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,

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Presentation transcript:

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, Hitokazu Esaki, MD, Margeaux Oliva, BA, Thy Nhat Huynh, MD, Benjamin Ungar, BA, Norma Kunjravia, MD, Rivka Friedland, MD, Xiangyu Peng, MSc, Xiuzhong Zheng, MSc, Yeriel D. Estrada, BSc, James G. Krueger, MD, PhD, Keith A. Choate, Mayte Suárez-Fariñas, PhD, Emma Guttman-Yassky, MD, PhD Journal of Allergy and Clinical Immunology Volume 139, Issue 1, Pages 152-165 (January 2017) DOI: 10.1016/j.jaci.2016.07.019 Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 A-E, Representative staining in patients with ichthyoses, AD, or psoriasis (PSO) and control subjects by using hematoxylin and eosin (Fig 1, A), K16 with fractions of positive samples (Fig 1, B), CD3+ T cells (Fig 1, C), CD11c+ DCs (Fig 1, D), and FLG (Fig 1, E). F-J, Quantification of epidermal thickness (Fig 1, F), K16 mRNA (Fig 1, G), CD3+ and CD11c+ cells (Fig 1, H and I), and FLG mRNA (Fig 1, J). mRNA log2 values were adjusted to hARP. Results are presented as means ± SEMs. Control comparisons: *P < .05, **P < .01, and ***P < .001. LS, Lesional; NL, nonlesional. Journal of Allergy and Clinical Immunology 2017 139, 152-165DOI: (10.1016/j.jaci.2016.07.019) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 A-W, Comparison of immune markers in patients with ichthyosis subtypes, AD, or psoriasis (PSO) and control subjects by using RT-PCR. IL-17/TNF-α–synergistic/additive genes are highlighted in green. mRNA log2 values were adjusted to hARP expression levels. Asterisks without bars denote comparison with control subjects. Asterisks above bars denote P values, with comparators defined by the bar. Values are presented as least-square means (log2 expression/hARP) ± SEMs. +P < .1, *P < .05, **P < .01, and ***P < .001. Journal of Allergy and Clinical Immunology 2017 139, 152-165DOI: (10.1016/j.jaci.2016.07.019) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 A, Unsupervised hierarchical clustering of mRNA expression in patients with AD, psoriasis, or ichthyosis and control subjects as a heat map with fold changes between diseased and healthy skin. Green box, Cluster of upregulated IL-17–related genes in patients with ichthyosis and those with psoriasis. +P < .1, *P < .05, and **P < .01. Red, Upregulation; blue, downregulation. B, Unsupervised clustering of samples (phylogenetic tree) based on expression profiles of 45 immune/barrier markers. Distance, Pearson correlation; agglomeration, average. LS, Lesional. Journal of Allergy and Clinical Immunology 2017 139, 152-165DOI: (10.1016/j.jaci.2016.07.019) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Representative IHC staining of IL-17 induced antimicrobials in patients with ichthyoses, AD, or psoriasis (PSO) and control subjects by using CCL20 (A), LCN2 (B), and DEFB4 (C), showing strong protein expression in the skin of patients with ichthyoses similar to what is seen in the skin of patients with psoriasis. Journal of Allergy and Clinical Immunology 2017 139, 152-165DOI: (10.1016/j.jaci.2016.07.019) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Pearson correlation plots of mRNA gene expression that correlated highest with overall clinical severity scores (IASI; A), erythema severity subscores (IASI-E; B), and TEWL (C) in patients with ichthyosis subtypes. r, Pearson correlation coefficient with associated P value; y, equation for linear regression (blue line) with its CI (smoothed CI in gray). Journal of Allergy and Clinical Immunology 2017 139, 152-165DOI: (10.1016/j.jaci.2016.07.019) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 6 Correlation matrix of all ichthyosis measurements. A, Unsupervised hierarchical clustering of clinical scores (blue) with barrier/immune markers (black), including IL-17–synergistic/additive genes (green). Distance, Pearson correlation; algorithm, McQuitty agglomeration. B, Correlation heat map. Pink box, Correlations with IASI score. Brown box, Most significant cluster of IL-17– synergistic/additive genes, with the green box highlighting the IASI-E subcluster. Gray box, Pruritus correlations. red, Positive correlations; blue, negative correlations. *P < .05, **P < .01, and ***P < .001. Journal of Allergy and Clinical Immunology 2017 139, 152-165DOI: (10.1016/j.jaci.2016.07.019) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions