Abstract
BackgroundAtopic 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.MethodsWe carried out a meta-analysis combining 4 published AD datasets to define a robust disease profile, termed meta-analysis derived AD (MADAD) transcriptome.ResultsThis 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.ConclusionsOur meta-analysis provides novel and powerful insights into AD disease pathology, and reinforces the concept of AD as a systemic disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-015-0133-x) contains supplementary material, which is available to authorized users.
Highlights
Atopic dermatitis (AD) is a common inflammatory skin disease with limited treatment options
Indices) or Immunoglobulin E (IgE) levels were found across patients who all had moderate-to-severe AD (SCORAD > 25; EASI > 12)
The Meta-analysis-derived AD (MADAD) transcriptome Applying the meta-analysis approach to 4 studies and 97 samples, we identified a set of 595 differentially expressed genes (DEGs) (387 up- and 208 downregulated) using the classical |FCH| ≥ 2 and false discovery rate (FDR) ≤ 0.05 criteria, representing a robust profile defined as the meta-analysis derived AD (MADAD) transcriptome
Summary
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. 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. Immune and barrier abnormalities characterize AD, with Th2/Th22 cytokine activation, increased hyperplasia and significant decreases in differentiation markers. These observations have led to two competing pathogenic hypotheses [1, 8, 9], recent studies. Genomic profiling may be used to predict therapeutic responses, as in juvenile idiopathic arthritis, in which profiling correctly predicted therapeutic responses at 6 months [19]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
