{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:08:47Z","timestamp":1770163727027,"version":"3.49.0"},"reference-count":12,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly recognized adult-onset autoinflammatory disorder caused by somatic mutations in the UBA1 gene. It typically presents in older males with systemic inflammation, hematologic abnormalities, and a relapsing, treatment-refractory course. Reports in younger patients remain rare, and pulmonary involvement is often misdiagnosed as infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>We present a 30-year-old man with a two-year history of recurrent scleritis, fever, cough, auricular chondritis, rash, and transfusion-dependent macrocytic anemia. Despite multiple immunosuppressants and broad-spectrum antimicrobials, symptoms persisted. Imaging revealed relapsing bilateral ground-glass pulmonary infiltrates, and repeated microbiologic studies were negative. Bone marrow showed vacuolated precursors and cytogenetic abnormalities. A somatic UBA1 mutation (NM_003334 exon3 c.121A&amp;gt;G p.M41V) was detected with high variant allele frequency in blood and marrow, and notably, also in bronchoalveolar lavage cells. The patient was diagnosed with VEXAS syndrome with early myelodysplastic features. Tocilizumab induced transient improvement, but disease relapse followed. He is currently being evaluated for allogeneic hematopoietic stem cell transplantation (AHSCT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This case represents one of the youngest patients reported with VEXAS syndrome and provides rare evidence of UBA1 mutation in pulmonary cells, supporting the concept of tissue-level clonal inflammation. It highlights the importance of considering VEXAS in younger patients with unexplained systemic inflammation, cytopenias, and non-infectious pulmonary infiltrates, and supports early genetic testing and multidisciplinary management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1737665","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T11:09:13Z","timestamp":1770116953000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Early-onset VEXAS syndrome with recurrent pulmonary inflammation and myelodysplasia: a diagnostic and therapeutic challenge"],"prefix":"10.3389","volume":"17","author":[{"given":"Xianghong","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianyong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaping","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayuan","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2026834","article-title":"Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease","volume":"383","author":"Beck","year":"2020","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1097\/BOR.0000000000001068","article-title":"VEXAS syndrome: an adult-onset autoinflammatory disorder with underlying somatic mutation","volume":"37","author":"Kotter","year":"2025","journal-title":"Curr Opin Rheumatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-023-05513-0","article-title":"Clinical characteristics, disease trajectories and management of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome: a systematic review","volume":"44","author":"Kouranloo","year":"2024","journal-title":"Rheumatol Int"},{"key":"B4","doi-asserted-by":"crossref","DOI":"10.1007\/s00277-024-05750-8","article-title":"Could it be VEXAS","volume":"103","author":"Guerineau","year":"2024","journal-title":"Ann Hematol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kead697","article-title":"Treatment experiences with focus on IL-6R inhibition in patients with VEXAS syndrome and a case of remission with azacytidine treatment","volume":"64","author":"Johansen","year":"2025","journal-title":"Rheumatol (Oxford)"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-025-06207-2","article-title":"VEXAS syndrome: is it more a matter of inflammation or hematopoietic clonality? A case series approach to diagnosis, therapeutic strategies and transplant management","volume":"104","author":"Costa","year":"2025","journal-title":"Ann Hematol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.19979","article-title":"JAK2 is a critical therapeutic target in VEXAS syndrome treated with ruxolitinib","volume":"206","author":"Ceccardi","year":"2025","journal-title":"Br J Haematol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-220876","article-title":"Tocilizumab in VEXAS relapsing polychondritis: a single-center pilot study in Japan","volume":"80","author":"Kirino","year":"2021","journal-title":"Ann Rheum Dis"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.17893","article-title":"Azacitidine for patients with Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome (VEXAS) and myelodysplastic syndrome: data from the French VEXAS registry","volume":"196","author":"Comont","year":"2022","journal-title":"Br J Haematol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1182\/bloodadvances.2021004749","article-title":"Successful allogeneic hematopoietic stem cell transplantation in patients with VEXAS syndrome: a 2-center experience","volume":"6","author":"Diarra","year":"2022","journal-title":"Blood Adv"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-022-01698-8","article-title":"A Phase II prospective trial of azacitidine in steroid-dependent or refractory systemic autoimmune\/inflammatory disorders and VEXAS syndrome associated with MDS and CMML","volume":"36","author":"Mekinian","year":"2022","journal-title":"Leukemia"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2023023723","article-title":"Molecular and clinical presentation of UBA1-mutated myelodysplastic syndromes","volume":"144","author":"Sirenko","year":"2024","journal-title":"Blood"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1737665\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T11:09:16Z","timestamp":1770116956000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1737665\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,3]]},"references-count":12,"alternative-id":["10.3389\/fimmu.2026.1737665"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1737665","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,3]]},"article-number":"1737665"}}