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

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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:Identifying 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.We 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.Flow cytometry was used to measure CD69/inducible costimulator/HLA-DR frequency in memory cell subsets, as well as IFN-?, 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).Selective 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).These 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.

Project description:ImportanceWith increasing prevalence of atopic dermatitis (AD) and its manifestation in most countries, together with the supporting evidence of the progression to other atopic phenotypes, AD has developed into a worldwide public health concern. The presence of the disease of has increased since the 1950s, but some recent studies suggest a stationary or decreasing trend.ObjectiveTo analyze a nationwide health register based on prescription data to determine the incidence rate (IR) of AD in an entire pediatric population.Design, setting, and participantsAll children resident in Norway younger than 6 years from January 1, 2009, through December 31, 2015, were included in this cohort study. Medical diagnoses and disease-specific medications were used as a proxy for identifying children with AD in this population-based prescription registry study. The prescription study was terminated in 2016. The total number of 295 286 disease-specific prescriptions was analyzed from August 2016 through December 2017. The hypothesis was formulated before, during, and after the data collection.Main outcomes and measuresAll children with a medical diagnosis of AD or eczema based on at least 2 prescriptions of topical corticosteroids or at least 1 prescription of topical calcineurin inhibitors. Incidence rates per person-year (PY) and IR ratios were calculated.ResultsA total of 295 286 disease-specific prescriptions were dispensed to 122 470 children, of whom 63 460 had AD and 56 009 (88.3%) had reimbursed prescriptions and associated AD diagnoses. The annual Norwegian study population (aged <6 years) increased from 357 451 children in 2009 to 373 954 in 2015. The overall IR increased from 0.028 per PY (95% CI, 0.028-0.029 per PY) in 2009 to 0.034 per PY (95% CI, 0.033-0.035 per PY) in 2014. For children younger than 1 year, the IR increased from 0.052 per PY (95% CI, 0.050-0.053 PY) in 2009 to 0.073 per PY (95% CI, 0.071-0.075 per PY) in 2014. In this age group, the IR was 53% higher in boys compared with girls (IR ratio, 1.53; 95% CI, 1.49-1.57; P < .001). The incidence proportion before the age of 6 years was 17.4% (95% CI, 17.2%-17.7%). The primary seasons for the onset of AD were winter and spring.Conclusions and relevanceThis nationwide study suggests an increase in the IR of pediatric AD, especially among children younger than 1 year. This study's findings suggest that increase occurred with a higher IR during winter and spring seasons. Atopic dermatitis had an earlier onset in boys than in girls. During the study period, more than 1 in 6 children younger than 6 years had, at some point, been affected by AD.

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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