocytosis and panniculitis manifestations in children","volume":"202","author":"Zhang","year":"2023","journal-title":"Br J Haematology"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.107933","article-title":"Tim-3: an update on immunotherapy","volume":"99","author":"Zhao","year":"2021","journal-title":"Int Immunopharmacol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03626-9","article-title":"Tim-3 restrains anti-tumour immunity by regulating inflammasome activation","volume":"595","author":"Dixon","year":"2021","journal-title":"Nature"},{"key":"B17","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1111\/imm.12812","article-title":"Negative regulation of nod-like receptor protein 3 inflammasome activation by T cell Ig mucin-3 protects against peritonitis","volume":"153","author":"Wang","year":"2018","journal-title":"Immunology"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.222471","article-title":"Ruxolitinib for refractory\/relapsed hemophagocytic lymphohistiocytosis","volume":"105","author":"Wang","year":"2020","journal-title":"Haematologica"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keac440","article-title":"Jak inhibitors in difficult-to-treat adult-onset still\u2019s disease and systemic-onset juvenile idiopathic arthritis","volume":"62","author":"Gillard","year":"2023","journal-title":"Rheumatology"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1271324\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T10:49:48Z","timestamp":1700736588000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1271324\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,23]]},"references-count":19,"alternative-id":["10.3389\/fimmu.2023.1271324"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1271324","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,23]]},"article-number":"1271324"}}