Evidence map›Paper›PMID 29518426›Full record

ArticleThe Journal of allergy and clinical immunology2018

CD40 ligand deficiency causes functional defects of peripheral neutrophils that are improved by exogenous IFN-γ.

Otavio Cabral-Marques, Tabata Takahashi França, Ashraf Al-Sbiei, Lena Friederike Schimke, Taj Ali Khan, Claudia Feriotti, Tania Alves da Costa, Osvaldo Reis Junior, Cristina Worm Weber, Janaíra Fernandes Ferreira and 16 more

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

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 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

13 citing papers in PubMed, 24 citations in OpenAlex.

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  5. Understanding neutropenia secondary to intrinsic or iatrogenic immune dysregulation.Hematology. American Society of Hematology. Education Program · 2021
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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

26 authors at 12 institutions in 6 countries.

Otavio Cabral-MarquesDepartment of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; Department of Rheumatology, University Lübeck, Lübeck, Germany.
Tabata Takahashi FrançaDepartment of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Ashraf Al-SbieiDepartment of Medical Microbiology & Immunology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
Lena Friederike SchimkeDepartment of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; Department of Rheumatology, University Lübeck, Lübeck, Germany.
Taj Ali KhanDepartment of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; Department of Microbiology, Kohat University of Science and Technology, Kohat, Pakistan.
Claudia FeriottiDepartment of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Tania Alves da CostaDepartment of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Osvaldo Reis JuniorCentral Laboratory of High Performance Technologies (LaCTAD), State University of Campinas, Campinas, Brazil.
Cristina Worm WeberPediatric Allergy & Immunology Clinic, Caxias do Sul, Brazil.
Janaíra Fernandes FerreiraAlbert Sabin Hospital, Fortaleza, Brazil.
Fabiola Scancetti TavaresPediatric Immunology Clinic, Unit of Pediatrics, Hospital de Base do Distrito Federal, Asa Sul, Brazil.
Claudia ValentePediatric Immunology Clinic, Unit of Pediatrics, Hospital de Base do Distrito Federal, Asa Sul, Brazil.
Regina Sumiko Watanabe Di GesuDivision of Allergy and Immunology, Department of Pediatrics, Conceicão Children Hospital, Porto Alegre, Brazil.
Asif IqbalDepartment of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil.
Gabriela RiemekastenDepartment of Rheumatology, University Lübeck, Lübeck, Germany.
Gustavo Pessini Amarante-MendesDepartment of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
José Alexandre Marzagão BarbutoDepartment of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; Cell and Molecular Therapy Center, NETCEM, University of São Paulo, São Paulo, Brazil.
Beatriz Tavares Costa-CarvalhoDivision of Allergy-Immunology and Rheumatology, Department of Pediatrics, Federal University of São Paulo, São Paulo, Brazil.
Paulo Vitor Soeiro PereiraDepartment of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; Department of Pathology, Federal University of Maranhao, São Luis, Brazil.
Maria J Fernandez-CabezudoDepartment of Biochemistry, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
Vera Lucia Garcia CalichDepartment of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Luigi D NotarangeloLaboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
Troy R TorgersonDepartment of Pediatrics, University of Washington School of Medicine, and Seattle Children's Research Institute, Seattle, Wash.
Basel K Al-RamadiDepartment of Medical Microbiology & Immunology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
Hans D OchsDepartment of Pediatrics, University of Washington School of Medicine, and Seattle Children's Research Institute, Seattle, Wash.
Antonio Condino-NetoDepartment of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Electronic address: antoniocondino@gmail.com.
Universidade de São Paulo · BRUnited Arab Emirates University · AEHospital de Base · BRSeattle Children's Hospital · USGrupo Hospitalar Conceição · BRHospital Infantil Albert Sabin · BRKohat University of Science and Technology · PKNational Institutes of Health · USUniversidade de Caxias do Sul · BRUniversidade Estadual de Campinas (UNICAMP) · BRUniversidade Federal de São Paulo · BRUniversity of Lübeck · DE

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 Z99 AI999999NULL Z99 AI999999
6 · The paper itself

Abstract

backgroundPatients with X-linked hyper-IgM syndrome caused by CD40 ligand (CD40L) deficiency often present with episodic, cyclic, or chronic neutropenia, suggesting abnormal neutrophil development in the absence of CD40L-CD40 interaction. However, even when not neutropenic and despite immunoglobulin replacement therapy, CD40L-deficient patients are susceptible to life-threatening infections caused by opportunistic pathogens, suggesting impaired phagocyte function and the need for novel therapeutic approaches.

objectivesWe sought to analyze whether peripheral neutrophils from CD40L-deficient patients display functional defects and to explore the in vitro effects of recombinant human IFN-γ (rhIFN-γ) on neutrophil function.

methodsWe investigated the microbicidal activity, respiratory burst, and transcriptome profile of neutrophils from CD40L-deficient patients. In addition, we evaluated whether the lack of CD40L in mice also affects neutrophil function.

resultsNeutrophils from CD40L-deficient patients exhibited defective respiratory burst and microbicidal activity, which were improved in vitro by rhIFN-γ but not soluble CD40L. Moreover, neutrophils from patients showed reduced CD16 protein expression and a dysregulated transcriptome suggestive of impaired differentiation. Similar to CD40L-deficient patients, CD40L knockout mice were found to have impaired neutrophil responses. In parallel, we demonstrated that soluble CD40L induces the promyelocytic cell line HL-60 to proliferate and mature by regulating the expression of genes of the same Gene Ontology categories (eg, cell differentiation) when compared with those dysregulated in peripheral blood neutrophils from CD40L-deficient patients.

conclusionOur data suggest a nonredundant role of CD40L-CD40 interaction in neutrophil development and function that could be improved in vitro by rhIFN-γ, indicating a potential novel therapeutic application for this cytokine.

Indexed as

AnimalsCD40 LigandFemaleHL-60 CellsHumansHyper-IgM Immunodeficiency Syndrome, Type 1Interferon-gammaMice, Inbred C57BLMice, KnockoutNeutrophilsN-Formylmethionine Leucyl-PhenylalanineParacoccidioidesReactive Oxygen SpeciesRecombinant ProteinsRespiratory BurstStaphylococcus aureusCD40 LigandInterferon-gammaN-Formylmethionine Leucyl-PhenylalanineReactive Oxygen SpeciesRecombinant ProteinsTetradecanoylphorbol AcetateCD40 ligandcell developmentIFN-γNeutrophils

Identifiers

PMID29518426
PMCPMC6123297
OpenAlexW2793916764

What OpenQuestion holds

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LicenceTDM
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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.