ArticleProceedings of the National Academy of Sciences of the United States of America2016
Familial Mediterranean fever mutations lift the obligatory requirement for microtubules in Pyrin inflammasome activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
115 citing papers in PubMed, 1 synthesis or guideline pooled it, 177 citations in OpenAlex.
- Colchicine may become a new cornerstone therapy for coronary artery disease: a meta-analysis of randomized controlled trials.Clinical rheumatology · 2022Pooled it
- Subclinical corneal endothelial alterations in Familial Mediterranean Fever patients during clinical remission.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Article
- KIM-1: A Non-Invasive Marker for Kidney Injury and Treatment Efficacy in FMF.Mediterranean journal of rheumatology · 2026Article
- Monogenic disorders of immunity: Common variants are not so rare.Cell genomics · 2026Review
- Familial Mediterranean Fever: A Comprehensive Review of Pathogenesis, Genetics, and Epigenetic Regulation.Balkan medical journal · 2026Review
- Clinical description, genetic analysis and characterization of two NLRP12 heterozygous VUS variants.Frontiers in immunology · 2026Article
- Innate immune and metabolic signals induce mitochondria-dependent membrane lysis via mitoxyperiosis.Cell · 2025Article
- Hyperimmunoglobulin syndromes: A review of HIGM, HIES, and HIDS.Journal of translational autoimmunity · 2025Review
- RIPK1 autophosphorylation at S161 mediates cell death and inflammation.The Journal of experimental medicine · 2025Article
- Colchicine in coronary artery and cerebrovascular disease: "Old skin for the new ceremony".World journal of cardiology · 2025Review
- Molecular mechanisms and regulation of inflammasome activation and signaling: sensing of pathogens and damage molecular patterns.Cellular & molecular immunology · 2025Review
- Pyrin inflammasome-driven erosive arthritis caused by unprenylated RHO GTPase signaling.EMBO molecular medicine · 2025Article
- The interplay between host immunity andmBio · 2025Review
- The role of epigenetic modifications in systemic autoinflammatory diseases.Current opinion in immunology · 2025Review
- Unresolved Issues in Familial Mediterranean Fever: Is p.R202Q MEFV Variant Potentially Pathogenetic in Unleashing Inflammation?Journal of clinical immunology · 2025Article
- Inflammasome Activation and Neutrophil Extracellular Traps in Atherosclerosis.Journal of atherosclerosis and thrombosis · 2025Review
- Efficacy and Safety of Anakinra in Colchicine-Resistant or -Intolerant Familial Mediterranean Fever: A Single-Center Real-Life Experience.Medicina (Kaunas, Lithuania) · 2025Article
- Enigmatic link between familial mediterranean fever and dietary components: a novel approach to personalized nutrition.BMC nutrition · 2025Article
- The critical role of the ZBP1-NINJ1 axis and IRF1/IRF9 in ethanol-induced cell death, PANoptosis, and alcohol-associated liver disease.bioRxiv : the preprint server for biology · 2025Article
- Familial Mediterranean Fever (FMF): Emerging Concepts in Diagnosis, Pain Management, and Novel Treatment Options: A Narrative Review.Current pain and headache reports · 2025Review
55 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease worldwide. It is caused by mutations in the inflammasome adaptor Pyrin, but how FMF mutations alter signaling in FMF patients is unknown. Herein, we establish Clostridium difficile and its enterotoxin A (TcdA) as Pyrin-activating agents and show that wild-type and FMF Pyrin are differentially controlled by microtubules. Diverse microtubule assembly inhibitors prevented Pyrin-mediated caspase-1 activation and secretion of IL-1β and IL-18 from mouse macrophages and human peripheral blood mononuclear cells (PBMCs). Remarkably, Pyrin inflammasome activation persisted upon microtubule disassembly in PBMCs of FMF patients but not in cells of patients afflicted with other autoinflammatory diseases. We further demonstrate that microtubules control Pyrin activation downstream of Pyrin dephosphorylation and that FMF mutations enable microtubule-independent assembly of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) micrometer-sized perinuclear structures (specks). The discovery that Pyrin mutations remove the obligatory requirement for microtubules in inflammasome activation provides a conceptual framework for understanding FMF and enables immunological screening of FMF mutations.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.