Evidence map›Paper›PMID 25312759›Full record

ArticleThe Journal of allergy and clinical immunology2015

An inherited immunoglobulin class-switch recombination deficiency associated with a defect in the INO80 chromatin remodeling complex.

Sven Kracker, Michela Di Virgilio, Jeremy Schwartzentruber, Cyrille Cuenin, Monique Forveille, Marie-Céline Deau, Kevin M McBride, Jacek Majewski, Anna Gazumyan, Suranjith Seneviratne and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of allergy and clinical immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.9field-weighted citation impact, top 15% of its field
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.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 48 citations in OpenAlex.

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  9. Epigenetic Priming in Immunodeficiencies.Frontiers in cell and developmental biology · 2019
    Review
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  15. Advances in clinical immunology in 2015.The Journal of allergy and clinical immunology · 2016
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 8 institutions in 5 countries.

Sven KrackerINSERM UMR 1163, The Human Lymphohematopoiesis Laboratory, Imagine Institute, Paris, France; Paris Descartes Sorbonne Paris Cité University, Imagine Institute, Paris, France.
Michela Di VirgilioLaboratory of Molecular Immunology, Howard Hughes Medical Institute, the Rockefeller University, New York, NY.
Jeremy SchwartzentruberDepartment of Human Genetics, McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada.
Cyrille CueninInternational Agency for Research on Cancer, F-69008 Lyon, Lyon, France.
Monique ForveilleCenter for Primary Immunodeficiencies, Hôpital Necker Enfants Malades, F-75015 Paris, Paris, France.
Marie-Céline DeauINSERM UMR 1163, The Human Lymphohematopoiesis Laboratory, Imagine Institute, Paris, France; Paris Descartes Sorbonne Paris Cité University, Imagine Institute, Paris, France.
Kevin M McBrideLaboratory of Molecular Immunology, Howard Hughes Medical Institute, the Rockefeller University, New York, NY.
Jacek MajewskiDepartment of Human Genetics, McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada.
Anna GazumyanLaboratory of Molecular Immunology, Howard Hughes Medical Institute, the Rockefeller University, New York, NY.
Suranjith SeneviratneUCL Institute of Immunity and Transplantation, Royal Free London NHS Foundation Tust, London, United Kingdom.
Bodo GrimbacherUCL Institute of Immunity and Transplantation, Royal Free London NHS Foundation Tust, London, United Kingdom; Centre of Chronic Immunodeficiency, University Medical Center Freiburg and University of Freiburg, D-79106 Freiburg, Freiburg, Germany.
Necil KutukculerEge University Faculty of Medicine, Department of Pediatric Immunology, 35100 Bornova, Izmir, Turkey.
Zdenko HercegInternational Agency for Research on Cancer, F-69008 Lyon, Lyon, France.
Marina CavazzanaINSERM UMR 1163, The Human Lymphohematopoiesis Laboratory, Imagine Institute, Paris, France; Paris Descartes Sorbonne Paris Cité University, Imagine Institute, Paris, France; Department of Biotherapy, AP-HP Hôpital Necker Enfants Malades, F-75015 Paris, Paris, France; Clinical Investigation Center (CIC)-Biotherapy GHU Ouest, INSERM-APHP (Assistance Publique des Hôpitaux de Paris), Paris, France.
Nada JabadoDepartment of Pediatrics, McGill University and McGill University Health Center, Montreal, Quebec, Canada.
Michel C NussenzweigLaboratory of Molecular Immunology, Howard Hughes Medical Institute, the Rockefeller University, New York, NY.
Alain FischerINSERM UMR 1163, The Human Lymphohematopoiesis Laboratory, Imagine Institute, Paris, France; Paris Descartes Sorbonne Paris Cité University, Imagine Institute, Paris, France; Department of Immunology and Hematology, Hôpital Necker Enfants Malades, F-75015 Paris, Paris, France; Collège de France, Paris, France.
Anne DurandyINSERM UMR 1163, The Human Lymphohematopoiesis Laboratory, Imagine Institute, Paris, France; Paris Descartes Sorbonne Paris Cité University, Imagine Institute, Paris, France; Department of Immunology and Hematology, Hôpital Necker Enfants Malades, F-75015 Paris, Paris, France. Electronic address: anne.durandy@inserm.fr.
Inserm · FRCentre International de Recherche sur le Cancer · FRMcGill University and Génome Québec Innovation Centre · CAEge University · TRHôpital Necker-Enfants Malades · FRSorbonne Paris Cité · FRUniversity College London · GBUniversity of Freiburg · DE

Funding

Class Switch Recombination in B LymphocytesR37AI037526 · NIAID · ROCKEFELLER UNIVERSITY · PI NUSSENZWEIG, MICHEL C · 2014 to 2023
$5.4M
SIGNALLING PATHWAYS IN AUTOIMMUNITYR01AI037526 · NIAID · ROCKEFELLER UNIVERSITY · PI NUSSENZWEIG, MICHEL C · 1994 to 2012
$5.0M
European Research Council 249816NIAID NIH HHS R01 AI037526NIAID NIH HHS R37 AI037526World Health Organization 001
6 · The paper itself

Abstract

backgroundImmunoglobulin class-switch recombination defects (CSR-D) are rare primary immunodeficiencies characterized by impaired production of switched immunoglobulin isotypes and normal or elevated IgM levels. They are caused by impaired T:B cooperation or intrinsic B cell defects. However, many immunoglobulin CSR-Ds are still undefined at the molecular level.

objectiveThis study's objective was to delineate new causes of immunoglobulin CSR-Ds and thus gain further insights into the process of immunoglobulin class-switch recombination (CSR).

methodsExome sequencing in 2 immunoglobulin CSR-D patients identified variations in the INO80 gene. Functional experiments were performed to assess the function of INO80 on immunoglobulin CSR.

resultsWe identified recessive, nonsynonymous coding variations in the INO80 gene in 2 patients affected by defective immunoglobulin CSR. Expression of wild-type INO80 in patients' fibroblastic cells corrected their hypersensitivity to high doses of γ-irradiation. In murine CH12-F3 cells, the INO80 complex accumulates at Sα and Eμ regions of the IgH locus, and downregulation of INO80 as well as its partners Reptin and Pontin impaired CSR. In addition, Reptin and Pontin were shown to interact with activation-induced cytidine deaminase. Finally, an abnormal separation of sister chromatids was observed upon INO80 downregulation in CH12-F3 cells, pinpointing its role in cohesin activity.

conclusionINO80 deficiency appears to be associated with defective immunoglobulin CSR. We propose that the INO80 complex modulates cohesin function that may be required during immunoglobulin switch region synapsis.

Indexed as

Chromatin Assembly and DisassemblyGene RearrangementImmunoglobulin Class SwitchingATPases Associated with Diverse Cellular ActivitiesCarrier ProteinsCell Cycle ProteinsCell LineCell SurvivalChromosomal Proteins, Non-HistoneCohesinsDNA-Binding ProteinsDNA HelicasesDNA RepairGene Expression RegulationGenetic VariationHumansATPases Associated with Diverse Cellular ActivitiesCarrier ProteinsCell Cycle ProteinsChromosomal Proteins, Non-HistoneCohesinsDNA-Binding ProteinsDNA HelicasesImmunoglobulin IsotypesINO80 protein, humanRUVBL1 protein, humanRUVBL2 protein, humanChromatin remodelingclass-switch recombination defectcohesinCSR synapse

Identifiers

PMID25312759
PMCPMC4382329
OpenAlexW2093660931

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

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.