Journal Article

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

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

2017

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/250/98 / 692/308/53/2421 / Angiogenesis / Arteriosclerosis / Atherosclerosis / Atopic dermatitis / Blood / Cardiovascular diseases / CCL17 protein / CCL20 protein / CCL22 protein / CD40L protein / CD6 antigen / Cell activation / CXCL10 protein / CXCL11 protein / Dermatitis / E-selectin / Eczema / Health risks / Humanities and Social Sciences / Inflammation / Interleukin 10 / Interleukin 12 / Interleukin 13 / Interleukin 16 / Interleukin 7 / Lymphocytes T / multidisciplinary / Proteins / Psoriasis / Science / Science (multidisciplinary) / Skin diseases / Vascular endothelial growth factor