Meta-analysis derived atopic dermatitis (MADAD) transcriptome defines a robust AD signature highlighting the involvement of atherosclerosis and lipid metabolism pathways

BMC Medical Genomics

Mayte Suárez-Fariñas²  Emma Guttman-Yassky⁷  Thomas Litman³  Suyan Tian⁴  Tianjiao Wang⁴  Christopher T. Workman¹  James G. Krueger⁵  Dana Malajian⁶  David A. Ewald¹ 

[1] Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kgs. Lyngby, Denmark;Icahn Institute for Genomics and Multiscale Biology at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, NY, USA;Molecular Biomedicine, LEO Pharma AS, Ballerup, Denmark;School of Life Science, Jilin University, 2699 Qianjin Street, Changchun 130012, Jilin, China;The Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA;Columbia University, College of Physicians and Surgeons, New York, NY, USA;Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

关键词: Expression analysis;    Atherosclerosis;    Transcriptome;    Meta-analysis;    Atopic dermatitis;   

Others  :  1228950
DOI  :  10.1186/s12920-015-0133-x

 received in 2015-03-23, accepted in 2015-09-11,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Ewald et al.

【 图 表 】

Fig. 1.

Figure 3.

Fig. 3.

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