ArticleThe Journal of experimental medicine2017
Autoinflammatory periodic fever, immunodeficiency, and thrombocytopenia (PFIT) caused by mutation in actin-regulatory gene WDR1.
Article in The Journal of experimental medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 141 citations in OpenAlex.
- Autosomal dominant gain-of-function mutations in LCP1 cause a syndromic neutropenia and immunodeficiency.Genes & diseases · 2027Article
- Advances in targeting IL-1 family cytokines for the treatment of inflammatory diseases.Nature reviews. Rheumatology · 2026Review
- Evolutionarily conserved short linear motifs drive actin filament binding.Nature cell biology · 2026Article
- Shared Genetics of Kidney Function Traits and Bladder Cancer: A Genome-Wide Cross-Trait Analysis.Cancer medicine · 2026Article
- Immune-related actinopathies at the cross-road of immunodeficiency, autoimmunity and autoinflammation.Nature reviews. Immunology · 2026Review
- IL-1 family cytokines in inflammation and immunity.Cellular & molecular immunology · 2025Review
- LIMK1 variants are associated with divergent endocrinological phenotypes and altered exocytosis dynamics.iScience · 2025Article
- How (Ultra-)Rare Gene Variants Improve Our Understanding of More Common Autoimmune and Inflammatory Diseases.ACR open rheumatology · 2025Review
- INTEGRIN FUNCTION IN LEUKOCYTE-MEDIATED INFLAMMATION-ACTINOPATHIES IN IMMUNE DISEASES.Transactions of the American Clinical and Climatological Association · 2025Review
- Methods for Modeling Early Life Stress in Rodents.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Inflammatory turmoil within: an exploration of autoinflammatory disease genetic underpinnings, clinical presentations, and therapeutic approaches.Advances in rheumatology (London, England) · 2024Review
- Interleukin‑18 binding protein: Biological properties and roles in human and animal immune regulation (Review).Biomedical reports · 2024Review
- Interrupting an IFN-γ-dependent feedback loop in the syndrome of pyogenic arthritis with pyoderma gangrenosum and acne.Annals of the rheumatic diseases · 2024Article
- Association of neutrophil defects with oral ulcers but undetermined role of neutrophils in recurrent aphthous stomatitis.Heliyon · 2024Review
- Cellular models in autoinflammatory disease research.Clinical & translational immunology · 2024Review
- The α-arrestin SUP-13/ARRD-15 promotes isoform turnover of actin-interacting protein 1 inPNAS nexus · 2023Article
- The pyrin inflammasome, a leading actor in pediatric autoinflammatory diseases.Frontiers in immunology · 2023Review
- Plasma proteomic profiling in postural orthostatic tachycardia syndrome (POTS) reveals new disease pathways.Scientific reports · 2022Article
- Pathophysiology, clinical manifestations and current management of IL-1 mediated monogenic systemic autoinflammatory diseases, a literature review.Pediatric rheumatology online journal · 2022Review
- Paediatric Behçet's Disease: A Comprehensive Review with an Emphasis on Monogenic Mimics.Journal of clinical medicine · 2022Review
9 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 3 institutions in 1 country.
Funding
Abstract
The importance of actin dynamics in the activation of the inflammasome is becoming increasingly apparent. IL-1β, which is activated by the inflammasome, is known to be central to the pathogenesis of many monogenic autoinflammatory diseases. However, evidence from an autoinflammatory murine model indicates that IL-18, the other cytokine triggered by inflammasome activity, is important in its own right. In this model, autoinflammation was caused by mutation in the actin regulatory gene WDR1 We report a homozygous missense mutation in WDR1 in two siblings causing periodic fevers with immunodeficiency and thrombocytopenia. We found impaired actin dynamics in patient immune cells. Patients had high serum levels of IL-18, without a corresponding increase in IL-18-binding protein or IL-1β, and their cells also secreted more IL-18 but not IL-1β in culture. We found increased caspase-1 cleavage within patient monocytes indicative of increased inflammasome activity. We transfected HEK293T cells with pyrin and wild-type and mutated WDR1 Mutant protein formed aggregates that appeared to accumulate pyrin; this could potentially precipitate inflammasome assembly. We have extended the findings from the mouse model to highlight the importance of WDR1 and actin regulation in the activation of the inflammasome, and in human autoinflammation.
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