ArticleEMBO molecular medicine2019
Pyrin dephosphorylation is sufficient to trigger inflammasome activation in familial Mediterranean fever patients.
Article in EMBO molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 63 citations in OpenAlex.
- Innate immune sensors of inflammasomes and PANoptosomes: structural-mechanistic insights and therapeutic implications.Cell research · 2026Review
- Decoding variants of uncertain significance in systemic autoinflammatory diseases.Nature reviews. Rheumatology · 2026Review
- ThebioRxiv : the preprint server for biology · 2026Article
- The Relationship Between Gene Subtypes, Symptoms, and Cardiac Function in Patients with Familial Mediterranean Fever.Journal of clinical medicine · 2026Article
- Familial Mediterranean Fever: A Comprehensive Review of Pathogenesis, Genetics, and Epigenetic Regulation.Balkan medical journal · 2026Review
- Pyrin inflammasome-driven erosive arthritis caused by unprenylated RHO GTPase signaling.EMBO molecular medicine · 2025Article
- Unresolved Issues in Familial Mediterranean Fever: Is p.R202Q MEFV Variant Potentially Pathogenetic in Unleashing Inflammation?Journal of clinical immunology · 2025Article
- Review
- GSDMD-mediated pyroptosis: molecular mechanisms, diseases and therapeutic targets.Molecular biomedicine · 2025Review
- Sequential immunotherapy: towards cures for autoimmunity.Nature reviews. Drug discovery · 2024Review
- Pyrin Inflammasome Activation Defines Colchicine-Responsive SURF Patients from FMF and Other Recurrent Fevers.Journal of clinical immunology · 2024Article
- Article
- Cellular models in autoinflammatory disease research.Clinical & translational immunology · 2024Review
- Recent Insights in Pyrin Inflammasome Activation: Identifying Potential Novel Therapeutic Approaches in Pyrin-Associated Autoinflammatory Syndromes.Journal of clinical immunology · 2023Review
- Article
- Mutations in the B30.2 and the central helical scaffold domains of pyrin differentially affect inflammasome activation.Cell death & disease · 2023Article
- The role of pyroptosis in inflammatory diseases.Frontiers in cell and developmental biology · 2023Review
- The pyrin inflammasome, a leading actor in pediatric autoinflammatory diseases.Frontiers in immunology · 2023Review
- Molecular Mechanisms of Pyroptosis.Methods in molecular biology (Clifton, N.J.) · 2023Review
- Transcriptional licensing is required for Pyrin inflammasome activation in human macrophages and bypassed by mutations causing familial Mediterranean fever.PLoS biology · 2022Article
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Authors and funding
18 authors at 5 institutions in 1 country.
Funding
Abstract
Familial Mediterranean fever (FMF) is the most frequent hereditary systemic autoinflammatory syndrome. FMF is usually caused by biallelic mutations in the MEFV gene, encoding Pyrin. Conclusive genetic evidence lacks for about 30% of patients diagnosed with clinical FMF. Pyrin is an inflammasome sensor maintained inactive by two kinases (PKN1/2). The consequences of MEFV mutations on inflammasome activation are still poorly understood. Here, we demonstrate that PKC superfamily inhibitors trigger inflammasome activation in monocytes from FMF patients while they trigger a delayed apoptosis in monocytes from healthy donors. The expression of the pathogenic p.M694V MEFV allele is necessary and sufficient for PKC inhibitors (or mutations precluding Pyrin phosphorylation) to trigger caspase-1- and gasdermin D-mediated pyroptosis. In line with colchicine efficacy in patients, colchicine fully blocks this response in FMF patients' monocytes. These results indicate that Pyrin inflammasome activation is solely controlled by Pyrin (de)phosphorylation in FMF patients while a second control mechanism restricts its activation in healthy donors/non-FMF patients. This study paves the way toward a functional characterization of MEFV variants and a functional test to diagnose FMF.
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