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Background: Our knowledge of etiopathogenesis of atopic dermatitis (AD) is largely derived from skin biopsies, which are associated with pain, scarring and infection. In contrast, tape‐stripping is a minimally invasive, nonscarring technique to collect skin samples. Methods: To construct a global AD skin transcriptomic profile comparing tape‐strips to whole‐skin biopsies, we performed RNA‐seq on tape‐strips and biopsies taken from the lesional skin of 20 moderate‐to‐severe AD patients and the skin of 20 controls. Differentially expressed genes (DEGs) were defined by fold‐change (FCH) ≥2.0 and false discovery rate <0.05. Results: We detected 4104 (2513 Up; 1591 Down) and 1273 (546 Up; 727 Down) DEGs in AD versus controls, in tape‐strips and biopsies, respectively. Although both techniques captured dysregulation of key immune genes, tape‐strips showed higher FCHs for innate immunity (IL‐1B, IL‐8), dendritic cell (ITGAX/CD11C, FCER1A), Th2 (IL‐13, CCL17, TNFRSF4/OX40), and Th17 (CCL20, CXCL1) products, while biopsies showed higher upregulation of Th22 associated genes (IL‐22, S100As) and dermal cytokines (IFN‐γ, CCL26). Itch‐related genes (IL‐31, TRPV3) were preferentially captured by tape‐strips. Epidermal barrier abnormalities were detected in both techniques, with terminal differentiation defects (FLG2, PSORS1C2) better represented by tape‐strips and epidermal hyperplasia changes (KRT16, MKI67) better detected by biopsies. Conclusions: Tape‐strips and biopsies capture overlapping but distinct features of the AD molecular signature, suggesting their respective utility for monitoring specific AD‐related immune, itch, and barrier abnormalities in clinical trials and longitudinal studies. [ABSTRACT FROM AUTHOR]

Background: The mechanisms driving alopecia areata (AA) are still unclear, hindering development of targeted therapeutics. Specific Th2 targeting with dupilumab in AA provides a unique opportunity to dissect its pathogenesis and explore the role of Th2 pathway. Methods: We evaluated changes in scalp biomarkers in AA patients (with and without concomitant atopy) randomized to weekly dupilumab or placebo for 24 weeks, followed by open‐label dupilumab for 24 weeks. Changes in biomarker levels were measured at weeks 12, 24, and 48 and were also correlated with clinical hair regrowth. Results: At week 24, preceding clinical hair regrowth outcomes, only dupilumab‐treated patients presented significant suppression of cellular infiltrates, and multiple Th2‐related, markers (CCL13/MCP‐4, CCL18/PARC, CCL26/eotaxin‐3, CCL24/Eotaxin‐2), coupled with significant upregulation in the hair keratins. Th1‐related suppression was evident later (week 48) when all patients received open‐label dupilumab. Results were more pronounced in atopic AA patients, that showed 48% and 97% improvements in the lesional AA scalp profile at weeks 24 and 48, respectively, while 2% worsening was seen in the placebo arm at week 24. Moreover, placebo‐treated patients presented 54% worsening in hair keratins when compared with baseline at week 24. At week 24, increases in hair keratins showed significant correlations only with decreases in Th2‐related markers. Conclusions: Scalp biomarkers provide evidence of dupilumab efficacy in AA, detected even prior to clinical response, with exclusive correlations between early suppression of Th2 markers and increased hair keratins. These findings strengthen previous reports suggesting a possible role for Th2 cytokines as AA drivers. [ABSTRACT FROM AUTHOR]

Background: Treatment of inflammatory skin diseases, including atopic dermatitis (AD) and psoriasis, is undergoing transformative changes, highlighting the need to develop experimental models of skin inflammation in humans to predict treatment responses. Methods: We topically or intradermally administered four common sensitizers (dust mite (DM), diphencyprone (DPCP), nickel (Ni), and purified protein derivative (PPD)) to the backs of 40 healthy patients and the skin hypersensitivity response was biopsied and evaluated using immunohistochemistry, RNA‐seq, and RT‐PCR. Results: All agents induced strong increases in cellular infiltrates (T‐cells and dendritic cells) as compared to untreated skin (p <.05), with variable T helper polarization. Overall, DPCP induced the strongest immune responses across all pathways, including innate immunity (IL‐1α, IL‐8), Th1 (IFNγ, CXCL10), Th2 (IL‐5, CCL11), and Th17 (CAMP/LL37) products, as well as the highest regulatory tone (FOXP3, IL‐34, IL‐37) (FDR <0.01). Nickel induced Th17 (IL‐17A), Th1 (CXCL10) and Th2 (IL‐4R) immune responses to a lesser extent than DPCP (p <.05). PPD induced predominantly Th1 (IFNγ, CXCL10, STAT1) and Th17 inflammation (IL‐17A) (p <.05). DM induced modulation of Th2 (IL‐13, CCL17, CCL18), Th22 (IL‐22), and Th17/Th22 (S100A7/9/12) pathways (p <.05). Barrier defects that characterize both AD and psoriasis were best modeled by DPCP and Ni, followed by PPD, including downregulation of terminal differentiation (FLG, FLG2, LOR, LCEs), tight junction (CLDN1/CLDN8), and lipid metabolism (FA2H, FABP7)‐related markers. Conclusion: Our data imply that DPCP induced the strongest immune response across all pathways, and barrier defects characteristic of AD and psoriasis. [ABSTRACT FROM AUTHOR]

Background: Treatments for alopecia areata (AA) patients with extensive scalp hair loss are limited, and recent evidence supports a role for type 2 T‐cell (Th2)‐immune response in AA. Dupilumab, a monoclonal antibody inhibiting Th2 signaling, approved for type 2 diseases including atopic dermatitis, was evaluated in AA patients. Methods: Alopecia areata patients with and without concomitant atopic dermatitis were randomized 2:1 to receive weekly subcutaneous dupilumab (300 mg) or placebo for 24 weeks, followed by another 24‐week dupilumab open‐label phase. The primary outcome was change from baseline in the Severity of Alopecia Tool (SALT) score at week 24; secondary outcomes included a range of measures of hair regrowth. Results: Forty and 20 patients were assigned to the dupilumab and placebo arms, respectively. At week 24, disease worsening was documented in the placebo arm, with a least‐squares mean change in the SALT score of −6.5 (95% confidence‐interval [CI], −10.4 to −2.6), versus a change of 2.2 (95% CI, −0.6 to 4.94) in the dupilumab arm (p <.05). After 48 weeks of dupilumab treatment, 32.5%, 22.5% and 15% of patients achieved SALT30/SALT50/SALT75 improvement, respectively, while in patients with baseline IgE ≥ 200 IU/ml response rates increased to 53.8%, 46.2%, and 38.5%, respectively. Moreover, baseline IgE predicts treatment response with 83% accuracy. No new safety signals were detected. Conclusions: This hypothesis‐driven trial is the first to indicate the possible pathogenic role of the Th2 axis and Th2 targeting in AA patients. Patient selection based on baseline serum IgE levels may improve treatment results (Clinicaltrials.gov number, NCT03359356). [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common inflammatory skin disease associated with barrier disfunction and T SB H sb 2/T SB H sb 22 immune polarity.1,2 Patients with AD are often colonized or infected with I Staphylococcus aureus i ( I S. aureus i ).3 Recent large cohort studies and skin microbiome analyses have identified that AD is dominated by I S. aureus i .4 However, the interaction of cytokines and bacteria in AD skin remains unclear. Keywords: atopic dermatitis; dermatology; infections; inflammation; innate immunity; keratinocytes EN atopic dermatitis dermatology infections inflammation innate immunity keratinocytes 3534 3537 4 11/01/21 20211101 NES 211101 ACKNOWLEDGEMENTS KY was supported by Japan Society for the Promotion of Science (JSPS) overseas research fellowships from 2020 to 2022. TH2 cytokines and Staphylococcus aureus cooperatively induce atopic dermatitis-like transcriptomes. [Extracted from the article]

SARS-CoV-2 receptor ACE2 protein expression in serum is significantly associated with age A trend toward significantly greater ACE2 expression was observed in healthy African American adults versus healthy European American adults, as well as in European American AD infants/toddlers versus both Asian and African American AD infants/toddlers ( I P i < .1; Figure S1C). [Extracted from the article]

Background: Skin biopsies promote our understanding of atopic dermatitis/AD pathomechanisms in infants/toddlers with early‐onset AD, but are not feasible in pediatric populations. Tape strips are an emerging, minimally invasive alternative, but global transcriptomic profiling in early pediatric AD is lacking. We aimed to provide global lesional and nonlesional skin profiles of infants/toddlers with recent‐onset, moderate‐to‐severe AD using tape strips. Methods: Sixteen tape strips were collected for RNA‐seq profiling from 19 infants/toddlers (<5 years old; lesional and nonlesional) with early‐onset moderate‐to‐severe AD (≤6 months) and 17 healthy controls. Results: We identified 1829 differentially expressed genes/DEGs in lesional AD and 662 DEGs in nonlesional AD, vs healthy skin (fold‐change ≥2, FDR <0.05), with 100% sample recovery. Both lesional and nonlesional skin showed significant dysregulations of Th2 (CCL17 and IL4R) and Th22/Th17 (IL36G, CCL20, and S100As)‐related genes, largely lacking significant Th1‐skewing. Significant down‐regulation of terminal differentiation (FLG and FLG2), lipid synthesis/metabolism (ELOVL3 and FA2H), and tight junction (CLDN8) genes were primarily seen in lesional AD. Significant negative correlations were identified between Th2 measures and epidermal barrier gene‐subsets and individual genes (FLG with IL‐4R and CCL17; r < −0.4, P <.05). Significant correlations were also identified between clinical measures (body surface area/BSA, pruritus ADQ, and transepidermal water loss/TEWL) with immune and barrier mRNAs in lesional and/or nonlesional AD (FLG/FLG2 with TEWL; r < −0.4, P <.05). Conclusion: RNA‐seq profiling using tape strips in early‐onset pediatric AD captures immune and barrier alterations in both lesional and nonlesional skin. Tape strips provide insight into disease pathomechanisms and cutaneous disease activity. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusions While B‐cells have historically been implicated in allergy development, a growing body of evidence supports their role in atopic dermatitis (AD). B‐cell differentiation across ages in AD, and its relation to disease severity scores, has not been well defined.To compare the frequency of B‐cell subsets in blood of 0–5, 6–11, 12–17, and ≥18 years old patients with AD versus age‐matched controls.Flow cytometry was used to measure B‐cell subset frequencies in the blood of 27 infants, 17 children, 11 adolescents, and 31 adults with moderate‐to‐severe AD and age‐matched controls. IgD/CD27 and CD24/CD38 core gating systems and an 11‐color flow cytometry panel were used to determine frequencies of circulating B‐cell subsets. Serum total and allergen‐specific IgE (sIgEs) levels were measured using ImmunoCAP®.Adolescents with AD had lower frequencies of major B‐cells subsets (p < .03). CD23 expression increased with age and was higher in AD compared to controls across all age groups (p < .04). In AD patients, multiple positive correlations were observed between IL‐17‐producing T‐cells and B‐cell subsets, most significantly non‐switched memory (NSM) B‐cells (r = .41, p = .0005). AD severity positively correlated with a list of B‐cell subsets (p < .05). IL‐9 levels gradually increased during childhood, reaching a peak in adolescence, paralleling allergen sensitization, particularly in severe AD. Principal component analysis of the aggregated environmental sIgE data showed that while controls across all ages tightly clustered together, adolescents with AD demonstrated distinct clustering patterns relative to controls.Multiple correlations between B‐cells and T‐cells, as well as disease severity measures, suggest a complex interplay of immune pathways in AD. Unique B‐cell signature during adolescence, with concurrent allergen sensitization and IL‐9 surge, point to a potentially wider window of opportunity to implement interventions that may prevent the progression of the atopic march. [ABSTRACT FROM AUTHOR]