{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T11:10:02Z","timestamp":1768216202238,"version":"3.49.0"},"reference-count":9,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Blau syndrome is a rare autoinflammatory disorder caused by gain-of-function mutations in the NOD2 (nucleotide binding oligomerization domain containing 2 receptor) gene. Blau Syndrome presents with the diagnostic triad of chronic polyarticular synovitis, recurrent uveitis, and dermatitis. Notably, patients often develop systemic granulomatous inflammation affecting multiple organs, particularly the kidney and liver. Here we report a case of Blau syndrome presented with early-onset arthritis, uveitis, and renal involvement, evidenced by granulomas tubulointerstitial nephritis. Genetic testing showed a pathogenic p.R334W NOD2 mutation demonstrating constitutive NF-\u03baB activation and excessive proinflammatory cytokine production. While initial corticosteroid therapy improved articular and ocular symptoms, renal dysfunction persisted until baricitinib (4 mg\/day) initiation, which rapidly normalized renal function and permitted steroid tapering. Granulomatous inflammation in Blau syndrome is mediated by IFN-\u03b3 and sustained JAK-STAT activation, making JAK1\/2 inhibition a rational therapeutic target. Although TNF-\u03b1 inhibitors show efficacy in some cases, our experience supports baricitinib\u2019s potential for refractory disease, particularly with renal involvement. Baricitinib can offer distinct advantages over biologics and effectively downregulates inflammation in Blau syndrome.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1665949","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T08:13:58Z","timestamp":1768205638000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Potential benefits of JAK inhibitor therapy in Blau syndrome: a case report"],"prefix":"10.3389","volume":"16","author":[{"given":"Yu","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-juan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuoli","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00431-023-05204-9","article-title":"Management of Blau syndrome: review and proposal of a treatment algorithm","volume":"183","author":"Lassoued Ferjani","year":"2024","journal-title":"Eur J Pediatr"},{"key":"B2","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1016\/S0140-6736(23)00550-0","article-title":"Imaging inflammation in early-onset sarcoidosis: granulomatous anterior uveitis in a 7-year-old girl","volume":"401","year":"2023","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"crossref","DOI":"10.3109\/08820538.2013.825285","article-title":"Blau syndrome-associated uveitis and the NOD2 gene","volume":"28","author":"Pillai","year":"2013","journal-title":"Semin Ophthalmol"},{"key":"B4","doi-asserted-by":"crossref","DOI":"10.1016\/j.ophtha.2022.03.014","article-title":"Genetic and clinical features of blau syndrome among chinese patients with uveitis","volume":"129","author":"Zhong","year":"2022","journal-title":"Ophthalmology"},{"key":"B5","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.autrev.2012.07.028","article-title":"Blau syndrome, clinical and genetic aspects","volume":"12","author":"Sfriso","year":"2012","journal-title":"Autoimmun Rev"},{"key":"B6","doi-asserted-by":"crossref","first-page":"895765","DOI":"10.3389\/fimmu.2022.895765","article-title":"Potential benefits of TNF targeting therapy in blau syndrome, a NOD2-associated systemic autoinflammatory granulomatosis","volume":"13","author":"Matsuda","year":"2022","journal-title":"Front Immunol"},{"key":"B7","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1186\/s12969-021-00634-x","article-title":"Tofacitinib effectiveness in Blau syndrome: a case series of Chinese paediatric patients","volume":"19","author":"Zhang","year":"2021","journal-title":"Pediatr Rheumatol Online J"},{"key":"B8","doi-asserted-by":"crossref","first-page":"1759720X221093211","DOI":"10.1177\/1759720X221093211","article-title":"Clinical and immunological study of tofacitinib and baricitinib in refractory blau syndrome: Case report and literature review","volume":"14","author":"\u00c1lvarez-Reguera","year":"2022","journal-title":"Ther Adv Musculoskelet Dis"},{"key":"B9","doi-asserted-by":"crossref","first-page":"101378","DOI":"10.1016\/j.trim.2021.101378","article-title":"First report of liver transplantation in Blau syndrome: The challenges faced in this rare granulomatous liver disease","volume":"65","author":"Sinharay","year":"2021","journal-title":"Transpl Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1665949\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T08:14:00Z","timestamp":1768205640000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1665949\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,12]]},"references-count":9,"alternative-id":["10.3389\/fimmu.2025.1665949"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1665949","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,12]]},"article-number":"1665949"}}