ArticleThe Journal of allergy and clinical immunology2020
Characterization of the clinical and immunologic phenotype and management of 157 individuals with 56 distinct heterozygous NFKB1 mutations.
Erratum issuedOpen access · bronzeAbstract read
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Article in The Journal of allergy and clinical immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 76 papers, 3 of them syntheses that pooled it.
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76citing papers in PubMed, 3 pooled it
6.4field-weighted citation impact, top 2% of its field
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Who cites it
76 citing papers in PubMed, 3 syntheses or guidelines pooled it, 122 citations in OpenAlex.
- Cancer Trends in Inborn Errors of Immunity: A Systematic Review and Meta-Analysis.Journal of clinical immunology · 2024Pooled it
- Clinical, Immunological, and Genetic Features in Patients with NFKB1 and NFKB2 Mutations: a Systematic Review.Journal of clinical immunology · 2024Pooled it
- Exploration of the core protein network under endometriosis symptomatology using a computational approach.Frontiers in endocrinology · 2022Pooled 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
- Decoding the shared genetic liability of lower respiratory tract infections via genomic structural equation modeling.BMC pulmonary medicine · 2026Article
- Mice lacking NF-ĸB1 undergo premature ovarian aging.Reproductive biology and endocrinology : RB&E · 2026Article
- BIRC3 (Encoding cIAP2) Variants Result in Dysregulated RIPK1 Signaling Leading to Increased Epithelial Cell Death and Are Associated With Monogenic Crohn's Disease.Gastroenterology · 2026Article
- Behçet's spectrum disorders: genetic and immunological insights into an emerging disease concept.World journal of pediatrics : WJP · 2026Review
- A systematic literature review of CVID reveals pervasive detrimental noninfectious manifestations.Journal of human immunity · 2026Article
- Lymphoproliferation in Inborn Errors of Immunity: Mechanisms, Manifestations and Clinical Management, with a Focus on ALPID.ImmunoTargets and therapy · 2026Review
- Comprehensive Analysis Reveals Potential Molecular Targets in Juvenile Dermatomyositis.Biochemistry research international · 2026Article
- Case Report: Genetically primed hyperinflammation: cytomegalovirus-triggered HLH-like syndrome in an adolescent with a gain-of-function STING1 (p.Arg281Trp) variant with novel autosomal dominant inheritance and atypical presentation.Frontiers in immunology · 2026Article
- Clinical and immunological characterization ofFrontiers in immunology · 2026Article
- Common Variable Immunodeficiency Disorders: A perspective from New Zealand.Clinical reviews in allergy & immunology · 2025Review
- Incomplete penetrance in inborn errors of immunity: A skeleton in the closet-The sequel.Journal of human immunity · 2025Review
- Review
- 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
16 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedCorrigendum.2021
Authors and funding
76 authors at 20 institutions in 22 countries.
Tiziana LorenziniInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia and ASST- Spedali Civili of Brescia, Brescia, Italy.
Manfred FliegaufInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; CIBSS (Centre for Integrative Biological Signalling Studies), University of Freiburg, Freiburg, Germany.
Nils KlammerInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Natalie FredeInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Michele ProiettiInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Alla BulashevskaInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Nadezhda Camacho-OrdonezInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Markku VarjosaloInstitute of Biotechnology, University of Helsinki, Helsinki, Finland.
Matias KinnunenInstitute of Biotechnology, University of Helsinki, Helsinki, Finland.
Esther de VriesLaboratory for Medical Microbiology and Immunology, Elisabeth Tweesteden Hospital, and Department of Tranzo, Tilburg University, Tilburg, The Netherlands.
Jos W M van der MeerDepartment of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
Rohan AmeratungaDepartment of Virology and Immunology and the Department of Clinical Immunology, Auckland City Hospital, Auckland, New Zealand.
Chaim M RoifmanCanadian Centre for Primary Immunodeficiency, Immunogenomic Laboratory, Division of Immunology and Allergy, Department of Pediatrics, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada.
Yael D SchejterCanadian Centre for Primary Immunodeficiency, Immunogenomic Laboratory, Division of Immunology and Allergy, Department of Pediatrics, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada.
Robin KobbeDepartment of Pediatrics, University Medical Centre Hamburg, Hamburg, Germany.
Timo HautalaDepartment of Internal Medicine, Oulu University Hospital, Oulu, Finland.
Faranaz AtschekzeiDivision of Immunology and Rheumatology, Hannover Medical University, Hannover, Germany; RESIST - Cluster of Excellence 2155 to Hanover Medical School, Satellite Center Freiburg, Freiburg, Germany.
Reinhold E SchmidtDivision of Immunology and Rheumatology, Hannover Medical University, Hannover, Germany; RESIST - Cluster of Excellence 2155 to Hanover Medical School, Satellite Center Freiburg, Freiburg, Germany.
Claudia SchröderDivision of Immunology and Rheumatology, Hannover Medical University, Hannover, Germany.
Polina StepenskyBone Marrow Transplantation Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Bella ShadurBone Marrow Transplantation Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Department of Immunology, Garvan Institute of Medical Research, and University of New South Wales, Graduate Research School, Sydney, Australia.
Luis A PedrozaColegio de ciencias de la salud-Hospital de los Valles and Instituto de Microbiología, Universidad San Francisco de Quito, Quito, Ecuador; Department of Pediatrics, Section of Immunology, Allergy, and Rheumatology, Baylor College of Medicine, Houston, Tex.
Michiel van der FlierDepartment of Pediatric Infectious Diseases & Immunology and Nijmegen Institute for Infection, Immunity and Inflammation, Radboud University Medical Centre, Nijmegen, The Netherlands.
Mónica Martínez-GalloImmunology Division, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Research Institute (VHIR), Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona (UAB), Barcelona, Spain; Jeffrey Model Foundation Excellence Center, Barcelona, Spain.
Luis Ignacio Gonzalez-GranadoPrimary Immunodeficiencies Unit, Pediatrics, School of Medicine, Complutense University, 12 de Octubre Health Research Institute (imas12), Madrid, Spain.
Luis M AllendeImmunology Department, Hospital Universitario 12 de Octubre, Madrid, Spain.
Anna ShcherbinaDepartment of Clinical Immunology, Dmitry Rogachev Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
Natalia KuzmenkoDepartment of Clinical Immunology, Dmitry Rogachev Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
Victoria ZakharovaDepartment of Hematopoietic Stem Cell Transplantation, Dmitry Rogachev National Medical and Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
João Farela NevesPrimary Immunodeficiencies Unit, Hospital Dona Estefania, Centro Hospitalar de Lisboa Central, Lisbon, Portugal.
Peter SvecDepartment of Paediatric Haematology and Oncology, Haematopoietic Stem Cell Transplantation Unit, Comenius University Children's Hospital, Bratislava, Slovakia.
Ute FischerDepartment of Paediatric Oncology, Hematology and Clinical Immunology, Center for Child and Adolescent Health, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
Winnie IpDepartment of Immunology and Molecular and Cellular Immunology Unit, Great Ormond Street Hospital & University College London (UCL), Great Ormond Street Institute of Child Health, London, United Kingdom.
Oliver BartschInstitute of Human Genetics, Medical Centre of the Johannes Gutenberg University, Mainz, Germany.
Safa BarışDepartment of Pediatrics, Division of Allergy and Immunology, Marmara University School of Medicine, Istanbul, Turkey.
Christoph KleinDepartment of Pediatrics, Dr von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany.
Raif GehaDivision of Immunology, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Mass.
Janet ChouDivision of Immunology, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Mass.
Mohammed AlosaimiDivision of Immunology, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Mass.
Lauren WeintraubDivisions of Pediatric Hematology/Oncology, Albany Medical Center, Albany, NY.
Kaan BoztugCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Department of Pediatrics and Adolescent Medicine and St Anna Kinderspital and Children's Cancer Research Institute, Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
Tatjana HirschmuglCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Department of Pediatrics and Adolescent Medicine and St Anna Kinderspital and Children's Cancer Research Institute, Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
Maria Marluce Dos Santos VilelaLaboratory of Pediatric Immunology, Center for Investigation in Pediatrics, Faculty of Medical Sciences, University of Campinas - UNICAMP, Campinas, Brazil.
Dirk HolzingerDepartment of Pediatric Hematology-Oncology, University of Duisburg-Essen, Essen, Germany.
Maximilian SeidlCenter for Chronic Immunodeficiency and Molecular Pathology, Department of Pathology, University Medical Center, University of Freiburg, Freiburg, Germany.
Vassilios LougarisPediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia and ASST- Spedali Civili of Brescia, Brescia, Italy.
Alessandro PlebaniPediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia and ASST- Spedali Civili of Brescia, Brescia, Italy.
Laia AlsinaPediatric Allergy and Clinical Immunology Department and Institut de Recerca, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain.
Monica Piquer-GibertPediatric Allergy and Clinical Immunology Department and Institut de Recerca, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain.
Angela Deyà-MartínezPediatric Allergy and Clinical Immunology Department and Institut de Recerca, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain.
Charlotte A SladeDepartment of Clinical Immunology and Allergy, Royal Melbourne Hospital, Melbourne, Australia.
Asghar AghamohammadiResearch Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran.
Hassan AbolhassaniResearch Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran; Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden.
Lennart HammarströmDivision of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden.
Outi KuisminPEDEGO Research Unit, Medical Research Center Oulu, and University of Oulu and Department of Clinical Genetics, Oulu University Hospital, Oulu, Finland.
Merja HelminenTampere Center for Child Health Research, University of Tampere and Tampere University Hospital, Tampere, Finland.
Hana Lango AllenDepartment of Haematology, University of Cambridge, Cambridge, United Kingdom; NHS Blood and Transplant Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.
James E ThaventhiranDepartment of Medicine, University of Cambridge, Cambridge, United Kingdom.
Alexandra F FreemanLaboratory of Clinical Immunology and Microbiology, NIAID, National Institutes of Health, Bethesda, Md.
Matthew CookAustralian National University Medical School and John Curtin School of Medical Research, Australian National University, Acton, Australia; Department of Immunology, Canberra Hospital, Canberra, Australia.
Shahrzad BakhtiarDivision for Pediatric Stem-Cell Transplantation and Immunology, University Hospital Frankfurt, Frankfurt/Main, Germany.
Mette ChristiansenInternational Center for Immunodeficiency Diseases and Department of Clinical Immunology, Aarhus University Hospital Skejby, Aarhus, Denmark.
Charlotte Cunningham-RundlesDivision of Clinical Immunology, Icahn School of Medicine at Mount Sinai, New York, NY.
Niraj C PatelDepartment of Pediatrics, Section of Infectious Disease and Immunology, Levine Children's Hospital, Atrium Health, Charlotte, NC.
William RaeSouthampton NIHR Wellcome Trust Clinical Research Facility and NIHR Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Department of Allergy, Asthma and Clinical Immunology, University Hospital Southampton, Southampton, United Kingdom.
Tim NiehuesDepartment of Pediatric Hematology and Oncology, Helios Klinikum Krefeld, Krefeld, Germany.
Nina BrauerDepartment of Pediatric Hematology and Oncology, Helios Klinikum Krefeld, Krefeld, Germany.
Jaana SyrjänenDepartment of Internal Medicine, Tampere University Hospital, Tampere, Finland.
Mikko R J SeppänenRare Disease Center, New Children's Hospital and Adult immunodeficiency Unit, Inflammation Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Siobhan O BurnsDepartment of Immunology, Royal Free London NHS Foundation Trust, University College London Institute of Immunity and Transplantation, London, United Kingdom.
Paul TuijnenburgEmma Children's Hospital, Amsterdam UMC, University of Amsterdam, Department of Pediatric Immunology, Rheumatology and Infectious diseases, Meibergdreef 9, Amsterdam, The Netherlands.
Taco W KuijpersEmma Children's Hospital, Amsterdam UMC, University of Amsterdam, Department of Pediatric Immunology, Rheumatology and Infectious diseases, Meibergdreef 9, Amsterdam, The Netherlands.
NIHR BioResourceNIHR BioResource, Cambridge University Hospitals, Cambridge Biomedical Campus, Cambridge, United Kingdom.
Klaus WarnatzInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Rheumatology and Clinical Immunology, Center for Chronic Immunodeficiency, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Bodo GrimbacherInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; CIBSS (Centre for Integrative Biological Signalling Studies), University of Freiburg, Freiburg, Germany; RESIST - Cluster of Excellence 2155 to Hanover Medical School, Satellite Center Freiburg, Freiburg, Germany; Institute of Immunology and Transplantation, Royal Free Hospital and University College London, London, United Kingdom; DZIF (German Center for Infection Research) Satellite Center Freiburg, Freiburg, Germany; Rheumatology and Clinical Immunology, Center for Chronic Immunodeficiency, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Electronic address: bodo.grimbacher@uniklinik-freiburg.de.
NIHR BioResource
University of Freiburg · DEEmma Kinderziekenhuis · NLUniversity of Cambridge · GBHospital Sant Joan de Déu Barcelona · ESBoston Children's Hospital · USDmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology · RUHelios Klinikum Krefeld · DENHS Blood and Transplant · GBUniversity of Helsinki · FIAustralian National University · AUAustrian Academy of Sciences · ATComenius University Bratislava · SKKarolinska University Hospital · SELudwig-Maximilians-Universität München · DENational Institutes of Health · USOulu University Hospital · FIRadboud University Nijmegen · NLRoyal Free London NHS Foundation Trust · GBTampere University Hospital · FIUniversity Hospital Southampton NHS Foundation Trust · GB
Funding
Regulation of IgA class switching in the intestinal mucosaP01AI061093 · NIAID · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI CUNNINGHAM-RUNDLES, CHARLOTTE · 2004 to 2021
$29.8MResources to Assist Investigations in Primary Immunodeficiency Diseases (U24)U24AI086037 · NIAID · IMMUNE DEFICIENCY FOUNDATION · PI CUNNINGHAM-RUNDLES, CHARLOTTE · 2010 to 2019
$6.5MMedical Research Council MC_PC_18030Medical Research Council MR/K020919/1Medical Research Council MR/L006197/1NIAID NIH HHS P01 AI061093NIAID NIH HHS U24 AI086037
Abstract
backgroundAn increasing number of NFKB1 variants are being identified in patients with heterogeneous immunologic phenotypes.
objectiveTo characterize the clinical and cellular phenotype as well as the management of patients with heterozygous NFKB1 mutations.
methodsIn a worldwide collaborative effort, we evaluated 231 individuals harboring 105 distinct heterozygous NFKB1 variants. To provide evidence for pathogenicity, each variant was assessed in silico; in addition, 32 variants were assessed by functional in vitro testing of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB) signaling.
resultsWe classified 56 of the 105 distinct NFKB1 variants in 157 individuals from 68 unrelated families as pathogenic. Incomplete clinical penetrance (70%) and age-dependent severity of NFKB1-related phenotypes were observed. The phenotype included hypogammaglobulinemia (88.9%), reduced switched memory B cells (60.3%), and respiratory (83%) and gastrointestinal (28.6%) infections, thus characterizing the disorder as primary immunodeficiency. However, the high frequency of autoimmunity (57.4%), lymphoproliferation (52.4%), noninfectious enteropathy (23.1%), opportunistic infections (15.7%), autoinflammation (29.6%), and malignancy (16.8%) identified NF-κB1-related disease as an inborn error of immunity with immune dysregulation, rather than a mere primary immunodeficiency. Current treatment includes immunoglobulin replacement and immunosuppressive agents.
conclusionsWe present a comprehensive clinical overview of the NF-κB1-related phenotype, which includes immunodeficiency, autoimmunity, autoinflammation, and cancer. Because of its multisystem involvement, clinicians from each and every medical discipline need to be made aware of this autosomal-dominant disease. Hematopoietic stem cell transplantation and NF-κB1 pathway-targeted therapeutic strategies should be considered in the future.
Indexed as
Genetic Association StudiesGenetic Predisposition to DiseaseHeterozygoteMutationPhenotypeAdultAgedAutoimmunityBiological Variation, PopulationBiomarkersDisease ManagementFemaleFluorescent Antibody TechniqueHumansImmunohistochemistryKaplan-Meier EstimateBiomarkersNF-kappa B p50 SubunitNFKB1 protein, humanautosomal dominantcommon variable immunodeficiencyNFKB1 mutationNFKB1 variantNF-κB1-related phenotypereduced penetrance
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