Dataset Information

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

ABSTRACT:

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-year-old (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-?, 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_H1 frequencies were significantly lower in infants with AD versus all older patients (P < .01), frequencies of CLA⁺ T_H2 T cells were similarly expanded across all AD age groups compared with control subjects (P < .05). After infancy, CLA^- T_H2 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.

SUBMITTER: Czarnowicki T

PROVIDER: S-EPMC6957229 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Czarnowicki Tali T He Helen H Canter Talia T Han Joseph J Lefferdink Rachel R Erickson Taylor T Rangel Stephanie S Kameyama Naoya N Kim Hyun Je HJ Pavel Ana B AB Estrada Yeriel Y Krueger James G JG Paller Amy S AS Guttman-Yassky Emma E

The Journal of allergy and clinical immunology 20191015 1

<h4>Background</h4>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.<h4>Objective</h4>We sought to compare immune activation and cytokine polarization in the blood of 0- to 5-year-old (n = 39), 6- to 11-year-old (n = 26), 12- to 17-year-old (n = 21) and 18-year-old or older (n = 43) patients with AD versus age-matched control ...[more]

PMID: 31626841

Similar Datasets

Project description:ObjectiveDescribe the pattern of atopic disease prevalence from infancy to adulthood.DesignCross-sectional household survey.SettingCommunity-based demographic surveillance site, Mirzapur, Bangladesh.Participants7275 individuals in randomly selected clusters within 156 villages.Primary and secondary outcome measuresThe 12-month prevalence of atopic dermatitis (by UK Working Party Criteria (UK criteria) and International Study of Asthma and Allergies in Childhood (ISAAC)), asthma and rhinitis (by ISAAC); disease severity (by ISAAC); history of ever receiving a medical diagnosis.ResultsChildren aged 2 years had the highest prevalence of atopic dermatitis-18.8% (95% CI 15.2% to 22.4%) by UK criteria and 14.9% (95% CI 11.6% to 18.1%) by ISAAC- and asthma (20.1%, 95% CI 16.4% to 23.8%). Prevalence of rhinitis was highest among 25-29 year olds (6.0%, (95% CI% 4.5 to 7.4%). History of a medical diagnosis was lowest for atopic dermatitis (4.0%) and highest for rhinitis (27.3%) and was significantly associated with severe disease compared with those without severe disease for all three conditions (atopic dermatitis: 30.0% vs 11.7%, p=0.015; asthma; 85.0% vs 60.4%, p<0.001; rhinitis: 34.2% vs 7.3%, p<0.001) and having a higher asset-based wealth score for asthma (29.7% (highest quintile) vs 7.5% (lowest quintile), p<0.001) and rhinitis (39.8% vs 12.5%, p=0.003). Prevalence of having >1 condition was highest (36.2%) at 2 years and decreased with age. Having atopic dermatitis (ISAAC) was associated with significantly increased odds ratios (OR) for comorbid asthma (OR 5.56 (95% CI 4.26 to 7.26)] and rhinitis (3.68 (95% CI 2.73 to 4.96)). Asthma and rhinitis were also strongly associated with each other (OR 8.39 (95% CI 6.48 to 10.86)).ConclusionsAtopic disease burden was high in this rural Bangladeshi population. Having one atopic condition was significantly associated with the presence of another. Low incidence of ever obtaining a medical diagnosis highlights an important opportunity to increase availability of affordable diagnosis and treatment options for all age groups.

Project description:BackgroundIdentifying differences and similarities between cutaneous lymphocyte antigen (CLA)(+) polarized T-cell subsets in children versus adults with atopic dermatitis (AD) is critical for directing new treatments toward children.ObjectiveWe sought to compare activation markers and frequencies of skin-homing (CLA(+)) versus systemic (CLA(-)) "polar" CD4 and CD8 T-cell subsets in patients with early pediatric AD, adults with AD, and control subjects.MethodsFlow cytometry was used to measure CD69/inducible costimulator/HLA-DR frequency in memory cell subsets, as well as IFN-γ, IL-13, IL-9, IL-17, and IL-22 cytokines, defining TH1/cytotoxic T (TC) 1, TH2/TC2, TH9/TC9, TH17/TC17, and TH22/TC22 populations in CD4 and CD8 cells, respectively. We compared peripheral blood from 19 children less than 5 years old and 42 adults with well-characterized moderate-to-severe AD, as well as age-matched control subjects (17 children and 25 adults).ResultsSelective inducible costimulator activation (P < .001) was seen in children. CLA(+) TH2 T cells were markedly expanded in both children and adults with AD compared with those in control subjects, but decreases in CLA(+) TH1 T-cell numbers were greater in children with AD (17% vs 7.4%, P = .007). Unlike in adults, no imbalances were detected in CLA(-) T cells from pediatric patients with AD nor were there altered frequencies of TH22 T cells within the CLA(+) or CLA(-) compartments. Adults with AD had increased frequencies of IL-22-producing CD4 and CD8 T cells within the skin-homing population, compared with controls (9.5% vs 4.5% and 8.6% vs 2.4%, respectively; P < .001), as well as increased HLA-DR activation (P < .01).ConclusionsThese data suggest that TH2 activation within skin-homing T cells might drive AD in children and that reduced counterregulation by TH1 T cells might contribute to excess TH2 activation. TH22 "spreading" of AD is not seen in young children and might be influenced by immune development, disease chronicity, or recurrent skin infections.

Dataset Information

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

Background

Objective

Methods

Results

Conclusions

Publications

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

Similar Datasets

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