{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T23:43:03Z","timestamp":1792539783412,"version":"4.5.0"},"reference-count":15,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"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><jats:title>Background<\/jats:title><jats:p>UNC93B1 is a transmembrane protein essential for regulating toll-like receptors (TLRs). Pathogenic variants in human <jats:italic>UNC93B1<\/jats:italic> have recently been described in a limited number of patients with childhood systemic lupus erythematosus and chilblain lupus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Demographic data, medical history, and physical examination findings were obtained. Whole-exome sequencing and Sanger sequencing were performed. The interferon-stimulated gene (ISG) score was analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We report four patients with a novel <jats:italic>UNC93B1<\/jats:italic> c.1007G&amp;gt;A p.R336H variant, including three presenting with juvenile arthritis or rheumatoid arthritis, and one with a predominant phenotype of ITP. In addition to arthritis, these patients presented with interstitial pneumonia as the dominant feature. ISG expression analysis during active disease revealed overexpression of IFN-stimulated cytokine genes and an elevated ISG score in P4. To date, 25 cases with <jats:italic>UNC93B1<\/jats:italic> pathogenic mutations have been reported, including 13 with childhood-onset systemic lupus erythematosus (SLE) and 12 with cutaneous lupus. Management of these patients has varied based on clinical manifestations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>UNC93B1-<\/jats:italic>mutation<jats:italic>-<\/jats:italic>associated disease should be considered in the context of early-onset autoimmune disease, especially childhood-onset SLE, juvenile arthritis, and rheumatoid arthritis. Pulmonary involvement should also be monitored in these patients.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1671984","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T05:50:22Z","timestamp":1759297822000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Case Report: Novel UNC93B1 variant causes rheumatoid arthritis and interstitial pneumonia"],"prefix":"10.3389","volume":"16","author":[{"given":"Tingyan","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbin","family":"Ou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adi9575","article-title":"Disrupted 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and treatment of monogenic systemic vasculitis","volume":"21","author":"Gul","year":"2025","journal-title":"Nat Rev Rheumatol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.10.031","article-title":"Disease-associated mutations identify a novel region in human STING necessary for the control of type I interferon signaling","volume":"140","author":"Melki","year":"2017","journal-title":"J Allergy Clin Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.27860","article-title":"UNC93B1 attenuates the cGAS-STING signaling pathway by targeting STING for autophagy-lysosome degradation","volume":"94","author":"Zhu","year":"2022","journal-title":"J Med Virol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202048901","article-title":"UNC93B1 curbs cytosolic DNA signaling by promoting STING degradation","volume":"51","author":"He","year":"2021","journal-title":"Eur J Immunol"}],"container-title":["Frontiers in 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