Journal article
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
Disease Systems Immunology, Section for Protein Science and Biotherapeutics, Department of Biotechnology and Biomedicine, Technical University of Denmark1
Department of Biotechnology and Biomedicine, Technical University of Denmark2
University of Copenhagen3
National Food Institute, Technical University of Denmark4
Research Group for Food Allergy, National Food Institute, Technical University of Denmark5
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.
| Language: | English |
|---|---|
| Publisher: | Elsevier |
| Year: | 2019 |
| Pages: | 587-593 |
| ISSN: | 23523964 |
| Types: | Journal article |
| DOI: | 10.1016/j.ebiom.2019.04.047 |
| ORCIDs: | Larsen, Jeppe Madura , Brix Pedersen, Susanne , Thysen, Anna Hammerich , 0000-0003-4131-7592 , 0000-0001-7431-5206 and 0000-0001-6846-6243 |
Age Factors Allergens Bacteria Bacterial Infections COPSAC, Copenhagen Prospective Studies on Asthma in Childhood Cohort Studies Cytokines Disease Susceptibility Female Humans Immunization Immunoglobulin E Immunophenotyping Infant Infant, Newborn Interleukin-2 Leukocytes, Mononuclear Male Medicine Medicine (General) PBMC, Peripheral Blood Mononuclear Cell PCA, Principal Component Analysis R R5-920 Rhinitis, Allergic SPT, Skin prick test T-Lymphocyte Subsets Treg, regulatory T cell
