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Tytuł:
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Reduced IL-2 response from peripheral blood mononuclear cells exposed to bacteria at 6 months of age is associated with elevated total-IgE and allergic rhinitis during the first 7 years of life.
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Autorzy:
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Wang N; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Gentofte, Denmark; Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark.
Schoos AM; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Gentofte, Denmark.
Larsen JM; National Food Institute, Technical University of Denmark, Lyngby, Denmark.
Brix S; Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark.
Thysen AH; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Gentofte, Denmark; Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark.
Rasmussen MA; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Gentofte, Denmark; Department of Food Science, University of Copenhagen, Copenhagen, Denmark.
Stokholm J; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Gentofte, Denmark.
Bønnelykke K; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Gentofte, Denmark.
Bisgaard H; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Gentofte, Denmark. Electronic address: .
Chawes BL; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Gentofte, Denmark.
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Źródło:
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EBioMedicine [EBioMedicine] 2019 May; Vol. 43, pp. 587-593. Date of Electronic Publication: 2019 May 02.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Original Publication: [Amsterdam] : Elsevier B.V., [2014]-
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MeSH Terms:
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Bacteria/*immunology
Immunoglobulin E/*immunology
Interleukin-2/*metabolism
Leukocytes, Mononuclear/*immunology
Leukocytes, Mononuclear/*metabolism
Rhinitis, Allergic/*etiology
Rhinitis, Allergic/*metabolism
Age Factors ; Allergens/immunology ; Bacterial Infections/complications ; Bacterial Infections/immunology ; Bacterial Infections/microbiology ; Cohort Studies ; Cytokines/metabolism ; Disease Susceptibility ; Female ; Humans ; Immunization ; Immunoglobulin E/blood ; Immunophenotyping ; Infant ; Infant, Newborn ; Male ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism
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References:
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Contributed Indexing:
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Keywords: Airway bacteria; Birth cohort; IL-2; IgE; Sensitization
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Substance Nomenclature:
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0 (Allergens)
0 (Cytokines)
0 (Interleukin-2)
37341-29-0 (Immunoglobulin E)
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Entry Date(s):
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Date Created: 20190507 Date Completed: 20191125 Latest Revision: 20231104
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Update Code:
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20240105
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PubMed Central ID:
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PMC6558232
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DOI:
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10.1016/j.ebiom.2019.04.047
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PMID:
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31056472
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Background: Autoimmunity and allergy have been associated with decreased number and function of regulatory T-cells (Tregs) and low interleukin-2 (IL-2) levels. We aimed to investigate if the release of IL-2 from peripheral blood mononuclear cells (PBMCs) stimulated with pathogenic airway bacteria was associated with development of allergy-outcomes in early childhood.
Methods: PBMCs were isolated at age 6 months in 331 infants from the Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC 2000 ) mother-child cohort, and subsequently stimulated with H. influenzae, M. catarrhalis and S. pneumoniae in in vitro cultures. Levels of cytokines (IL-2, IL-10, IFN-γ, TNF-α, IL-5, IL-13 and IL-17A) were determined in the supernatant by electrochemiluminescence immunoassays. The immune profiles were analyzed for association with development of total-IgE, allergic sensitization and rhinitis during the first 7 years of life using regression models and principal component analysis (PCA).
Findings: An attenuated IL-2 response to stimulation with H. influenzae (p = 0∙011) and M. catarrhalis (p = 0∙027) was associated with elevated total-IgE at age 7, which was confirmed in a multivariate PCA model including all cytokine measurements (PC2, p = 0∙032). An immune profile with both reduced IL-2 and elevated IL-5 was associated with increased risk of allergic rhinitis (PC3, p = 0∙038). We found no associations with development of allergic sensitization.
Interpretation: A reduced IL-2 response from PBMCs exposed to common pathogenic airway bacteria at age 6 months was associated with elevated total-IgE and allergic rhinitis during the first 7 years of life. These findings suggest that suppressed Treg activity in early life may herald onset of allergy in early childhood, which could be a target for low-dose IL-2 trials in the future. FUND: COPSAC is funded by private and public research funds all listed on www.copsac.com.
(Copyright © 2019. Published by Elsevier B.V.)
Comment in: EBioMedicine. 2019 Jul;45:17-18. (PMID: 31255655)
