title: Meta-analysis derived atopic dermatitis (MADAD) transcriptome defines a robust AD signature highlighting the involvement of atherosclerosis and lipid metabolism pathways.
abstract: BACKGROUND
  Atopic dermatitis (AD) is a common inflammatory skin disease with limited treatment options. Several microarray experiments have been conducted on lesional/LS and non-lesional/NL AD skin to develop a genomic disease phenotype. Although these experiments have shed light on disease pathology, inter-study comparisons reveal large differences in resulting sets of differentially expressed genes (DEGs), limiting the utility of direct comparisons across studies.
  
  
  METHODS
  We carried out a meta-analysis combining 4 published AD datasets to define a robust disease profile, termed meta-analysis derived AD (MADAD) transcriptome.
  
  
  RESULTS
  This transcriptome enriches key AD pathways more than the individual studies, and associates AD with novel pathways, such as atherosclerosis signaling (IL-37, selectin E/SELE). We identified wide lipid abnormalities and, for the first time in vivo, correlated Th2 immune activation with downregulation of key epidermal lipids (FA2H, FAR2, ELOVL3), emphasizing the role of cytokines on the barrier disruption in AD. Key AD "classifier genes" discriminate lesional from nonlesional skin, and may evaluate therapeutic responses.
  
  
  CONCLUSIONS
  Our meta-analysis provides novel and powerful insights into AD disease pathology, and reinforces the concept of AD as a systemic disease.
authors.affiliation: The Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA. ewald@cbs.dtu.dk.|Molecular Biomedicine, LEO Pharma AS, Ballerup, Denmark. ewald@cbs.dtu.dk.|Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kgs. Lyngby, Denmark. ewald@cbs.dtu.dk.
authors.forename: David A
authors.initials: DA
authors.lastname: Ewald
authors.affiliation: The Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA. dana.malajian@gmail.com.|Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. dana.malajian@gmail.com.|Columbia University, College of Physicians and Surgeons, New York, NY, USA. dana.malajian@gmail.com.
authors.forename: Dana
authors.initials: D
authors.lastname: Malajian
authors.affiliation: The Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA. kruegej@rockefeller.edu.
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
authors.affiliation: Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kgs. Lyngby, Denmark. workman@cbs.dtu.dk.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Workman
authors.affiliation: School of Life Science, Jilin University, 2699 Qianjin Street, Changchun, Jilin, 130012, China. jiaolx@qq.com.
authors.forename: Tianjiao
authors.initials: T
authors.lastname: Wang
authors.affiliation: School of Life Science, Jilin University, 2699 Qianjin Street, Changchun, Jilin, 130012, China. windytian@hotmail.com.
authors.forename: Suyan
authors.initials: S
authors.lastname: Tian
authors.affiliation: Molecular Biomedicine, LEO Pharma AS, Ballerup, Denmark. thomas.litman@leo-pharma.com.
authors.forename: Thomas
authors.initials: T
authors.lastname: Litman
authors.affiliation: The Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA. eguttman@rockefeller.edu.|Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. eguttman@rockefeller.edu.
authors.forename: Emma
authors.initials: E
authors.lastname: Guttman-Yassky
authors.affiliation: The Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA. farinam@rockefeller.edu.|Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. farinam@rockefeller.edu.|Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. farinam@rockefeller.edu.|Icahn Institute for Genomics and Multiscale Biology at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, NY, USA. farinam@rockefeller.edu.
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
mesh_terms: D050197:Atherosclerosis / Q000150:complications*; D003876:Dermatitis, Atopic / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods*; D053263:Gene Regulatory Networks; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D018418:Th2 Cells / Q000276:immunology