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

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Cyclosporine in patients with atopic dermatitis modulates activated inflammatory pathways and reverses epidermal pathology Saakshi Khattri, MD, Avner Shemer, MD, Mariya Rozenblit, BA, Nikhil Dhingra, BS, Tali Czarnowicki, MD, Robert Finney, MD, Patricia Gilleaudeau, NP, Mary Sullivan-Whalen, NP, Xiuzhong Zheng, MSc, Hui Xu, MSc, Irma Cardinale, MSc, Cristina de Guzman Strong, PhD, Juana Gonzalez, PhD, Mayte Suárez-Fariñas, PhD, Jim G. Krueger, MD, PhD, Emma Guttman-Yassky, MD, PhD Journal of Allergy and Clinical Immunology Volume 133, Issue 6, Pages 1626-1634 (June 2014) DOI: 10.1016/j.jaci.2014.03.003 Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Representative staining with hematoxylin and eosin (HE; A) and the proliferation marker K16 (B). All 19 lesional (LS) samples were K16 positive at week 0, and only 2 of 19 lesional samples retained positivity at week 12. Significant decreases in epidermal thickness (C), Ki67+ cell counts (D), and K16 mRNA expression (E) with CsA were shown. Values are presented as means ± SDs (Fig 1, C and D) or means ± SEMs (Fig 1, E). ***P < .001, posttreatment versus pretreatment. Journal of Allergy and Clinical Immunology 2014 133, 1626-1634DOI: (10.1016/j.jaci.2014.03.003) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Genomic differences in patients with AD before and after CsA treatment. Significant changes in differentially expressed genes defining the AD transcriptome (A) occur by week 2 in nonlesional (NL) and lesional (LS) skin (B). Heat maps are arranged by patient SCORAD scores (white-to-black gradient). Pink indicates patients with unknown SCORAD scores. Red indicates upregulated and blue indicates downregulated values. Journal of Allergy and Clinical Immunology 2014 133, 1626-1634DOI: (10.1016/j.jaci.2014.03.003) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Significant downregulation of inflammatory markers after CsA in AD skin, as quantified by using real-time PCR. A-X, Posttreatment versus pretreatment mRNA expression differences (FCHs) of selected genes, as grouped by the inflammatory pathway, in lesional and nonlesional AD skin at weeks 2 and 12 of treatment. Values are presented as means ± SEMs with posttreatment versus pretreatment P values. See Table E4 for CIs. Journal of Allergy and Clinical Immunology 2014 133, 1626-1634DOI: (10.1016/j.jaci.2014.03.003) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 A summary heat map of mRNA changes (real-time PCR) in weeks 2 and 12 lesional and nonlesional skin with FCHs (blue and red). *P < .05 and **P < .01, posttreatment versus pretreatment. Journal of Allergy and Clinical Immunology 2014 133, 1626-1634DOI: (10.1016/j.jaci.2014.03.003) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Journal of Allergy and Clinical Immunology 2014 133, 1626-1634DOI: (10.1016/j.jaci.2014.03.003) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Journal of Allergy and Clinical Immunology 2014 133, 1626-1634DOI: (10.1016/j.jaci.2014.03.003) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Journal of Allergy and Clinical Immunology 2014 133, 1626-1634DOI: (10.1016/j.jaci.2014.03.003) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E4 Journal of Allergy and Clinical Immunology 2014 133, 1626-1634DOI: (10.1016/j.jaci.2014.03.003) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E5 Journal of Allergy and Clinical Immunology 2014 133, 1626-1634DOI: (10.1016/j.jaci.2014.03.003) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E6 Journal of Allergy and Clinical Immunology 2014 133, 1626-1634DOI: (10.1016/j.jaci.2014.03.003) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E7 Journal of Allergy and Clinical Immunology 2014 133, 1626-1634DOI: (10.1016/j.jaci.2014.03.003) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E8 Journal of Allergy and Clinical Immunology 2014 133, 1626-1634DOI: (10.1016/j.jaci.2014.03.003) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions