Autoinflammatory & rare systemic diseases
A germline IκBα mutation outside the signal reception domain blocks nuclear translocation of NFκB1 and associates with autoinflammation-like features
Authors' conclusion
NFKBIA variants not localising to the signal reception domain can affect IκBα function and consequently restrict the canonical activation of NFκB.
Study context
- Population
- A family with a history of arthritis and psoriasis harbouring the p.Gln228* variant in NFKBIA
- Outcome
- Functional effects of the NFKBIA p.Gln228* variant
Methodological detailswhole-exome sequencing, family study
- Whole-exome sequencing
- Family study
Main finding
As reported in the abstract
- Did not affect induced degradation of IκBα
- Truncating effect and reduced NFκB activation on expression in HEK293T cells
- Substantially reduced nuclear levels of NFκB1 p50 in patients' PBMCs, suggesting functional insufficiency of NFκB1
- High serum IL-18 and enhanced induced ASC speck formation and IL-1β secretion in vitro, suggesting enhanced inflammasome activation
Original publication
A germline IκBα mutation outside the signal reception domain blocks nuclear translocation of NFκB1 and associates with autoinflammation-like features. Ann Rheum Dis. Published 5 September 2025. doi:10.
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