{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T13:29:24Z","timestamp":1787146164210,"version":"build-2736575974"},"reference-count":43,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp;amp; Rheumatology"],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Mosaicism is a recognized cause of systemic autoinflammatory diseases (SAIDs). Initially described in cryopyrin\u2010associated periodic syndromes (CAPS), it has since been reported in several dominantly inherited SAIDs, including Blau syndrome, tumor necrosis factor receptor\u2013associated periodic syndrome (TRAPS), stimulator of interferon genes\u2013associated vasculopathy with onset in infancy, NLRC4 inflammasomopathies, and familial Mediterranean fever. Recently, somatic variants underlying vacuoles, E1 enzyme, X\u2010linked, autoinflammatory, somatic syndrome (VEXAS syndrome) have extended this to late\u2010onset disease. This study aimed to characterize the prevalence, spectrum, and clinical significance of acquired variants in SAIDs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 5,530 patients referred to a national SAIDs reference center between 2017 and 2025 underwent deep next\u2010generation sequencing autoinflammatory gene panel testing to detect low\u2010level mosaicism. Results underwent multidisciplinary review and correlation with clinical data from electronic medical records.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SAID diagnoses were made in 403 of 5,530 patients (7.3%, 95% confidence interval [CI] 6.6%\u20138.0%). Among these, mosaic variants were identified in 83 patients (20.6%, 95% CI 16.9%\u201324.8%), including patients with VEXAS syndrome (69%), CAPS (24%), TRAPS (5%), Blau syndrome (1%), and NLRC4 inflammasomopathies (1%). Twenty\u2010three distinct mosaic variants were identified across different SAIDs genes; in eight, the minor allele frequency was \u22645%. We report the first case of vertical transmission of TRAPS due to gonosomal mosaicism. AA amyloidosis complicated the disease course in 20% of patients diagnosed with late\u2010onset mosaic CAPS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Somatic mosaicism is a frequent mechanism underlying late\u2010onset SAIDs, which are often diagnosed late and carry a high risk of AA amyloidosis. To our knowledge, this represents the largest genetically heterogeneous single\u2010center cohort of individuals with mosaic SAIDs reported to date.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70282","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:14:46Z","timestamp":1785406486000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Redefining the Landscape: Acquired Mutations Driving Systemic Autoinflammatory Diseases"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3511-6789","authenticated-orcid":false,"given":"Dorota","family":"Rowczenio","sequence":"first","affiliation":[{"name":"National Amyloidosis Centre, Division of Infection, Immunity, and Rare Diseases Royal Free London NHS Foundation Trust  London United 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