Name: Autoinflammation with episodic fever and lymphadenopathy | Acronym: AIEFL
Alt. names: RIPK1 AD-GOF

Gene: RIPK1 | MOI: Autosomal dominant | Mechanism of action: Gain of Function

No. of cases in DB: 0 | First reported in: 2020

Last updated on: 2024-07-24 22:42:37 by Xiao P. Peng

OMIM: 618852

Orphanet: -

MONDO: -

DOID: -

ClinGen:

Heterozygous missense GOF mutations affecting the same residue (D324N/H/Y) impair caspase-8-dependent RIPK1 cleavage and inactivation, leading to AD CRIA (cleavage-resistant RIPK1-induced autoinflammatory) syndrome [OMIM: 618852], characterized by early-onset periodic fevers (every one to few weeks, lasting several days) with accompanying lymphadenopathy and variable hepatosplenomegaly (PMID: 31827281, 31827280). Labs show increased serum levels of pro-inflammatory cytokines including TNF-α, IL-6, IL-8, IL-1β, and IL-10. Tao et al. (2020) showed that these activating RIPK1 variants render patient PBMCs hypersensitive to TNF-induced cell death by apoptosis, necroptosis and ferroptosis, while their fibroblasts actually downregulate RIPK1 expression and show increased resistance to the same cell death pathways.

CRIA patients have been reported to respond to treatment with IL-6 blockade rather than TNF inhibition