ArticleNature genetics2014
An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome.
Article in Nature genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 378 papers.
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Who cites it
378 citing papers in PubMed, 727 citations in OpenAlex.
- Pathogenic NLRP3 mutants form constitutively active inflammasomes resulting in immune-metabolic limitation of IL-1β production.Nature communications · 2024Trial
- Multisystem inflammation and susceptibility to viral infections in human ZNFX1 deficiency.The Journal of allergy and clinical immunology · 2021Trial
- Advancements in Diagnosis and Care for Immune Dysregulation and Inborn Errors of Immunity in Pediatric Rheumatology: Our 50-Year Journey.Arthritis care & research · 2026Review
- Innate immune sensors of inflammasomes and PANoptosomes: structural-mechanistic insights and therapeutic implications.Cell research · 2026Review
- Interface between inborn errors of immunity and rheumatological disorders in children: A pediatrician's conundrum.World journal of clinical pediatrics · 2026Review
- Beyond NLRP3: expanding the spectrum of NLR-associated autoinflammatory diseases.Rheumatology (Oxford, England) · 2026Article
- Complexities in the Diagnostic Evaluation and Treatment of Infant Hemophagocytic Lymphohistiocytosis.Hematology reports · 2026Article
- Autosomal recessive A20 zinc finger 7 mutation is associated with early-onset lupus-like disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- The NLRP3 inflammasome as a dynamic context-dependent regulator: mechanisms, disease progression, and therapeutic implications.Journal of translational medicine · 2026Review
- Decoding variants of uncertain significance in systemic autoinflammatory diseases.Nature reviews. Rheumatology · 2026Review
- Free IL-18 in NLRC4-associated autoinflammatory disease without macrophage activation syndrome.Rheumatology (Oxford, England) · 2026Article
- A neurologist's guide to VEXAS syndrome: Differentiating somatic autoinflammation from autoimmune mimics.Intractable & rare diseases research · 2026Review
- TRIM21 facilitates inflammasome assembly and contributes to autoinflammatory disease.Nature communications · 2026Article
- Chimeric antigen receptor T-cell therapies related to immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome: Diagnosis, high-risk factors, and management.Chinese medical journal · 2026Review
- Current understanding of the NLRC4 Inflammasome in autoinflammation and enterocolitis.Communications biology · 2026Review
- The Roles of Interleukin-18 in Inflammation and Autoimmune Disease.Clinical reviews in allergy & immunology · 2026Review
- Serum Cytokine Profiling Differentiates Underlying Diseases in Cytokine Storm Syndrome.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Article
- Advances in the research of gasdermin-dependent pyroptosis mechanisms and therapeutic targets in inflammatory diseases.Apoptosis : an international journal on programmed cell death · 2026Review
- Autoinflammation with infantile enterocolitis associated with a novel CARD domain mutation inFrontiers in pediatrics · 2026Article
318 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 9 institutions in 2 countries.
Funding
Abstract
Inflammasomes are innate immune sensors that respond to pathogen- and damage-associated signals with caspase-1 activation, interleukin (IL)-1β and IL-18 secretion, and macrophage pyroptosis. The discovery that dominant gain-of-function mutations in NLRP3 cause the cryopyrin-associated periodic syndromes (CAPS) and trigger spontaneous inflammasome activation and IL-1β oversecretion led to successful treatment with IL-1-blocking agents. Herein we report a de novo missense mutation (c.1009A > T, encoding p.Thr337Ser) affecting the nucleotide-binding domain of the inflammasome component NLRC4 that causes early-onset recurrent fever flares and macrophage activation syndrome (MAS). Functional analyses demonstrated spontaneous inflammasome formation and production of the inflammasome-dependent cytokines IL-1β and IL-18, with the latter exceeding the levels seen in CAPS. The NLRC4 mutation caused constitutive caspase-1 cleavage in cells transduced with mutant NLRC4 and increased production of IL-18 in both patient-derived and mutant NLRC4-transduced macrophages. Thus, we describe a new monoallelic inflammasome defect that expands the monogenic autoinflammatory disease spectrum to include MAS and suggests new targets for therapy.
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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.