Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood

Background: The circulating immune phenotype was defined in adults and young children with early atopic dermatitis (AD), but chronologic changes in the blood of infants and children with AD through adolescence have not been explored. Objective: We sought to compare immune activation and cytokine polarization in the blood of 0- to 5-year-old (n = 39), 6- to 11-yearold (n = 26), 12- to 17-year-old (n = 21) and 18-year-old or older (n = 43) patients with AD versus age-matched control subjects. Methods: Flow cytometry was used to measure IFN-gamma, IL-9, IL-13, IL-17, and IL-22 cytokine levels in CD4(+)/CD8(+) T cells, with inducible costimulator molecule and HLA-DR defining midterm and long-term T-cell activation, respectively, within skin-homing/cutaneous lymphocyte antigen (CLA)(+) versus systemic/CLA(-)T cells. Unsupervised clustering differentiated patients based on their blood biomarker frequencies. Results: Although CLA(+)T(H)1 frequencies were significantly lower in infants with AD versus all older patients (P < .01), frequencies of CLA(+)T(H)2 T cells were similarly expanded across all AD age groups compared with control subjects (P < .05). After infancy, CLA(-)T(H)2 frequencies were increased in patients with AD in all age groups, suggesting systemic immune activation with disease chronicity. IL-22 frequencies serially increased from normal levels in infants to highly significant levels in adolescents and adults compared with levels in respective control subjects (P < .01). Unsupervised clustering aligned the AD profiles along an age-related spectrum from infancy to adulthood (eg, inducible costimulator molecule and IL-22). Conclusions: The adult AD phenotype is achieved only in adulthood. Unique cytokine signatures characterizing individual pediatric endotypes might require age-specific therapies. Future longitudinal studies, comparing the profile of patients with cleared versus persistent pediatric AD, might define age-specific changes that predict AD clearance.