Article in The Journal of experimental medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
2 · The registry
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Quentin RillerLaboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Imagine Institute, University Paris Cité, Paris, France.ORCID 0000-0003-3323-0235
Boris Sorin *Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Imagine Institute, University Paris Cité, Paris, France.ORCID 0000-0002-3443-9201
Charline Courteille *Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Imagine Institute, University Paris Cité, Paris, France.ORCID 0009-0000-7485-9932
Duong Ho-Nhat *Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Imagine Institute, University Paris Cité, Paris, France.ORCID 0009-0000-0722-2800
Tom Le Voyer *Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Imagine Institute, University Paris Cité, Paris, France.ORCID 0000-0002-7253-3135
Jean-Christophe Debray *Laboratory of Molecular Immunology and Signal Transduction, GIGA-Institute, University of Liège, Liège, Belgium.ORCID 0000-0001-6082-1247
Marie-Claude Stolzenberg *Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Imagine Institute, University Paris Cité, Paris, France.ORCID 0000-0001-8026-0360
Muriel Schmutz *Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Imagine Institute, University Paris Cité, Paris, France.ORCID 0009-0002-4769-2422
Olivier Pellé *Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Imagine Institute, University Paris Cité, Paris, France.ORCID 0000-0002-0163-6487
Thomas BecquardNF-κB, Differentiation and Cancer, URP7324, University Paris Cité, Paris, France.ORCID 0009-0007-5728-4859
María Rodrigo RiestraLaboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Imagine Institute, University Paris Cité, Paris, France.ORCID 0009-0000-0362-8109
Mélanie MigaudLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Imagine Institute, University Paris Cité, Paris, France.ORCID 0000-0003-3062-1214
Laure DelageLaboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Imagine Institute, University Paris Cité, Paris, France.ORCID 0000-0002-5235-9985
Marie JeanpierreLaboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Imagine Institute, University Paris Cité, Paris, France.ORCID 0009-0009-2758-6180
Charlotte BoussardLaboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Imagine Institute, University Paris Cité, Paris, France.ORCID 0000-0002-1237-8321
Camille BrunaudLaboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Imagine Institute, University Paris Cité, Paris, France.ORCID 0009-0005-1130-459X
Aude MagérusLaboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Imagine Institute, University Paris Cité, Paris, France.ORCID 0000-0001-7365-699X
Charles BretotNF-κB, Differentiation and Cancer, URP7324, University Paris Cité, Paris, France.ORCID 0009-0008-5947-0679
Victor MichelLaboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Imagine Institute, University Paris Cité, Paris, France.ORCID 0000-0002-7614-4401
Camille RouxLaboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Imagine Institute, University Paris Cité, Paris, France.ORCID 0009-0007-7444-632X
Capucine PicardStudy Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique-Hopitaux de Paris (AP-HP), University Paris Cité , Paris, France.ORCID 0000-0001-8788-5056
Cécile MassonBioinformatic Platform, INSERM UMR 1163, Imagine Institute, University Paris Cité , Paris, France.ORCID 0000-0001-7870-7821
Christine Bole-FeysotGenomic Platform, INSERM UMR 1163, Imagine Institute, University Paris Cité , Paris, France.ORCID 0000-0002-1935-3063
Nicolas CagnardBioinformatic Platform, INSERM UMR 1163, Imagine Institute, University Paris Cité , Paris, France.ORCID 0000-0002-9051-1896
Aurélien CorneauUMS037, PASS, Plateforme de Cytométrie de la Pitié-Salpêtrière CyPS, Sorbonne Université , Paris, France.ORCID 0000-0003-1272-6872
Isabelle MeytsLaboratory for Inborn Errors of Immunity, Department of Microbiology, Immunology and Transplantation, Department of Pediatrics, University Hospitals Leuven, KU Leuven, Leuven, Belgium.ORCID 0000-0003-1214-0302
Véronique BaudNF-κB, Differentiation and Cancer, URP7324, University Paris Cité, Paris, France.ORCID 0000-0002-4090-718X
Jean-Laurent CasanovaLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Imagine Institute, University Paris Cité, Paris, France.ORCID 0000-0002-7782-4169
Emmanuel DejardinLaboratory of Molecular Immunology and Signal Transduction, GIGA-Institute, University of Liège, Liège, Belgium.ORCID 0000-0003-4855-1242
Anne Puel *Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, Imagine Institute, University Paris Cité, Paris, France.ORCID 0000-0003-2603-0323
Cécile Boulanger *Genetics of Autoimmune Diseases and Cancer, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium.ORCID 0000-0002-2969-6131
Bénédicte Neven *Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Imagine Institute, University Paris Cité, Paris, France.ORCID 0000-0001-8941-0935
Frédéric Rieux-Laucat *Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Imagine Institute, University Paris Cité, Paris, France.ORCID 0000-0001-7858-7866
Funding
Genome-wide search for inborn errors of IL-17 immunity underlying chronic mucocutaneous candidiasisR01AI127564 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI Jean-Laurent Casanova · 2017 to 2026
$4.8M
Advancing Science and Practice in the Retail EnvironmentAgence National de la Recherche ANR-10-IAHU-01Agence Nationale de Recherches sur le Sida et les hépatites virales ECTZ275762Battersea & Bowery Advisory GroupBettencourt-Schueller FoundationFisher Center for Alzheimer's Research FoundationFondation ARC pour la Recherche sur le CancerFondation pour la Recherche Médicale EQU202103012670Fonds National de la Recherche Scientifique 40007512Fonds Wetenschappelijk Onderzoek G0B5120NFrench Ministry of Higher Education and ResearchFrench Ministry of Higher Education, Research, and InnovationGrandir-Fonds de solidarité pour l'enfanceHORIZON-HLTH-2021-DISEASE-04 101057100Howard Hughes Medical InstituteImagine InstituteInstitut National de la Santé et de la Recherche MédicaleInstitut National du CancerJBP FoundationJeffrey Modell FoundationMeyer FoundationNIAID NIH HHS R01 AI127564NIH HHS R01AI127564Paris Cité UniversityPharmingRockefeller UniversitySCOR Corporate Foundation for ScienceSociété Nationale Française de Médecine InterneSquare FoundationStavros Niarchos FoundationSt Giles Foundation
6 · The paper itself
Abstract
IKKα, encoded by CHUK, is crucial in the non-canonical NF-κB pathway and part of the IKK complex activating the canonical pathway alongside IKKβ. The absence of IKKα causes fetal encasement syndrome in humans, fatal in utero, while an impaired IKKα-NIK interaction was reported in a single patient and causes combined immunodeficiency. Here, we describe compound heterozygous variants in the kinase domain of IKKα in a female patient with hypogammaglobulinemia, recurrent lung infections, and Hay-Wells syndrome-like features. We showed that both variants were loss-of-function. Non-canonical NF-κB activation was profoundly diminished in stromal and immune cells while the canonical pathway was unexpectedly partially impaired. Reintroducing wt CHUK restored non-canonical NF-κB activation. The patient had neutralizing autoantibodies against type I IFN, akin to non-canonical NF-κB pathway deficiencies. Thus, this is the first case of biallelic CHUK mutations disrupting IKKα kinase function, broadening non-canonical NF-κB defect understanding, and suggesting IKKα's role in canonical NF-κB target gene expression in humans.
Indexed as
I-kappa B KinaseImmunologic Deficiency SyndromesNF-kappa BAgammaglobulinemiaFemaleHEK293 CellsHumansMutationProtein DomainsSignal TransductionCHUK protein, humanI-kappa B KinaseNF-kappa B
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.
Mutations disrupting the kinase domain of IKKα lead to immunodeficiency and immune dysregulation in humans. · full record | OpenQuestion