Autoinflammatory & rare systemic diseases
Rare and Novel RELA Variants Contribute to Systemic Autoimmunity
Authors' conclusion
We expand upon the clinical syndromes linked to RELA dysfunction and uncover rare/novel variants that have distinct functional effects on gene transcription downstream of NF-κB and IFNβ promoter elements.
Study context
- Population
- Patients with autoimmune diseases carrying novel/rare RELA variantsseven novel/rare RELA variants
- Comparison
- Mutant RELA variants vs wild-type RELA
Methodological detailswhole-exome sequencing, functional assays in HEK293 cells and patient peripheral blood mononuclear cells (PBMCs)
- Whole-exome sequencing
- Functional assays in HEK293 cells and patient PBMCs
Main finding
As reported in the abstract
- RELAI250V, RELAR295H and RELAE3* displayed a loss in NF-κB transcriptional activity
- RELAI250V and RELAR295H induced hyperactivation of the IFNβ promoter
- Ectopically expressed RELAI250V protein levels reduced vs RELAWT
- No elevated IFN gene signature in patient PBMCs after toll-like receptor (TLR) activation overall
- Patient heterozygous for I250V had elevated IFNβ transcripts after TLR7/8 activation
Original publication
Rare and Novel RELA Variants Contribute to Systemic Autoimmunity. Arthritis Rheumatol. Published 26 December 2025. doi:10.
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