ArticleThe Journal of allergy and clinical immunology2018
Loss-of-function nuclear factor κB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans.
Article in The Journal of allergy and clinical immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers, 2 of them syntheses that pooled it.
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Who cites it
125 citing papers in PubMed, 2 syntheses or guidelines pooled it, 228 citations in OpenAlex.
- Large-scale GWAS meta-analysis of serum antibody levels in healthy individuals reveals distinct genetic architectures.Genes and immunity · 2026Pooled it
- Clinical, Immunological, and Genetic Features in Patients with NFKB1 and NFKB2 Mutations: a Systematic Review.Journal of clinical immunology · 2024Pooled it
- Genetic Heterogeneity of Inborn Errors of Immunity Revealed by Whole-Genome Sequencing: Insights from a Russian Patient Cohort.International journal of molecular sciences · 2026Article
- From Undifferentiated Connective Tissue Disease to Common Variable Immunodeficiency: A Novel NFKB1 Mutation in a Pediatric Case.Clinical case reports · 2026Article
- Beyond B cells: T and Innate Immune Mechanisms of Autoimmunity in Common Variable Immunodeficiency.Clinical reviews in allergy & immunology · 2026Review
- A Detrimental NFKB2 Missense Variant is Associated with Hypogammaglobulinemia.Journal of clinical immunology · 2026Article
- Rare variants in genes related to inborn errors of immunity in patients with rheumatoid arthritis and secondary immunodeficiency.RMD open · 2026Article
- Genetic testing guides therapy in children with refractory cytopenias.Haematologica · 2026Article
- Article
- Heterozygous NFKB1 variant causes inflammatory dysregulation shaped by broader genetic context in common variable immunodeficiency.JCI insight · 2026Article
- Porto-sinusoidal Vascular Disease is Associated with Gastrointestinal Disorders in Common Variable Immunodefiency.Journal of clinical immunology · 2026Article
- A systematic literature review of CVID reveals pervasive detrimental noninfectious manifestations.Journal of human immunity · 2026Article
- Clinical and immunological characterization ofFrontiers in immunology · 2026Article
- A multidisciplinary RNA-guided approach to complement genomic analysis of unsolved patients with an inborn error of immunity.Frontiers in immunology · 2026Article
- Defective Function of Inhibitor of κB Kinase Subunit Beta Associated With Multiple Immune-Mediated Disorders.Experimental dermatology · 2026Article
- The Presentation, Diagnosis, and Management of Autosomal Dominant Common Variable Immunodeficiency Type XII with NFKB1 Mutation and Autoimmune Neutropenia Treated with Allogenic Stem Cell Transplantation.Hematology reports · 2025Article
- Genetics in a Danish Common Variable Immunodeficiency Cohort.Journal of clinical immunology · 2025Article
- The Burden of Non-Infectious Organ-Specific Immunopathology in Pediatric Common Variable Immunodeficiency.International journal of molecular sciences · 2025Review
- Common Variable Immunodeficiency Clinical Manifestations Are Shaped by Presence and Type of Heterozygous NFKB1 Variants.The journal of allergy and clinical immunology. In practice · 2025Article
- Case Report: A novel CXCR4 variant (p.S341Y) in a family with a pathogenic NFKB1 variant and variable clinical manifestations.Frontiers in immunology · 2025Article
65 more citing papers are in PubMed but not listed here.
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Authors and funding
31 authors at 11 institutions in 3 countries.
Funding
Abstract
backgroundThe genetic cause of primary immunodeficiency disease (PID) carries prognostic information.
objectiveWe conducted a whole-genome sequencing study assessing a large proportion of the NIHR BioResource-Rare Diseases cohort.
methodsIn the predominantly European study population of principally sporadic unrelated PID cases (n = 846), a novel Bayesian method identified nuclear factor κB subunit 1 (NFKB1) as one of the genes most strongly associated with PID, and the association was explained by 16 novel heterozygous truncating, missense, and gene deletion variants. This accounted for 4% of common variable immunodeficiency (CVID) cases (n = 390) in the cohort. Amino acid substitutions predicted to be pathogenic were assessed by means of analysis of structural protein data. Immunophenotyping, immunoblotting, and ex vivo stimulation of lymphocytes determined the functional effects of these variants. Detailed clinical and pedigree information was collected for genotype-phenotype cosegregation analyses.
resultsBoth sporadic and familial cases demonstrated evidence of the noninfective complications of CVID, including massive lymphadenopathy (24%), unexplained splenomegaly (48%), and autoimmune disease (48%), features prior studies correlated with worse clinical prognosis. Although partial penetrance of clinical symptoms was noted in certain pedigrees, all carriers have a deficiency in B-lymphocyte differentiation. Detailed assessment of B-lymphocyte numbers, phenotype, and function identifies the presence of an increased CD21
conclusionWe show that heterozygous loss-of-function variants in NFKB1 are the most common known monogenic cause of CVID, which results in a temporally progressive defect in the formation of immunoglobulin-producing B cells.
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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.