A Rare RIPK3 Variant Enhances Necroptosis and Promotes Inflammation in a Still's Disease-like Autoinflammatory Syndrome - PubMed
3 hours ago
- #autoinflammatory syndrome
- #RIPK3
- #necroptosis
- A rare RIPK3 p.Q134K variant was identified in a three-generation family with Still's Disease-like autoinflammatory syndrome.
- The RIPK3 p.Q134K variant exhibits gain-of-function activity, enhancing kinase activity, RIPK3 self-association, and promoting MLKL phosphorylation and necroptosis.
- Transcriptomic profiling showed upregulation of NF-κB and MAPK signaling pathways, along with elevated IL-6 and TNF-α expression in affected individuals.
- Pharmacological inhibition of RIPK3 effectively suppressed inflammatory responses, suggesting a potential therapeutic target.
- This study establishes aberrant RIPK3 activation as a driver of autoinflammation, expanding the spectrum of RIPK3-associated diseases.