ArticleThe Journal of experimental medicine2023
Human RELA dominant-negative mutations underlie type I interferonopathy with autoinflammation and autoimmunity.
Article in The Journal of experimental medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- Truncating RELA variants drive autoinflammation and autoimmunity by impairing the negative feedback control of NF-κB.JCI insight · 2026Article
- Landscape of Somatic Mutations in a Large Cohort of Chinese Patients With Immune Dysregulations.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Clinical Insights intoGenes · 2026Article
- Network toxicology and multi-omics identify potential interactions between between air pollutants and interferon-related signaling in tuberculosis.Molecular biology reports · 2026Article
- Decoding variants of uncertain significance in systemic autoinflammatory diseases.Nature reviews. Rheumatology · 2026Review
- Sex-dependent interferon signaling contributes to female-biased vulnerability in Alzheimer's disease.Journal of neuroinflammation · 2026Article
- The Small Molecule H89 Facilitates Mesenchymal Stem Cell-derived Extracellular Vesicle Release and Optimizes Therapeutic Efficacy in Liver Regeneration.Journal of extracellular vesicles · 2026Article
- Exome sequencing enables molecular diagnosis in 10% of early-onset or familial systemic lupus erythematosus cases.EBioMedicine · 2026Article
- A Case-Based Literature Review of RELA Associated Inflammatory Diseases.Journal of clinical immunology · 2026Review
- Lymphoproliferation in Inborn Errors of Immunity: Mechanisms, Manifestations and Clinical Management, with a Focus on ALPID.ImmunoTargets and therapy · 2026Review
- Clinical and immunological characterization ofFrontiers in immunology · 2026Article
- Monogenic disorders of the TNF signalling pathway.Nature reviews. Rheumatology · 2026Review
- Case Report: Diverse pediatric phenotypes ofFrontiers in immunology · 2026Article
- RELA Haploinsufficiency Manifesting as an Atypical Phenotype of Crohn's Disease.Inflammatory bowel diseases · 2025Article
- Rheumatologic and Autoimmune Features of Inborn Errors of Immunity: Implications for Diagnosis and Management.Journal of human immunity · 2025Article
- The pathogenesis, clinical presentations and treatment of monogenic systemic vasculitis.Nature reviews. Rheumatology · 2025Review
- Human inborn errors of immunity: 2024 update on the classification from the International Union of Immunological Societies Expert Committee.Journal of human immunity · 2025Article
- NF-κB RelB suppresses the inflammatory gene expression programs of dendritic cells by competing with RelA for binding to target gene promoters.Cell discovery · 2025Article
- Case report and literature review: clinical manifestations and treatment of human RelA deficiency.Frontiers in immunology · 2025Review
- Impaired development of memory B cells and antibody responses in humans and mice deficient in PD-1 signaling.Immunity · 2024Article
Corrections and comments
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Authors and funding
28 authors at 11 institutions in 4 countries.
Funding
Abstract
Inborn errors of the NF-κB pathways underlie various clinical phenotypes in humans. Heterozygous germline loss-of-expression and loss-of-function mutations in RELA underlie RELA haploinsufficiency, which results in TNF-dependent chronic mucocutaneous ulceration and autoimmune hematological disorders. We here report six patients from five families with additional autoinflammatory and autoimmune manifestations. These patients are heterozygous for RELA mutations, all of which are in the 3' segment of the gene and create a premature stop codon. Truncated and loss-of-function RelA proteins are expressed in the patients' cells and exert a dominant-negative effect. Enhanced expression of TLR7 and MYD88 mRNA in plasmacytoid dendritic cells (pDCs) and non-pDC myeloid cells results in enhanced TLR7-driven secretion of type I/III interferons (IFNs) and interferon-stimulated gene expression in patient-derived leukocytes. Dominant-negative mutations in RELA thus underlie a novel form of type I interferonopathy with systemic autoinflammatory and autoimmune manifestations due to excessive IFN production, probably triggered by otherwise non-pathogenic TLR ligands.
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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.