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. 2017 Aug 18;7(1):8707.
doi: 10.1038/s41598-017-09207-z.

The atopic dermatitis blood signature is characterized by increases in inflammatory and cardiovascular risk proteins

Patrick M Brunner  1 , Mayte Suárez-Fariñas  2   3   4 , Helen He  2 , Kunal Malik  2 , Huei-Chi Wen  2 , Juana Gonzalez  1 , Tom Chih-Chieh Chan  2 , Yeriel Estrada  2 , Xiuzhong Zheng  1 , Saakshi Khattri  2 , Annunziata Dattola  1 , James G Krueger  1 , Emma Guttman-Yassky  5   6
Affiliations

The atopic dermatitis blood signature is characterized by increases in inflammatory and cardiovascular risk proteins

Patrick M Brunner et al. Sci Rep. .

Erratum in

Abstract

Beyond classic "allergic"/atopic comorbidities, atopic dermatitis (AD) emerges as systemic disease with increased cardiovascular risk. To better define serum inflammatory and cardiovascular risk proteins, we used an OLINK high-throughput proteomic assay to analyze moderate-to-severe AD (n = 59) compared to psoriasis (n = 22) and healthy controls (n = 18). Compared to controls, 10 proteins were increased in serum of both diseases, including Th1 (IFN-γ, CXCL9, TNF-β) and Th17 (CCL20) markers. 48 proteins each were uniquely upregulated in AD and psoriasis. Consistent with skin expression, AD serum showed up-regulation of Th2 (IL-13, CCL17, eotaxin-1/CCL11, CCL13, CCL4, IL-10), Th1 (CXCL10, CXCL11) and Th1/Th17/Th22 (IL-12/IL-23p40) responses. Surprisingly, some markers of atherosclerosis (fractalkine/CX3CL1, CCL8, M-CSF, HGF), T-cell development/activation (CD40L, IL-7, CCL25, IL-2RB, IL-15RA, CD6) and angiogenesis (VEGF-A) were significantly increased only in AD. Multiple inflammatory pathways showed stronger enrichment in AD than psoriasis. Several atherosclerosis mediators in serum (e.g. E-selectin, PI3/elafin, CCL7, IL-16) correlated with SCORAD, but not BMI. Also, AD inflammatory mediators (e.g. MMP12, IL-12/IL-23p40, CXCL9, CCL22, PI3/Elafin) correlated between blood and lesional as well as non-lesional skin. Overall, the AD blood signature was largely different compared to psoriasis, with dysregulation of inflammatory and cardiovascular risk markers, strongly supporting its systemic nature beyond atopic/allergic association.

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Conflict of interest statement

PMB has received personal fees from LEO Pharma and Sanofi. MSF has received research support from Pfizer and Quorum Consulting. JGK has received research support (grants paid to his institution) and/or personal fees from Pfizer, Amgen, Janssen, Lilly, Merck, Novartis, Kadmon, Dermira, Boehringer, Innovaderm, Kyowa, BMS, Serono, BiogenIdec, Delenex, AbbVie, Sanofi, Baxter, Paraxel, Xenoport, and Kineta. EGY is a board member for Sanofi Aventis,Regeneron,Stiefel/GlaxoSmithKline,MedImmune, Celgene, Anacor, AnaptysBio, Celsus, Dermira,Galderma,Glenmark,Novartis, Pfizer, Vitae, Leo Pharma, Abbvie and Asana Biosciences; has received consultancy fees from Regeneron, Sanofi, MedImmune, Celgene, Stiefel/GlaxoSmithKline, Celsus, BMS, Amgen, Drais, AbbVie, Anacor, AnaptysBio, Dermira, Galderma, Glenmark, LEO Pharma, Novartis, Pfizer, Vitae, Mitsubishi Tanabe, Eli Lilly, Abbvie, and Asana Biosciences; and has received research support from Janssen, Regeneron, Celgene, BMS, Novartis, Merck, LEO Pharma, Dermira, Glenmark, Innovaderm, and UCB. The rest of the authors declare that they have no relevant conflicts of interest.

Figures

Figure 1
Figure 1
Regulation of inflammatory and cardiovascular risk proteins in AD and psoriasis vs. healthy controls. Venn diagrams of regulated serum proteins compared to healthy controls, adjusted for age/gender (a) and age/gender/BMI (b). Markers that were significantly upregulated (FCH > 1.3, FDR < 0.1) in both AD and psoriasis (c), only in AD (d) or only in psoriasis (e) are depicted as log2 fold change over healthy control serum with their 95% confidence intervals.
Figure 2
Figure 2
Blood protein correlations with skin disease severity (SCORAD, BSA) and BMI. Pearson correlation coefficients of AD serum proteins significantly correlated with SCORAD (a) and body surface area/BSA (b), and their respective scatter plots (c–j), as well as leptin (k–l), in comparison to correlations with body mass index/BMI.
Figure 3
Figure 3
Blood-skin comparisons. Fold change comparisons of AD serum protein levels (AD vs. healthy controls) and skin MADAD transcriptome levels (lesional vs. non-lesional AD).
Figure 4
Figure 4
Blood-skin correlations of inflammatory mediators. Correlation plots of selected serum protein levels with their corresponding lesional and non-lesional skin mRNA levels (a–j); scatterplots with estimated linear regression and 95% confidence interval; r Pearson correlation; ρ Spearman correlation.
Figure 5
Figure 5
Pathway analysis. Selected pathways enriched in AD and psoriasis serum, compared to respective healthy controls; the green line indicates false discovery rate/FDR < 0.05.
See this image and copyright information in PMC

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