ArticleNature immunology2021
A variant in human AIOLOS impairs adaptive immunity by interfering with IKAROS.
Article in Nature immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Leveraging pleiotropy identifies common-variant associations with selective IgA deficiency.Clinical immunology (Orlando, Fla.) · 2024Pooled it
- Safety considerations for cereblon-recruiting targeted protein degraders.Nature reviews. Drug discovery · 2026Review
- Exome sequencing enables molecular diagnosis in 10% of early-onset or familial systemic lupus erythematosus cases.EBioMedicine · 2026Article
- Fatal Systemic Granulomatous Disease Associated with Vaccine-Derived Rubella Virus in AIOLOS-Associated Immunodeficiency.Journal of clinical immunology · 2026Article
- Reprogramming lineage features promotes epithelial behavior in carcinoma cells.Cancer letters · 2026Article
- Article
- Aiolos restricts the generation of antigen-inexperienced, virtual memory CD8Nature communications · 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
- Human immunity.Journal of human immunity · 2025Article
- A Germline Heterozygous Dominant Negative IKZF2 Variant Causing Syndromic Primary Immune Regulatory Disorder and ICHAD.Journal of clinical immunology · 2025Article
- Mapping the genetic landscape of immune-mediated disorders: potential implications for classification and therapeutic strategies.Frontiers in immunology · 2025Article
- Inborn errors of immunity caused by dominant negative interference by a BCL11B variant.Nature immunology · 2024Article
- A mutant BCL11B-N440K protein interferes with BCL11A function during T lymphocyte and neuronal development.Nature immunology · 2024Article
- Cell-type specific, inducible and acute degradation of targeted protein in mice by two degron systems.Nature communications · 2024Article
- Aiolos promotes CXCR3 expression on Th1 cells via positive regulation of IFN-γ/STAT1 signaling.JCI insight · 2024Article
- Exome variant prioritization in a large cohort of hearing-impaired individuals indicates IKZF2 to be associated with non-syndromic hearing loss and guides future research of unsolved cases.Human genetics · 2024Article
- Exploring the oncogenic potential of Aiolos in lung cancer through OTUB1-mediated ubiquitination.Heliyon · 2024Article
- AIOLOS-Associated Inborn Errors of Immunity.Journal of clinical immunology · 2024Review
- Identification and Functional Analysis of a de novo IKZF3 Mutation in a Pediatric Patient with Combined Immunodeficiency.Journal of clinical immunology · 2024Article
Corrections and comments
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Authors and funding
20 authors at 10 institutions in 3 countries.
Funding
Abstract
In the present study, we report a human-inherited, impaired, adaptive immunity disorder, which predominantly manifested as a B cell differentiation defect, caused by a heterozygous IKZF3 missense variant, resulting in a glycine-to-arginine replacement within the DNA-binding domain of the encoded AIOLOS protein. Using mice that bear the corresponding variant and recapitulate the B and T cell phenotypes, we show that the mutant AIOLOS homodimers and AIOLOS-IKAROS heterodimers did not bind the canonical AIOLOS-IKAROS DNA sequence. In addition, homodimers and heterodimers containing one mutant AIOLOS bound to genomic regions lacking both canonical motifs. However, the removal of the dimerization capacity from mutant AIOLOS restored B cell development. Hence, the adaptive immunity defect is caused by the AIOLOS variant hijacking IKAROS function. Heterodimeric interference is a new mechanism of autosomal dominance that causes inborn errors of immunity by impairing protein function via the mutation of its heterodimeric partner.
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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.