Larsen, Jeppe Madura1; Pedersen, Susanne Brix1; Thysen, Anna Hammerich2; Birch, Sune3; Rasmussen, Morten Arendt4; Bisgaard, Hans Flinker3
1 Department of Systems Biology, Technical University of Denmark2 Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark3 Copenhagen University Hospital4 University of Copenhagen
BackgroundAsthma is a highly prevalent chronic lung disease that commonly originates in early childhood. Colonization of neonatal airways with the pathogenic bacterial strains Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae is associated with increased risk of later childhood asthma. We hypothesized that children with asthma have an abnormal immune response to pathogenic bacteria in infancy. ObjectiveWe aimed to assess the bacterial immune response in asymptomatic infants and the association with later development of asthma by age 7 years. MethodsThe Copenhagen Prospective Studies on Asthma in Childhood birth cohort was followed prospectively, and asthma was diagnosed at age 7 years. The immune response to H influenzae, M catarrhalis, and S pneumoniae was analyzed in 292 infants using PBMCs isolated and stored since the age of 6 months. The immune response was assessed based on the pattern of cytokines produced and T-cell activation. ResultsThe immune response to pathogenic bacteria was different in infants with asthma by 7 years of age (P = .0007). In particular, prospective asthmatic subjects had aberrant production of IL-5 (P = .008), IL-13 (P = .057), IL-17 (P = .001), and IL-10 (P = .028), whereas there were no differences in T-cell activation or peripheral T-cell composition. ConclusionsChildren with asthma by school age exhibited an aberrant immune response to pathogenic bacteria in infancy. We propose that an abnormal immune response to pathogenic bacteria colonizing the airways in early life might lead to chronic airway inflammation and childhood asthma.
Journal of Allergy and Clinical Immunology, 2014, Vol 133, Issue 4, p. 1008-1013
COPSAC - Copenhagen Prospective Studies on Asthma in Childhood; FACS - Fluorescence-activated cell sorting; NK - Natural killer; PC - Principal component; PCA - Principal component analysis; TCR - T-cell receptor; Asthma; Bacteria; Bacterial Infections; Child; Child, Preschool; Cytokines; Female; Humans; Infant; Lymphocyte Activation; Male; Phenotype; Prospective Studies; Respiratory Tract Infections; T-Lymphocyte Subsets