Trial reportThe Journal of clinical investigation2018
Loss-of-function CARD8 mutation causes NLRP3 inflammasome activation and Crohn's disease.
Trial report in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.
What it found
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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
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- mRNA expression of NLRP3 and IL1B in inflammatory bowel diseases: a systematic review and meta-analysis.BMC gastroenterology · 2025Pooled it
- [Regulatory mechanisms of post-translational modifications in inflammasome signaling: a review].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Review
- The NLRP3 Inflammasome: Mechanisms of Activation, Regulation, and Therapeutic Opportunities.MedComm · 2026Review
- A single-cell atlas of ulcerative colitis reveals neutrophil-stromal circuits linked to biologic therapy resistance.Frontiers in immunology · 2026Article
- Macrophage pyroptosis in inflammatory bowel disease: mechanistic insights, pathological roles and treatment strategies.Frontiers in immunology · 2026Review
- NLRP3 Inflammasome as Potential Predictor of Non-Responsiveness to Immunosuppressive Treatment in Lupus Nephritis.International journal of molecular sciences · 2025Article
- Role of NLRP3 Inflammasomes in Disorders of Children's Digestive Systems: A Narrative Review.Pediatric reports · 2025Review
- Peroxiredoxin 1 promotes intestinal inflammation by activating the NLRP3 inflammasome in macrophages through lysosomal disruption in Crohn's disease.Cell death & disease · 2025Article
- The Multifaceted Role of Macrophages in Biology and Diseases.International journal of molecular sciences · 2025Review
- Molecular mechanisms of emerging inflammasome complexes and their activation and signaling in inflammation and pyroptosis.Immunological reviews · 2025Review
- LRRK2-mediated NLRC4 phosphorylation differentially regulates IL-1β/IL-18 secretion.Frontiers in immunology · 2025Article
- Genome sequencing provides novel insights into diadromous migration adaptations in the roughskin sculpin,ZooKeys · 2025Article
- Review
- The Multiple Roles of Heat Shock Proteins in the Development of Inflammatory Bowel Disease.Current molecular medicine · 2025Review
- Mechanism of cell death and its application in the repair of inflammatory bowel disease by mesenchymal stem cells.Frontiers in immunology · 2025Review
- Inflammasome components as new therapeutic targets in inflammatory disease.Nature reviews. Immunology · 2025Review
- CARD8 polymorphisms among bacterial meningitis patients in North-West Ethiopia.BMC infectious diseases · 2024Article
- NLRP3 Negative Regulation Mechanisms in the Resting State and Its Implications for Therapeutic Development.International journal of molecular sciences · 2024Review
- CARD8: A Novel Inflammasome Sensor with Well-Known Anti-Inflammatory and Anti-Apoptotic Activity.Cells · 2024Review
- NLRP inflammasomes in health and disease.Molecular biomedicine · 2024Review
10 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
12 authors at 2 institutions in 1 country.
Funding
Abstract
In these studies, we evaluated the contribution of the NLRP3 inflammasome to Crohn's disease (CD) in a kindred containing individuals having a missense mutation in CARD8, a protein known to inhibit this inflammasome. Whole exome sequencing and PCR studies identified the affected individuals as having a V44I mutation in a single allele of the T60 isoform of CARD8. The serum levels of IL-1β in the affected individuals were increased compared with those in healthy controls, and their peripheral monocytes produced increased amounts of IL-1β when stimulated by NLRP3 activators. Immunoblot studies probing the basis of these findings showed that mutated T60 CARD8 failed to downregulate the NLRP3 inflammasome because it did not bind to NLRP3 and inhibit its oligomerization. In addition, these studies showed that mutated T60 CARD8 exerted a dominant-negative effect by its capacity to bind to and form oligomers with unmutated T60 or T48 CARD8 that impeded their binding to NLRP3. Finally, inflammasome activation studies revealed that intact but not mutated CARD8 prevented NLRP3 deubiquitination and serine dephosphorylation. CD due to a CARD8 mutation was not effectively treated by anti-TNF-α, but did respond to IL-1β inhibitors. Thus, patients with anti-TNF-α-resistant CD may respond to this treatment option.
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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.