This single-centre cohort study evaluated the prevalence, spectrum, and clinical impact of acquired (somatic mosaic) variants in systemic autoinflammatory diseases (SAIDs) among 5,530 patients referred between 2017–2025, using deep next-generation sequencing of an autoinflammatory gene panel.
SAIDs were diagnosed in 403/5,530 patients (7.3%); mosaic variants accounted for 20.6% of SAIDs diagnoses (83/403). VEXAS made up 69% of mosaic cases, CAPS 24%, TRAPS 5%, Blau syndrome 1%, and NLRC4 inflammasomopathies 1%. Eight variants had a minor allele frequency ≤5%, and AA amyloidosis complicated 20% of late-onset mosaic CAPS cases.
Single-centre design limits generalisability. Referral bias likely enriches for complex or late-onset cases. Clinical correlation relied on electronic medical records, which may be incomplete.
Use deep next-generation sequencing panels capable of detecting low-level mosaicism (≤5% allele frequency) when evaluating adults with late-onset SAIDs — standard sequencing will miss these. Screen mosaic CAPS patients closely for AA amyloidosis, which occurred in 1 in 5 late-onset cases.
