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 Maverakis, James T Elder, Andre Franke, Johann E Gudjonsson, Stephan Weidinger
Author Information
Lam C Tsoi: Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA; Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
Elke Rodriguez: Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Kiel, Germany.
Frauke Degenhardt: Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Kiel, Germany.
Hansjörg Baurecht: Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Kiel, Germany.
Ulrike Wehkamp: Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Kiel, Germany.
Natalie Volks: Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Kiel, Germany.
Silke Szymczak: Institute of Medical Informatics and Statistics, Kiel University, Kiel, Germany.
William R Swindell: Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA.
Mrinal K Sarkar: Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Kalpana Raja: Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Shuai Shao: Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Matthew Patrick: Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Yilin Gao: Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA.
Ranjitha Uppala: Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Bethany E Perez White: Department of Dermatology, Northwestern University, Chicago, Illinois, USA.
Spiro Getsios: Department of Dermatology, Northwestern University, Chicago, Illinois, USA.
Paul W Harms: Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Emanual Maverakis: Department of Dermatology, School of Medicine, UC Davis Medical Center, Sacramento, California, USA.
James T Elder: Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA; Ann Arbor Veterans Affairs Hospital, Ann Arbor, Michigan, USA.
Andre Franke: Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Kiel, Germany.
Johann E Gudjonsson: Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA. Electronic address: johanng@med.umich.edu.
Stephan Weidinger: Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Kiel, Germany.
Atopic dermatitis (AD) affects up to 20% of children and adults worldwide. To gain a deeper understanding of the pathophysiology of AD, we conducted a large-scale transcriptomic study of AD with deeply sequenced RNA-sequencing samples using long (126-bp) paired-end reads. In addition to the comparisons against previous transcriptomic studies, we conducted in-depth analysis to obtain a high-resolution view of the global architecture of the AD transcriptome and contrasted it with that of psoriasis from the same cohort. By using 147 RNA samples in total, we found striking correlation between dysregulated genes in lesional psoriasis and lesional AD skin with 81% of AD dysregulated genes being shared with psoriasis. However, we described disease-specific molecular and cellular features, with AD skin showing dominance of IL-13 pathways, but with near undetectable IL-4 expression. We also demonstrated greater disease heterogeneity and larger proportion of dysregulated long noncoding RNAs in AD, and illustrated the translational impact, including skin-type classification and drug-target prediction. 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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