Evidence map›Paper›PMID 37004747›Full record

ArticleThe Journal of allergy and clinical immunology2023

Autoimmunity and immunodeficiency associated with monoallelic LIG4 mutations via haploinsufficiency.

Annaïse J Jauch, Olivier Bignucolo, Sayuri Seki, Marie Ghraichy, Ottavia M Delmonte, Valentin von Niederhäusern, Rebecca Higgins, Adhideb Ghosh, Masako Nishizawa, Mariko Tanaka and 27 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of allergy and clinical immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

10 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
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

37 authors at 13 institutions in 7 countries.

Annaïse J JauchImmunodeficiency Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
Olivier BignucoloSwiss Institute of Bioinformatics, Basel, Switzerland.
Sayuri SekiAIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
Marie GhraichyDivision of Immunology and Children's Research Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland.
Ottavia M DelmonteLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
Valentin von NiederhäusernDivision of Immunology and Children's Research Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland.
Rebecca HigginsDivision of Dermatology and Dermatology Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
Adhideb GhoshDivision of Dermatology and Dermatology Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland; Competence Center for Personalized Medicine, University of Zürich/Eidgenössische Technische Hochschule, Zurich, Switzerland.
Masako NishizawaAIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
Mariko TanakaDepartment of Pathology, The University of Tokyo, Tokyo, Japan.
Adrian BaldrichImmunodeficiency Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
Julius KöppenImmunodeficiency Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
Julia R HirsigerTranslational Immunology, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
Robin HupferImmunodeficiency Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
Stephan EhlInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty for Medicine, University of Freiburg, Freiburg, Germany.
Anne Rensing-EhlInstitute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty for Medicine, University of Freiburg, Freiburg, Germany.
Helmut HopferInstitute for Pathology, University Hospital Basel, Basel, Switzerland.
Spasenija Savic PrinceInstitute for Pathology, University Hospital Basel, Basel, Switzerland.
Stephen R DaleyCentre for Immunology and Infection Control, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Queensland.
Florian A MarquardsenImmunodeficiency Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
Benedikt J MeyerImmunodeficiency Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
Michael TammDepartment of Pneumology, University Hospital Basel, Basel, Switzerland.
Thomas D DaikelerDepartment of Rheumatology, University Hospital Basel, Basel, Switzerland; University Center for Immunology, University Hospital Basel, Basel, Switzerland.
Tamara DieschDivision of Pediatric Oncology/Hematology, University Children's Hospital Basel, Basel, Switzerland.
Thomas KühneDivision of Pediatric Oncology/Hematology, University Children's Hospital Basel, Basel, Switzerland.
Arthur HelblingDivision of Allergology and clinical Immunology, Department of Pneumology and Allergology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Caroline BerkemeierDivision Medical Immunology, Laboratory Medicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
Ingmar HeijnenDivision Medical Immunology, Laboratory Medicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
Alexander A NavariniDivision of Dermatology and Dermatology Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland; University Center for Immunology, University Hospital Basel, Basel, Switzerland.
Johannes TrückDivision of Immunology and Children's Research Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland.
Jean-Pierre de VillartayLaboratory of Genome Dynamics in the Immune System, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherché 1163, Université Paris Descartes Sorbonne Paris Cité, Institut Imagine, Paris, France.
Annette OxeniusInstitute of Microbiology, Eidgenössische Technische Hochschule, Zurich, Switzerland.
Christoph T BergerTranslational Immunology, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland; University Center for Immunology, University Hospital Basel, Basel, Switzerland.
Christoph HessUniversity Center for Immunology, University Hospital Basel, Basel, Switzerland; Immunobiology Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
Luigi D NotarangeloLaboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
Hiroyuki YamamotoImmunodeficiency Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland; AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan. Electronic address: h-yamato@niid.go.jp.
Mike RecherImmunodeficiency Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland; University Center for Immunology, University Hospital Basel, Basel, Switzerland. Electronic address: mike.recher@usb.ch.
University of Basel · CHUniversity Hospital of Basel · CHUniversity of Zurich · CHNational Institute of Infectious Diseases · JPNational Institutes of Health · USUniversity Children’s Hospital Basel · CHUniversity of Freiburg · DEBoard of the Swiss Federal Institutes of Technology · CHDélégation Paris 5 · FRQueensland University of Technology · AUSIB Swiss Institute of Bioinformatics · CHThe University of Tokyo · JPUniversity of Bern · CH

Funding

Characterization of the cellular and molecular bases of inborn errors of immunityZIAAI001222 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI NOTARANGELO, LUIGI · 2017 to 2025
$15.2M
Intramural NIH HHS ZIA AI001222
6 · The paper itself

Abstract

backgroundBiallelic mutations in LIG4 encoding DNA-ligase 4 cause a rare immunodeficiency syndrome manifesting as infant-onset life-threatening and/or opportunistic infections, skeletal malformations, radiosensitivity and neoplasia. LIG4 is pivotal during DNA repair and during V(D)J recombination as it performs the final DNA-break sealing step.

objectivesThis study explored whether monoallelic LIG4 missense mutations may underlie immunodeficiency and autoimmunity with autosomal dominant inheritance.

methodsExtensive flow-cytometric immune-phenotyping was performed. Rare variants of immune system genes were analyzed by whole exome sequencing. DNA repair functionality and T-cell-intrinsic DNA damage tolerance was tested with an ensemble of in vitro and in silico tools. Antigen-receptor diversity and autoimmune features were characterized by high-throughput sequencing and autoantibody arrays. Reconstitution of wild-type versus mutant LIG4 were performed in LIG4 knockout Jurkat T cells, and DNA damage tolerance was subsequently assessed.

resultsA novel heterozygous LIG4 loss-of-function mutation (p.R580Q), associated with a dominantly inherited familial immune-dysregulation consisting of autoimmune cytopenias, and in the index patient with lymphoproliferation, agammaglobulinemia, and adaptive immune cell infiltration into nonlymphoid organs. Immunophenotyping revealed reduced naive CD4

conclusionsThis study provides evidence that certain monoallelic LIG4 mutations may cause human immune dysregulation via haploinsufficiency.

Indexed as

DNA LigasesImmunologic Deficiency SyndromesAutoimmunityDNADNA Ligase ATPHaploinsufficiencyHumansMutationDNADNA Ligase ATPDNA LigasesLIG4 protein, humanautosomal dominantDNA damage–autoimmunityDNA ligase 4haploinsufficiencyimmunodeficiencyinborn errors of immunityprimary immunodeficiency

Identifiers

PMID37004747
PMCPMC10529397
OpenAlexW4362507212

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.