ArticleThe Journal of experimental medicine2021
Nfkb2 variants reveal a p100-degradation threshold that defines autoimmune susceptibility.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Human inborn errors of the alternative NF-κB pathway.Journal of human immunity · 2026Review
- Comprehensive αβ T-Cell Receptor Repertoire Analysis Reveals a Unique CD8+ TCR Landscape in DOCK8-Deficient Patients.Allergy · 2025Article
- Case report: novel NFKB2 variant associated with pediatric eosinophilic granulomatosis with polyangiitis (EGPA) in the COVID-19 pandemic.Pediatric rheumatology online journal · 2025Article
- Thymic inborn errors of immunity.The Journal of allergy and clinical immunology · 2025Review
- Intrinsic functional defects in B cells of patients with NFKB2 mutations.Clinical and experimental immunology · 2025Article
- Modeling corticotroph deficiency with pituitary organoids supports the functional role ofeLife · 2024Article
- Article
- Autoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency.Nature · 2023Article
- Mistuned NF-κB signaling in lymphocytes: lessons from relevant inborn errors of immunity.Clinical and experimental immunology · 2023Article
- NFKB2 haploinsufficiency identified via screening for IFN-α2 autoantibodies in children and adolescents hospitalized with SARS-CoV-2-related complications.The Journal of allergy and clinical immunology · 2023Article
- [Development of autoimmunity in patients with primary immunodeficiencies].Revista medica del Instituto Mexicano del Seguro Social · 2023Article
- Editorial: Non-canonical NF-κB signaling in immune-mediated inflammatory diseases and malignancies.Frontiers in immunology · 2023Article
- Altered mRNA Expression of NFKB1 and NFKB2 Genes in Penile Lichen Sclerosus, Penile Cancer and Zoon Balanitis.Journal of clinical medicine · 2022Article
- Skin manifestations of inborn errors of NF-κB.Frontiers in pediatrics · 2022Review
- How Thymocyte Deletion in the Cortex May Curtail Antigen-Specific T-Regulatory Cell Development in the Medulla.Frontiers in immunology · 2022Article
- Combined immunodeficiency with autoimmunity caused by a homozygous missense mutation in inhibitor of nuclear factor 𝛋B kinase alpha (IKKα).Science immunology · 2021Article
- Current and Future Therapeutic Approaches for Thymic Stromal Cell Defects.Frontiers in immunology · 2021Review
- Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy.Frontiers in pediatrics · 2021Review
- The noncanonical NFκB pathway: Regulatory mechanisms in health and disease.WIREs mechanisms of diseaseReview
Corrections and comments
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Authors and funding
25 authors at 8 institutions in 3 countries.
Funding
Abstract
NF-κB2/p100 (p100) is an inhibitor of κB (IκB) protein that is partially degraded to produce the NF-κB2/p52 (p52) transcription factor. Heterozygous NFKB2 mutations cause a human syndrome of immunodeficiency and autoimmunity, but whether autoimmunity arises from insufficiency of p52 or IκB function of mutated p100 is unclear. Here, we studied mice bearing mutations in the p100 degron, a domain that harbors most of the clinically recognized mutations and is required for signal-dependent p100 degradation. Distinct mutations caused graded increases in p100-degradation resistance. Severe p100-degradation resistance, due to inheritance of one highly degradation-resistant allele or two subclinical alleles, caused thymic medullary hypoplasia and autoimmune disease, whereas the absence of p100 and p52 did not. We inferred a similar mechanism occurs in humans, as the T cell receptor repertoires of affected humans and mice contained a hydrophobic signature of increased self-reactivity. Autoimmunity in autosomal dominant NFKB2 syndrome arises largely from defects in nonhematopoietic cells caused by the IκB function of degradation-resistant p100.
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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.