Autoinflammatory & rare systemic diseases
Redefining the Landscape: Acquired Mutations Driving Systemic Autoinflammatory Diseases
Authors' conclusion
Somatic mosaicism is a frequent mechanism underlying late-onset SAIDs, which are often diagnosed late and carry a high risk of AA amyloidosis.
Study context
- Population
- Patients referred to a national systemic autoinflammatory diseases (SAIDs) reference center between 2017 and 2025 tested with a deep NGS autoinflammatory gene panel
- Participants
- 5,530 patients
- Outcome
- Prevalence, spectrum and clinical significance of acquired (mosaic) variants in SAIDs
Methodological detailssingle-centre, national reference centre, deep next-generation sequencing gene panel, Results underwent multidisciplinary review and correlation with clinical data from electronic medical records
- Single-centre
- National reference centre
- Deep next-generation sequencing gene panel
- Results underwent multidisciplinary review and correlation with clinical data from electronic medical records
Main finding
As reported in the abstract
Mosaic variants among patients with SAID diagnosis
- SAID diagnoses made
- 403 of 5,530 (7.3%, 95% CI 6.6%-8.0%)
- Mosaic variants among SAID diagnoses
- 83 (20.6%, 95% CI 16.9%-24.8%)
- Spectrum of mosaic cases: VEXAS syndrome
- 69%
- Spectrum of mosaic cases: Cryopyrin-associated periodic syndromes (CAPS)
- 24%
- Spectrum of mosaic cases: TRAPS
- 5%
- Spectrum of mosaic cases: Blau syndrome
- 1%
- Spectrum of mosaic cases: NLRC4 inflammasomopathies
- 1%
- Distinct mosaic variants
- 23
- Variants with minor allele frequency ≤5%
- 8
Observational data: associations, not effects.
Further findings
AA amyloidosis in late-onset mosaic CAPS
- AA amyloidosis complicated disease course
- 20%
Vertical transmission of TRAPS due to gonosomal mosaicism
- First reported case
Original publication
Redefining the Landscape: Acquired Mutations Driving Systemic Autoinflammatory Diseases. Arthritis Rheumatol. Published 30 July 2026. doi:10.
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