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

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Presentation transcript:

Intrinsic atopic dermatitis shows similar TH2 and higher TH17 immune activation compared with extrinsic atopic dermatitis Mayte Suárez-Fariñas, PhD, Nikhil Dhingra, BS, Julia Gittler, BA, Avner Shemer, MD, Irma Cardinale, MSc, Cristina de Guzman Strong, PhD, James G. Krueger, MD, PhD, Emma Guttman-Yassky, MD, PhD Journal of Allergy and Clinical Immunology Volume 132, Issue 2, Pages 361-370 (August 2013) DOI: 10.1016/j.jaci.2013.04.046 Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Scatter plot of the correlation between IgE levels and SCORAD scores in extrinsic (red) and intrinsic (blue) AD categories. Lines represent linear regression within each group. Only patients with extrinsic AD exhibit a significant Pearson correlation between SCORAD scores and IgE levels (R = 0.76, P = 3.7 × 10−7), which is lacking in patients with intrinsic AD (R = 0.11, P = .77). Journal of Allergy and Clinical Immunology 2013 132, 361-370DOI: (10.1016/j.jaci.2013.04.046) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Representative hematoxylin and eosin (H&E) staining and IHC of lesional and nonlesional skin of patients with extrinsic and those with intrinsic AD. A, H&E staining demonstrates similar hyperplasia in extrinsic and intrinsic lesions. B-F, Large T-cell (CD3+), myeloid DC (CD11c+), mature DC (CD83+), inflammatory DC (FCεRI+), and atopic DC (OX40L+) infiltrates are evident in lesional skin of both groups (original magnification ×10). AL, Lesional; ANL, nonlesional. Journal of Allergy and Clinical Immunology 2013 132, 361-370DOI: (10.1016/j.jaci.2013.04.046) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Bar plots of cell counts (IHC) in patients with lesional and nonlesional intrinsic and extrinsic AD skin. A and B, Similar epidermal hyperplasia (thickness, Ki67+). C-L, Both variants showed significant increases (greatest in intrinsic patients) in T cells (CD3+ and CD8+), various DCs, and Langerhans cells (CD11c+, CD1a+, CD83+, CD1c+, FcεRI+, TRAIL+, and OX40L+) in lesional versus nonlesional skin. M-O, Neutrophil (NE) counts were more increased in intrinsic lesions; extrinsic lesions exhibited greater eosinophil counts (major basic protein [MBP]+) and plasmacytoid DCs (blood dendritic cell antigen 2 [BDCA2]+). Degree of significance between any comparisons is indicated if the P value is less than .1. Asterisks in parentheses (top right corners) represent significance of the interaction term of the ANOVA model; if present, the AD phenotypes greatly differ between the variants (means ± SEMs). *P < .10, **P < .05, ***P < .01, and ****P < .001. AL, Lesional; ANL, nonlesional. Journal of Allergy and Clinical Immunology 2013 132, 361-370DOI: (10.1016/j.jaci.2013.04.046) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Bar plots of mRNA expression in lesional and nonlesional skin from patients with intrinsic and those with extrinsic AD. A-DD, Similar hyperplasia and activation of all inflammatory axes characterize lesional versus nonlesional skin in both variants. Intrinsic lesions exhibited more significant increases in markers of inflammation and TH1, TH22, TH17, and regulatory T (Treg) cells. Degree of significance between any comparisons is indicated if the P value is less than .1. Asterisks in parentheses (top right corners) represent significance of the interaction term of the ANOVA model; if present, the AD phenotypes greatly differ between the variants (means ± SEMs). *P < .10, **P < .05, ***P < .01, and ****P < .001. AL, Lesional; ANL, nonlesional. Journal of Allergy and Clinical Immunology 2013 132, 361-370DOI: (10.1016/j.jaci.2013.04.046) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Word clouds representing the AD phenotypes, as determined by lesional and nonlesional differences (by using IHC and RT-PCR) for intrinsic (A and D) and extrinsic (B and E) AD. Word sizes are proportional to fold change (FCH) differences, which are scaled relative to the numbers in black. Significance and upregulation/downregulation indicated by color (see key). Scatter plots compare extrinsic and intrinsic phenotypes in IHC (C) and RT-PCR (F). Circle diameter represents relative differences, and darker colors represent increased significance. Journal of Allergy and Clinical Immunology 2013 132, 361-370DOI: (10.1016/j.jaci.2013.04.046) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 6 Word clouds representing correlations between cellular and molecular markers (IHC and RT-PCR) and disease severity (SCORAD score) in lesional intrinsic (A) and extrinsic (B) AD. Words in the clouds are proportional to the correlation coefficient between markers and SCORAD scores and color coded for significance and upregulation/downregulation (see key). A perfect correlation is indicated by 1 (black). Journal of Allergy and Clinical Immunology 2013 132, 361-370DOI: (10.1016/j.jaci.2013.04.046) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Journal of Allergy and Clinical Immunology 2013 132, 361-370DOI: (10.1016/j.jaci.2013.04.046) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Journal of Allergy and Clinical Immunology 2013 132, 361-370DOI: (10.1016/j.jaci.2013.04.046) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Journal of Allergy and Clinical Immunology 2013 132, 361-370DOI: (10.1016/j.jaci.2013.04.046) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions