Autoinflammatory & rare systemic diseases
A Rare RIPK3 Variant Enhances Necroptosis and Promotes Inflammation in a Still Disease–Like Autoinflammatory Syndrome
Authors' conclusion
This study describes a familial Still disease-like autoinflammatory syndrome caused by a gain-of-function RIPK3 variant. Our findings establish aberrant RIPK3 activation as a driver of autoinflammation and expand the spectrum of human RIPK3-associated diseases.
Study context
- Population
- A three-generation family with three individuals affected by a Still disease-like autoinflammatory syndromethree affected individuals
Methodological detailswhole-exome sequencing, functional analyses, transcriptomic profiling
- Whole-exome sequencing
- Functional analyses
- Transcriptomic profiling
Main finding
As reported in the abstract
- Heterozygous RIPK3 p.Q134K variant identified in all affected individuals
- Gain-of-function activity: enhanced RIPK3 kinase activity and increased RIPK3 self-association, promoting mixed-lineage kinase domain-like protein phosphorylation and necroptosis
- RNA sequencing of PBMCs (one patient): marked up-regulation of NF-κB and MAPK signalling and elevated IL-6 and TNF-α expression, suppressed by pharmacologic RIPK3 inhibition
Original publication
A Rare RIPK3 Variant Enhances Necroptosis and Promotes Inflammation in a Still Disease–Like Autoinflammatory Syndrome. Arthritis Rheumatol. Published 3 May 2026. doi:10.
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