Autoinflammatory & rare systemic diseases
Pyrin variant E148Q potentiates inflammasome activation and the effect of pathogenic mutations in cis
Authors' conclusion
The p.E148Q variant in pyrin potentiates inflammasome activation in vitro. In cis, this effect is additive to known pathogenic FMF mutations.
Study context
- Population
- Individuals with autoinflammatory diseases in the Australian Autoinflammatory Disease RegistrY (AADRY); HEK293T and THP-1 cell linesTwo FMF families
- Comparison
- Pyrin variant combinations including p.E148Q, alone and in cis to classical FMF mutations
- Outcome
- Ability of pyrin to form an active inflammasome complex in cell lines
Methodological detailsregistry interrogation (AADRY), in vitro functional validation, HEK293T ASC cells, flow cytometry, THP-1 cells, ELISA
- Registry interrogation (AADRY)
- In vitro functional validation
- HEK293T ASC cells, flow cytometry
- THP-1 cells, ELISA
Main finding
As reported in the abstract
- p.E148Q pyrin spontaneously potentiated inflammasome formation, with increased IL-1β and IL-18 secretion
- p.E148Q in cis to classical FMF mutations provided significant potentiation of inflammasome formation
Further findings
Inheritance in AADRY
- p.E148Q allele observed in individuals with autoinflammatory diseases alone or with other pyrin variants
- Two FMF families harboured p.E148Q-M694I in cis with dominant heritability
Original publication
Pyrin variant E148Q potentiates inflammasome activation and the effect of pathogenic mutations in cis. Rheumatology (Oxford). Published 22 July 2023. doi:10.
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