ArticleThe Journal of allergy and clinical immunology2019
Gain-of-function CEBPE mutation causes noncanonical autoinflammatory inflammasomopathy.
Article in The Journal of allergy and clinical immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 55 citations in OpenAlex.
- Genetic susceptibility ofGlobal medical genetics · 2025Article
- Article
- To the Editor, "CEBPE-Related Immunodeficiency Mimicking Acute Myeloid Leukemia: A Diagnostic Pitfall in Pediatric Autoinflammatory Disease".Journal of clinical immunology · 2025Article
- Review: Utility of mass spectrometry in rare disease research and diagnosis.NPJ genomic medicine · 2025Review
- Pulmonary Aspergillosis and Low HIES Score in a Family with STAT3 N-Terminal Domain Mutation.Journal of clinical immunology · 2025Article
- Genotype-phenotype correlations in specific granule deficiency: loss of DNA-binding ability and impaired nuclear localization cause severe manifestations due to the c.655_665del CEBPE variant.Clinical and experimental immunology · 2025Article
- Nature and nurture: understanding phenotypic variation in inborn errors of immunity.Frontiers in cellular and infection microbiology · 2023Review
- A Novel CEBPE Variant Causes Severe Infections and Profound Neutropenia.Journal of clinical immunology · 2022Article
- Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee.Journal of clinical immunology · 2022Article
- Systemic Autoinflammatory Diseases: A Growing Family of Disorders of Overlapping Immune Dysfunction.Rheumatic diseases clinics of North America · 2022Review
- Inflammasome activation: from molecular mechanisms to autoinflammation.Clinical & translational immunology · 2022Review
- CCAAT/Enhancer-Binding Proteins in Fibrosis: Complex Roles Beyond Conventional Understanding.Research (Washington, D.C.) · 2022Review
- Yersinia remodels epigenetic histone modifications in human macrophages.PLoS pathogens · 2021Article
- Article
- Great balls of fire: activation and signalling of inflammatory caspases.Biochemical Society transactions · 2021Review
- The Ever-Increasing Array of Novel Inborn Errors of Immunity: an Interim Update by the IUIS Committee.Journal of clinical immunology · 2021Review
- Inborn errors of immunity-recent advances in research on the pathogenesis.Inflammation and regeneration · 2021Review
- Neutrophil specific granule and NETosis defects in gray platelet syndrome.Blood advances · 2021Article
- Innate Immune Responses and Pulmonary Diseases.Advances in experimental medicine and biology · 2021Article
- Actin Remodeling Defects Leading to Autoinflammation and Immune Dysregulation.Frontiers in immunology · 2020Review
Corrections and comments
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Authors and funding
32 authors at 8 institutions in 5 countries.
Funding
Abstract
backgroundCCAAT enhancer-binding protein epsilon (C/EBPε) is a transcription factor involved in late myeloid lineage differentiation and cellular function. The only previously known disorder linked to C/EBPε is autosomal recessive neutrophil-specific granule deficiency leading to severely impaired neutrophil function and early mortality.
objectiveThe aim of this study was to molecularly characterize the effects of C/EBPε transcription factor Arg219His mutation identified in a Finnish family with previously genetically uncharacterized autoinflammatory and immunodeficiency syndrome.
methodsGenetic analysis, proteomics, genome-wide transcriptional profiling by means of RNA-sequencing, chromatin immunoprecipitation (ChIP) sequencing, and assessment of the inflammasome function of primary macrophages were performed.
resultsStudies revealed a novel mechanism of genome-wide gain-of-function that dysregulated transcription of 464 genes. Mechanisms involved dysregulated noncanonical inflammasome activation caused by decreased association with transcriptional repressors, leading to increased chromatin occupancy and considerable changes in transcriptional activity, including increased expression of NLR family, pyrin domain-containing 3 protein (NLRP3) and constitutively expressed caspase-5 in macrophages.
conclusionWe describe a novel autoinflammatory disease with defective neutrophil function caused by a homozygous Arg219His mutation in the transcription factor C/EBPε. Mutated C/EBPε acts as a regulator of both the inflammasome and interferome, and the Arg219His mutation causes the first human monogenic neomorphic and noncanonical inflammasomopathy/immunodeficiency. The mechanism, including widely dysregulated transcription, is likely not unique for C/EBPε. Similar multiomics approaches should also be used in studying other transcription factor-associated diseases.
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Registered trials
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