ArticleThe Journal of clinical investigation2018
Dominant-negative IKZF1 mutations cause a T, B, and myeloid cell combined immunodeficiency.
Article 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 99 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
99 citing papers in PubMed, 2 syntheses or guidelines pooled it, 164 citations in OpenAlex.
- Cancer Trends in Inborn Errors of Immunity: A Systematic Review and Meta-Analysis.Journal of clinical immunology · 2024Pooled it
- Clinical Courses of IKAROS and CTLA4 Deficiencies: A Systematic Literature Review and Retrospective Longitudinal Study.Frontiers in immunology · 2021Pooled it
- Abnormal SCID Newborn Screening and Spontaneous Recovery Associated with a Novel Haploinsufficiency IKZF1 Mutation.Journal of clinical immunology · 2021Trial
- Beyond B cells: T and Innate Immune Mechanisms of Autoimmunity in Common Variable Immunodeficiency.Clinical reviews in allergy & immunology · 2026Review
- Integrative Multi-Omics Analysis of Multiple Sclerosis Reveals Cell-Type-Specific Regulatory Landscapes and Discordant Methylation-Expression Coupling.International journal of molecular sciences · 2026Article
- Investigation of a methylated BCAT1 and IKZF1 circulating tumour DNA blood test for monitoring treatment response in patients with colorectal cancer.Journal of cancer research and clinical oncology · 2026Article
- Integrated multi-omics analysis: exploring the molecular regulatory mechanisms of HIV infection and identifying the key gene WFDC2.Clinical and experimental medicine · 2026Article
- Cas9eLife · 2026Article
- Systematic functional validation of IKAROS variants from patients and laboratory-generated mutations.Blood advances · 2026Article
- Defining the vascular niche of human adipose tissue across metabolic states.Nature metabolism · 2026Article
- Article
- Inborn errors of regulatory T-cell differentiation and function.The Journal of allergy and clinical immunology · 2025Review
- Dominant negative ADA2 mutations cause ADA2 deficiency in heterozygous carriers.The Journal of experimental medicine · 2025Article
- CVID Enteropathy Associated With Chronic Norovirus Infection: Background, Clinical Features, and Therapeutic Aspects.Reviews in medical virology · 2025Review
- Defining the vascular niche of human adipose tissue across metabolic states.bioRxiv : the preprint server for biology · 2025Article
- IKZF-associated inborn errors of immunity.Journal of human immunity · 2025Review
- Human genetic influences on early B cell development.Journal of human immunity · 2025Review
- Development of PVTX-405 as a potent and highly selective molecular glue degrader of IKZF2 for cancer immunotherapy.Nature communications · 2025Article
- The IKZF1 N159S mutation is associated with poor outcome and a distinct molecular profile in adult patients with AML.British journal of haematology · 2025Article
- Review
39 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
34 authors at 17 institutions in 4 countries.
Funding
Abstract
Ikaros/IKZF1 is an essential transcription factor expressed throughout hematopoiesis. IKZF1 is implicated in lymphocyte and myeloid differentiation and negative regulation of cell proliferation. In humans, somatic mutations in IKZF1 have been linked to the development of B cell acute lymphoblastic leukemia (ALL) in children and adults. Recently, heterozygous germline IKZF1 mutations have been identified in patients with a B cell immune deficiency mimicking common variable immunodeficiency. These mutations demonstrated incomplete penetrance and led to haploinsufficiency. Herein, we report 7 unrelated patients with a novel early-onset combined immunodeficiency associated with de novo germline IKZF1 heterozygous mutations affecting amino acid N159 located in the DNA-binding domain of IKZF1. Different bacterial and viral infections were diagnosed, but Pneumocystis jirovecii pneumonia was reported in all patients. One patient developed a T cell ALL. This immunodeficiency was characterized by innate and adaptive immune defects, including low numbers of B cells, neutrophils, eosinophils, and myeloid dendritic cells, as well as T cell and monocyte dysfunctions. Notably, most T cells exhibited a naive phenotype and were unable to evolve into effector memory cells. Functional studies indicated these mutations act as dominant negative. This defect expands the clinical spectrum of human IKZF1-associated diseases from somatic to germline, from haploinsufficient to dominant negative.
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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.