Distinct Immune Phenotypes in Infants Developing Asthma During Childhood

To address whether a deregulated immune response to generic microbial exposures in infancy is associated with later development of asthma.

In this population-based birth cohort, children at 18 months of age had blood samples were analyzed by flow cytometry (n = 552) and ex vivo stimulation (n = 567), resulting in a total of 541 infants with combined data.

Flow cytometry was used to detect relative frequencies of 18 cell subtypes. Whole blood was stimulated for 24 hours with 7 microbial-derived ligands, and 21 cytokines were measured. Using hierarchical clustering techniques, infants were grouped according to similar cytokine responses to identify relationships between innate immune response phenotypes and development of childhood asthma.

In 18-month-old infants, 5–7 different immune response phenotypes were identified. The overall prevalence of asthma was 23% (127 of 541). At age 6 years, 16% had outgrown their asthma diagnosis, which was termed transient asthma, whereas asthma persisted in 7% of children at age 6 years. Infants who developed transient asthma had antiviral responses associated with type 17 cytokine enhancement without concomitant type 1 immune activation. Infants who developed persistent asthma at 6 years of age showed enhanced T_H2 responses (IL-5 and IL-13).

This study of 18-month-old infants demonstrated distinct antiviral, antibacterial, and T cell response phenotypes that were linked to transient or persistent asthma during the first 6 years of life. Inadequate immune response to single-stranded RNA viruses may be a risk factor for the development of transient asthma whereas enhanced T_H2 responses may increase risk for development of persistent childhood asthma.

With the development of targeted biological therapies, personalized medicine is achievable. This, however, requires a sophisticated understanding of asthma characteristics. Traditional asthma phenotyping, which is a description of observable characteristics, does not provide insight regarding underlying mechanisms of disease and is thus of limited utility in predicting response to therapy. In contrast, asthma endotyping characterizes groups based on functional or pathophysiological mechanisms. Defining innate immune responses in at-risk infants, as shown in this study, could therefore help to identify asthma endotypes and to guide personalized strategies for asthma treatment and prevention.