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

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Presentation on theme: "Comparative transcriptomic analyses of atopic dermatitis and psoriasis reveal shared neutrophilic inflammation  David F. Choy, BS, Daniel K. Hsu, PhD,"— Presentation transcript:

1 Comparative transcriptomic analyses of atopic dermatitis and psoriasis reveal shared neutrophilic inflammation  David F. Choy, BS, Daniel K. Hsu, PhD, Dhaya Seshasayee, PhD, Maxwell A. Fung, MD, Zora Modrusan, PhD, Flavius Martin, MD, Fu- Tong Liu, MD, PhD, Joseph R. Arron, MD, PhD  Journal of Allergy and Clinical Immunology  Volume 130, Issue 6, Pages e5 (December 2012) DOI: /j.jaci Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 Comparative expression analysis of CCGfs defines GSs. T-statistics of within-disease lesional versus nonlesion comparisons are depicted by using scatter plots. The AD-GS (red symbols) and Ps–GS (blue symbols) comprise unique and opposing differentially expressed genes (purple symbols). Commonly and not differentially expressed (NOT DE) genes are represented by green and gray symbols, respectively. Journal of Allergy and Clinical Immunology  , e5DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 AD-GS. A, Genes comprising AD-GS are represented by an expression heat map and organized by PCA factors. Columns (samples) are arranged by PC1 score. Rows (genes) are organized by PC1 loadings. B-D, PC1 significantly correlates with serum IgE levels (Fig 2, B), blood eosinophil counts (Fig 2, C), and biopsy specimen eosinophil counts (Fig 2, D). Journal of Allergy and Clinical Immunology  , e5DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Ps-GS expression. Summary statistics (−log10 FDRs and fold-change direction) of moderated paired t tests of lesional psoriasis versus nonlesional psoriasis is plotted by using an annotated strip chart for all 217 CCGfs. Genes of the Ps-GS, which are all differentially expressed with FDRs of less than 0.05, are annotated. Journal of Allergy and Clinical Immunology  , e5DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 C-GS expression signature correlates with blood neutrophil counts. A, Genes comprising the C-GS are represented by using an expression heat map and organized by PCA factors. Columns (samples) are arranged by PC1 score. Rows (genes) are organized by PC1 loading. Missing expression values are represented in white. B, PC1 significantly correlates with blood neutrophil counts. Ps, Psoriasis. Journal of Allergy and Clinical Immunology  , e5DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 C-GS expression signature correlates with neutrophil enumeration by histology. A, Detection of neutrophil elastase-2, lipocalin-2, and MPO by means of immunohistochemistry and H&E in representative AD lesional skin without excoriations from different subjects. B, Cell counts for lesions from patients with AD and those with psoriasis (Ps). C, Scatter plot matrix of biopsy neutrophil indicators and C-GS PC1 scores (P < .05, all pairwise comparisons). Journal of Allergy and Clinical Immunology  , e5DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig E1 Representative lesion profiles. A, Representative AD skin lesion biopsied. B, Representative histology of AD. Most AD biopsy specimens in this study contained focal crust, with none more prominent than the degree depicted here. Scale bar = 50 μm. C, Histology of psoriasis. Occasional cases exhibited prominent crust. Scale bar = 50 μm. Journal of Allergy and Clinical Immunology  , e5DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 Fig E2 Chemokine (C-C motif) ligand 26 (CCL26) expression. CCL26 is an opposing dysregulated (FDR < 0.05) CCGf gene in patients with lesional AD and those with psoriasis (Ps). Subject-matched nonlesional (nL) and lesional (L) sample expression values are linked by line segments. Journal of Allergy and Clinical Immunology  , e5DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

9 Fig E3 Lesion, diagnosis, and subject ID are important sources of CCGf expression variation. PCA demonstrates that lesion and diagnosis are informative sources of CCGf expression variation. Patient-matched nonlesional and lesional samples are connected by arrows. Ps, Psoriasis. Journal of Allergy and Clinical Immunology  , e5DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

10 Fig E4 C-GS signature score. C-GS expression was summarized by using SPCA (see the Methods section). C-GS is represented by box plots and points. Statistics were calculated by using the pairwise Wilcoxon test, and significance is expressed as the FDR. AD-L, AD lesion; Ps-L, psoriatic lesion. Journal of Allergy and Clinical Immunology  , e5DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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