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

Ni Wang, Ann-Marie M. Schoos, Jeppe Madura Larsen, Susanne Brix Pedersen, Anna Hammerich Thysen, Morten A. Rasmussen, Jakob Stokholm, Klaus Bønnelykke, Hans Bisgaard*, Bo L. Chawes

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

94 Downloads (Pure)

Abstract

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. PBMCs were isolated at age 6 months in 331 infants from the Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC2000) 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). 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. 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.
Original languageEnglish
JournalEBioMedicine
Volume43
Pages (from-to)587-593
Number of pages7
ISSN2352-3964
DOIs
Publication statusPublished - 2019

Keywords

  • Airway bacteria
  • Birth cohort
  • IL-2
  • IgE
  • Sensitization

Cite this

@article{cb7130dcbc224c05baddf442ec7a56f4,
title = "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",
abstract = "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. PBMCs were isolated at age 6 months in 331 infants from the Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC2000) 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). 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. 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.",
keywords = "Airway bacteria, Birth cohort, IL-2, IgE, Sensitization",
author = "Ni Wang and Schoos, {Ann-Marie M.} and Larsen, {Jeppe Madura} and {Brix Pedersen}, Susanne and Thysen, {Anna Hammerich} and Rasmussen, {Morten A.} and Jakob Stokholm and Klaus B{\o}nnelykke and Hans Bisgaard and Chawes, {Bo L.}",
year = "2019",
doi = "10.1016/j.ebiom.2019.04.047",
language = "English",
volume = "43",
pages = "587--593",
journal = "EBioMedicine",
issn = "2352-3964",
publisher = "Elsevier",

}

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. / Wang, Ni; Schoos, Ann-Marie M.; Larsen, Jeppe Madura; Brix Pedersen, Susanne; Thysen, Anna Hammerich; Rasmussen, Morten A.; Stokholm, Jakob; Bønnelykke, Klaus; Bisgaard, Hans ; Chawes, Bo L.

In: EBioMedicine, Vol. 43, 2019, p. 587-593.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - 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

AU - Wang, Ni

AU - Schoos, Ann-Marie M.

AU - Larsen, Jeppe Madura

AU - Brix Pedersen, Susanne

AU - Thysen, Anna Hammerich

AU - Rasmussen, Morten A.

AU - Stokholm, Jakob

AU - Bønnelykke, Klaus

AU - Bisgaard, Hans

AU - Chawes, Bo L.

PY - 2019

Y1 - 2019

N2 - 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. PBMCs were isolated at age 6 months in 331 infants from the Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC2000) 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). 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. 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.

AB - 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. PBMCs were isolated at age 6 months in 331 infants from the Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC2000) 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). 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. 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.

KW - Airway bacteria

KW - Birth cohort

KW - IL-2

KW - IgE

KW - Sensitization

U2 - 10.1016/j.ebiom.2019.04.047

DO - 10.1016/j.ebiom.2019.04.047

M3 - Journal article

VL - 43

SP - 587

EP - 593

JO - EBioMedicine

JF - EBioMedicine

SN - 2352-3964

ER -