Journal ArticleDOI
Intraindividual genome expression analysis reveals a specific molecular signature of psoriasis and eczema
Maria Quaranta,Bettina Knapp,Natalie Garzorz,M. Mattii,Venu Pullabhatla,Davide Pennino,Christian Andres,Claudia Traidl-Hoffmann,Andrea Cavani,Fabian J. Theis,Johannes Ring,Carsten B. Schmidt-Weber,Stefanie Eyerich,Kilian Eyerich +13 more
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TLDR
It is found that psoriasis-specific genes involved not only immune mediators but also regulators of metabolism and eczema-related genes included those related to the epidermal barrier and inflammasome activation.Abstract:
Previous attempts to gain insight into the pathogenesis of psoriasis and eczema by comparing their molecular signatures were hampered by the high interindividual variability of those complex diseases. In patients affected by both psoriasis and nonatopic or atopic eczema simultaneously (n = 24), an intraindividual comparison of the molecular signatures of psoriasis and eczema identified genes and signaling pathways regulated in common and exclusive for each disease across all patients. Psoriasis-specific genes were important regulators of glucose and lipid metabolism, epidermal differentiation, as well as immune mediators of T helper 17 (TH17) responses, interleukin-10 (IL-10) family cytokines, and IL-36. Genes in eczema related to epidermal barrier, reduced innate immunity, increased IL-6, and a TH2 signature. Within eczema subtypes, a mutually exclusive regulation of epidermal differentiation genes was observed. Furthermore, only contact eczema was driven by inflammasome activation, apoptosis, and cellular adhesion. On the basis of this comprehensive picture of the pathogenesis of psoriasis and eczema, a disease classifier consisting of NOS2 and CCL27 was created. In an independent cohort of eczema (n = 28) and psoriasis patients (n = 25), respectively, this classifier diagnosed all patients correctly and also identified initially misdiagnosed or clinically undifferentiated patients.read more
Citations
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Journal ArticleDOI
Psoriasis pathogenesis and the development of novel targeted immune therapies
TL;DR: Clinical trial data for mAbs against IL‐17 signaling and newer IL‐23p19 antagonists underscore the central role of these cytokines as predominant drivers of psoriatic disease.
Journal ArticleDOI
Cellular and molecular immunologic mechanisms in patients with atopic dermatitis
Thomas Werfel,Jean-Pierre Allam,Tilo Biedermann,Kilian Eyerich,Stefanie Gilles,Emma Guttman-Yassky,Wolfram Hoetzenecker,Edward F. Knol,Hans-Uwe Simon,Andreas Wollenberg,Thomas Bieber,Roger Lauener,Peter Schmid-Grendelmeier,Claudia Traidl-Hoffmann,Cezmi A. Akdis +14 more
TL;DR: Best evidence of the clinical efficacy of novel immunologic approaches using biological agents in patients with AD is available for the anti-IL-4 receptor α-chain antibody dupilumab, but a number of studies are currently ongoing with other specific antagonists to immune system players.
Journal ArticleDOI
The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization.
Shinji Noda,Mayte Suárez-Fariñas,Benjamin Ungar,Benjamin Ungar,Soo Jung Kim,Cristina de Guzman Strong,Hui Xu,Xiangyu Peng,Yeriel Estrada,Saeko Nakajima,Tetsuya Honda,Jung U Shin,Hemin Lee,James G. Krueger,Kwang Hoon Lee,Kenji Kabashima,Emma Guttman-Yassky,Emma Guttman-Yassky +17 more
TL;DR: The Asian AD phenotype presents (even in the presence of increased IgE levels) a blended phenotype between that of EA patients with AD and those with psoriasis, including increased hyperplasia, parakeratosis, higher TH17 activation, and a strong TH2 component.
Journal ArticleDOI
The immunogenetics of Psoriasis: A comprehensive review.
TL;DR: Novel genetic findings involve immune genes with less clear roles in psoriasis pathogenesis that open opportunities to explore novel therapeutic targets and potentially the development of personalized medicine, as well as discover new biology of human skin disease.
Journal ArticleDOI
Atopic Dermatitis Is an IL-13–Dominant Disease with Greater Molecular Heterogeneity Compared to Psoriasis
Lam C. Tsoi,Elke Rodriguez,Frauke Degenhardt,Hansjörg Baurecht,Ulrike Wehkamp,Natalie Volks,Silke Szymczak,William R. Swindell,Mrinal K. Sarkar,Kalpana Raja,Shuai Shao,Matthew Patrick,Yilin Gao,Ranjitha Uppala,Bethany E. Perez White,Spiro Getsios,Paul W. Harms,Emanual Michael Maverakis,James T. Elder,James T. Elder,Andre Franke,Johann E. Gudjonsson,Stephan Weidinger +22 more
TL;DR: This study is by far the largest study comparing the AD and psoriasis transcriptomes using RNA sequencing and demonstrating the shared inflammatory components, as well as specific discordant cytokine signatures of these two skin diseases.
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