Minimally invasive skin tape strip RNA sequencing identifies novel characteristics of the type 2–high atopic dermatitis disease endotype Nathan Dyjack,

Slides:

Advertisements

Similar presentations

MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers Thomas X. Lu,

Advertisements

Anti–IL-23A mAb BI for treatment of moderate-to-severe psoriasis: Safety, efficacy, pharmacokinetics, and biomarker results of a single-rising-dose,

Targeted deep sequencing identifies rare loss-of-function variants in IFNGR1 for risk of atopic dermatitis complicated by eczema herpeticum Li Gao, MD,

Petrolatum: Barrier repair and antimicrobial responses underlying this “inert” moisturizer Tali Czarnowicki, MD, Dana Malajian, BA, Saakshi Khattri, MD,

Cyclosporine in patients with atopic dermatitis modulates activated inflammatory pathways and reverses epidermal pathology Saakshi Khattri, MD, Avner.

Natalija Novak, MD Journal of Allergy and Clinical Immunology

Flow cytometry imaging identifies rare TH2 cells expressing thymic stromal lymphopoietin receptor in a “proallergic” milieu Amanda J. Reefer, MS, Kathryn.

Induced sputum proteome in healthy subjects and asthmatic patients

RNA sequencing atopic dermatitis transcriptome profiling provides insights into novel disease mechanisms with potential therapeutic implications Mayte.

Asthma inflammatory phenotypes show differential microRNA expression in sputum Tania Maes, PhD, Francisco Avila Cobos, MSc, Florence Schleich, MD, PhD,

An IL-17–dominant immune profile is shared across the major orphan forms of ichthyosis Amy S. Paller, MD, MS, Yael Renert-Yuval, MD, Maria Suprun, MPH,

Ryan H. Dougherty, MD, Sukhvinder S

Transcriptome Analysis of Psoriasis in a Large Case–Control Sample: RNA-Seq Provides Insights into Disease Mechanisms Bingshan Li, Lam C. Tsoi, William.

Intrinsic atopic dermatitis shows similar TH2 and higher TH17 immune activation compared with extrinsic atopic dermatitis Mayte Suárez-Fariñas, PhD,

Atopic dermatitis: Age and race do matter!

Epithelial proteome profiling suggests the essential role of interferon-inducible proteins in patients with allergic rhinitis Joseph Ndika, PhD, Liisa.

MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers Thomas X. Lu,

Histologic eosinophilic gastritis is a systemic disorder associated with blood and extragastric eosinophilia, TH2 immunity, and a unique gastric transcriptome

Identification of novel gene signatures in patients with atopic dermatitis complicated by eczema herpeticum Lianghua Bin, MD, PhD, Michael G. Edwards,

Inflammatory marker analysis in psoriatic skin under topical phosphodiesterase 4 inhibitor treatment Lennart M. Roesner, PhD, Petra Kienlin, Gabriele.

Dupilumab improves the molecular signature in skin of patients with moderate-to-severe atopic dermatitis Jennifer D. Hamilton, PhD, Mayte Suárez-Fariñas,

Progressive activation of TH2/TH22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis Julia K. Gittler, BA,

MicroRNA activation signature in patients with hemophagocytic lymphohistiocytosis and reversibility with disease-specific therapy Janos Sumegi, MD, PhD,

Defective killing of Staphylococcus aureus in atopic dermatitis is associated with reduced mobilization of human β-defensin-3 Kevin O. Kisich, PhD, Charles.

Dissecting childhood asthma with nasal transcriptomics distinguishes subphenotypes of disease Alex Poole, MS, Cydney Urbanek, BS, Celeste Eng, BS, Jeoffrey.

Anti–IL-23A mAb BI for treatment of moderate-to-severe psoriasis: Safety, efficacy, pharmacokinetics, and biomarker results of a single-rising-dose,

Therapeutic pipeline for atopic dermatitis: End of the drought?

Differential control of TH1 versus TH2 cell responses by the combination of low-dose steroids with β2-adrenergic agonists Elena Goleva, PhD, Annegret.

Relations between epidermal barrier dysregulation and Staphylococcus species– dominated microbiome dysbiosis in patients with atopic dermatitis Can Altunbulakli,

IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis James G. Krueger, MD, Scott Fretzin, MD, Mayte Suárez-Fariñas,

Specificity protein 1 is pivotal in the skin’s antiviral response

Reversal of atopic dermatitis with narrow-band UVB phototherapy and biomarkers for therapeutic response Suzanne Tintle, BS, Avner Shemer, MD, Mayte Suárez-Fariñas,

Severe atopic dermatitis is characterized by selective expansion of circulating TH2/TC2 and TH22/TC22, but not TH17/TC17, cells within the skin-homing.

Major differences between human atopic dermatitis and murine models, as determined by using global transcriptomic profiling David A. Ewald, MSc, Shinji.

Identification of TNF-related apoptosis-inducing ligand and other molecules that distinguish inflammatory from resident dendritic cells in patients with.

Distinct behavior of human Langerhans cells and inflammatory dendritic epidermal cells at tight junctions in patients with atopic dermatitis Kazue Yoshida,

Ζ Chain–associated protein of 70 kDa (ZAP70) deficiency in human subjects is associated with abnormalities of thymic stromal cells: Implications for T-cell.

Alopecia areata profiling shows TH1, TH2, and IL-23 cytokine activation without parallel TH17/TH22 skewing Mayte Suárez-Fariñas, PhD, Benjamin Ungar,

Serum from Asian patients with atopic dermatitis is characterized by TH2/TH22 activation, which is highly correlated with nonlesional skin measures Huei-Chi.

Small RNA profiling reveals deregulated phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/Akt pathway in bronchial smooth muscle.

Comparative transcriptomic analyses of atopic dermatitis and psoriasis reveal shared neutrophilic inflammation David F. Choy, BS, Daniel K. Hsu, PhD,

Suction blistering the lesional skin of vitiligo patients reveals useful biomarkers of disease activity James P. Strassner, BS, Mehdi Rashighi, MD, Maggi.

Programmed cell death ligand 1 alleviates psoriatic inflammation by suppressing IL-17A production from programmed cell death 1–high T cells Jong Hoon.

An integrated model of alopecia areata biomarkers highlights both TH1 and TH2 upregulation Teresa Song, BS, Ana B. Pavel, PhD, Huei-Chi Wen, MD, PhD,

Corticosteroid-resistant asthma is associated with classical antimicrobial activation of airway macrophages Elena Goleva, PhD, Pia J. Hauk, MD, Clifton.

Anti–IL-23A mAb BI for treatment of moderate-to-severe psoriasis: Safety, efficacy, pharmacokinetics, and biomarker results of a single-rising-dose,

Profiling of human CD4+ T-cell subsets identifies the TH2-specific noncoding RNA GATA3-AS1 Huan Zhang, MD, PhD, Colm E. Nestor, PhD, Shuli Zhao, PhD,

An algorithm for the classification of mRNA patterns in eosinophilic esophagitis: Integration of machine learning Benjamin F. Sallis, BS, Lena Erkert,

The signal transducer and activator of transcription 6 gene (STAT6) increases the propensity of patients with atopic dermatitis toward disseminated viral.

Major differences in inflammatory dendritic cells and their products distinguish atopic dermatitis from psoriasis Emma Guttman-Yassky, MD, MSc, Michelle.

Thymic stromal lymphopoietin–activated invariant natural killer T cells trigger an innate allergic immune response in atopic dermatitis Wen Hao Wu, PhD,

Macrophage polarization: Reaching across the aisle?

Dupilumab improves the molecular signature in skin of patients with moderate-to-severe atopic dermatitis Jennifer D. Hamilton, PhD, Mayte Suárez-Fariñas,

CC chemokine receptors CCR1 and CCR4 are expressed on airway mast cells in allergic asthma Kawa Amin, PhD, Christer Janson, MD, PhD, Ilkka Harvima, MD,

Assessment of clinical findings, tryptase levels, and bone marrow histopathology in the management of pediatric mastocytosis Melody C. Carter, MD, Sarah.

Attenuated neutrophil axis in atopic dermatitis compared to psoriasis reflects TH17 pathway differences between these diseases Nikhil Dhingra, BS, Mayte.

Petrolatum: Barrier repair and antimicrobial responses underlying this “inert” moisturizer Tali Czarnowicki, MD, Dana Malajian, BA, Saakshi Khattri, MD,

Sara Paveglio, PhD, MS, Erin Bennett, MS, Kelly L. Hawley, PhD, Adam P

The Editors' Choice Journal of Allergy and Clinical Immunology

Baochen Shi, PhD, Nathanael J

Staphylococcus aureus α-toxin modulates skin host response to viral infection Lianghua Bin, PhD, Byung Eui Kim, MD, Anne Brauweiler, PhD, Elena Goleva,

Does “autoreactivity” play a role in atopic dermatitis?

DLX3-Dependent STAT3 Signaling in Keratinocytes Regulates Skin Immune Homeostasis Shreya Bhattacharya, Jin-Chul Kim, Youichi Ogawa, Gaku Nakato, Veronica.

Expression of chemokines and chemokine receptors in lesional and nonlesional upper skin of patients with atopic dermatitis Eva Gros, MSc, Caroline Bussmann,

Vaccinia virus–specific molecular signature in atopic dermatitis skin

Cytokine modulation of atopic dermatitis filaggrin skin expression

Alex KleinJan, PhD, Monique Willart, BSc, Leonie S

Large-scale gene expression profiling reveals distinct type 2 inflammatory patterns in chronic rhinosinusitis subtypes Matthew A. Tyler, MD, Chris B.

IL-31 is associated with cutaneous lymphocyte antigen–positive skin homing T cells in patients with atopic dermatitis Janine Bilsborough, PhD, Donald.

Immunopathology of atopic dermatitis

Presentation transcript:

Minimally invasive skin tape strip RNA sequencing identifies novel characteristics of the type 2–high atopic dermatitis disease endotype Nathan Dyjack, BA, Elena Goleva, PhD, Cydney Rios, MS, Byung Eui Kim, MD, PhD, Lianghua Bin, MD, PhD, Patricia Taylor, NP, Caroline Bronchick, RN, Clifton F. Hall, MS, Brittany N. Richers, BS, Max A. Seibold, PhD, Donald Y.M. Leung, MD, PhD Journal of Allergy and Clinical Immunology Volume 141, Issue 4, Pages 1298-1309 (April 2018) DOI: 10.1016/j.jaci.2017.10.046 Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Nonlesional AD skin tape strip transcriptomes differ from skin biopsy transcriptomes and better assay the stratum corneum. A, The top 10 expressed genes by tissue type are listed in rank order. B, Multidimensional scaling (MDS) of the top 500 variant genes in nonlesional tape strip, epidermal, and dermal samples separates the samples by tissue. C, The top 10 GO cellular component enrichments in nonlesional tape strip, skin biopsy–separated epidermal, and skin biopsy dermal samples. GO categories highlighted in red were only observed in epidermal and skin tape strip samples. D, Expression of canonical epidermal genes is consistently greatest in skin tape strip samples, next highest in epidermal samples, and lowest in dermal samples. Journal of Allergy and Clinical Immunology 2018 141, 1298-1309DOI: (10.1016/j.jaci.2017.10.046) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Hierarchical clustering of nonlesional skin tape gene expression separates samples from patients with AD from those from healthy control subjects and identifies immune-activated patients with AD. A, Expression heat map and hierarchical clustering of patients with AD and healthy control subjects using nonlesional skin tape expression of genes differentially expressed in patients with AD. B, Expression heat map and hierarchical clustering of the 75 most recurrent leading-edge genes from all immune-related GO categories significantly enriched in patients with AD. A cluster of AD samples (immune activated) is identified that demonstrates distinct upregulation of immune-related genes compared with other patients with AD and healthy control subjects. Journal of Allergy and Clinical Immunology 2018 141, 1298-1309DOI: (10.1016/j.jaci.2017.10.046) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Immune activation signature in patients with AD reflects significant upregulation of type 2 inflammatory genes and the presence of activated TH2 and DCs. A, Ingenuity Pathway Analysis canonical pathway analysis was performed with nonlesional skin tape differentially expressed genes between immune-activated patients with AD and nonactivated patients with AD. The 15 most significantly enriched canonical pathways indicate upregulation of TH2 and DC activity in immune-activated patients with AD. iCOS, Inducible costimulator; iCOSL, inducible costimulator ligand; NFAT, nuclear factor of activated T cells; PKC, protein kinase C. B, Expression of canonical type 2 inflammatory genes is upregulated in skin tape samples of immune-activated patients with AD. C, Graphic display of the canonical Ingenuity Pathway Analysis TH2 pathway showing genes overlaid on an APC and a T cell. Differentially expressed genes are colored by log2 FC. TCR, T-cell receptor. Journal of Allergy and Clinical Immunology 2018 141, 1298-1309DOI: (10.1016/j.jaci.2017.10.046) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 IL-4R protein expression is increased in nonlesional skin of patients with type 2-high AD. Skin biopsy specimens were stained for IL-4R with fluorescent immunohistochemistry. A and B, IL-4R staining in patients with type 2–high (Fig 4, A) and type 2–low (Fig 4, B) AD. IL-4R (Cy3) is shown in red, wheat germ agglutinin (fluorescein isothiocyanate) is shown in green, magnification is ×400, and the bar equals 20 μm. Arrows point to IL-4R–expressing keratinocytes in the epidermis. C, Quantification of IL-4R staining revealed significantly greater IL-4R levels in nonlesional skin of patients with type 2–high than patients with type 2–low AD. Journal of Allergy and Clinical Immunology 2018 141, 1298-1309DOI: (10.1016/j.jaci.2017.10.046) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Nonlesional skin of patients with type 2–high AD is characterized by inflammatory DC signatures. A, Gene expression log2 FCs for DC markers between nonlesional skin of patients with type 2–high versus patients with type 2–low AD is plotted. Gene expression log2 FCs for these DC genes in published IDECs or monocyte-derived DCs versus Langerhans DCs28 and pDCs versus Langerhans DCs.29 B, Immunohistochemistry of skin biopsy specimens reveals numbers of CD207+ (langerin) DCs are greatest in patients with type 2–high AD, followed by patients with type 2–low AD and healthy control subjects. C, CD207 (langerin) staining of skin biopsy specimens from patients with type 2–high AD reveals extension of DC dendrites into the superficial layers of the epidermis. Langerin (Cy3) is shown in red, wheat germ agglutinin (fluorescein isothiocyanate) is shown in green, magnification if ×400, and bar equals 20 μm. Arrows point to langerin-positive cells and dendrites in the upper granular layer of the epidermis. Fluorescein isothiocyanate/Cy3 channels or the Cy3 channel only are shown. D, Genes upregulated in nonlesional skin of patients with type 2–high versus patients with type 2–low AD are plotted by using log2 FCs of differential expressions from IDECs versus Langerhans DCs28 and pDCs versus Langerhans DCs29 generated from published gene expression data. Log2 FCs of type 2–high upregulated genes indicate a skew toward IDECs. Plotted genes were filtered by using a significance threshold of an FDR of less than 0.05. Journal of Allergy and Clinical Immunology 2018 141, 1298-1309DOI: (10.1016/j.jaci.2017.10.046) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 6 Nonlesional skin type 2 inflammatory gene expression patterns are reflective of disease severity and lesional skin expression profiles in patients with AD. A-C, Principal component analysis was performed on nonlesional skin tape strip expression from 656 differentially expressed genes between samples from patients with type 2–high and patients with type 2–low AD. PC2 was strongly correlated (Pearson) with clinical measurements of AD. PC2 positively correlated with EASI score (ρ = 0.616, P = 1.11 × 10−2; Fig 6, A), percentage BSA covered with lesions (ρ = 0.438, P = 1.89 × 10−2; Fig 6, B), and log2 serum IgE level (ρ = 0.705, P = 1.56 × 10−3; Fig 6, C). Type two–low samples are denoted with blue circles, and type 2–high samples are plotted in red circles. D, PC2 values displayed a positive significant trend (by using the Cochran-Armitage trend test) across AD severity levels (P = 5.12 × 10−2). E, The top 250 differentially expressed genes between AD lesional and healthy control tape strips agnostically group nonlesional type 2–high samples with lesional tape strips and type 2–low with healthy control tape strips. Journal of Allergy and Clinical Immunology 2018 141, 1298-1309DOI: (10.1016/j.jaci.2017.10.046) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions