Serum proteomic characterization of the East Asian and Asian American atopic dermatitis molecular phenotype

Summary: Abstract Body: Atopic dermatitis (AD) is a heterogenous disease characterized by universal Th2-skewing and variable Th1, Th17, and Th22 immune activation, and barrier dysfunction, amongst patients of different ancestries. These heterogeneities have suggested that both environmental and genetic factors may contribute to progression and severity of disease suggesting the need for more tailored and individualized treatments. Comparing the American Asian (AA) AD phenotype to the East Asian (EA) phenotype to understand their similarities and differences, with appropriate comparison to a Caucasian American cohort, has not been evaluated, and we aim to bridge this gap. We performed proteomic serum analysis on blood samples from 43 patients with AD (18 EA, 13 AA, 12 White) and 29 ethnicity matched controls (9 EA, 9 AA, 11 White) via the OLINK platform. Differentially expressed proteins (DEPs) were defined as fold change > 1.5 and false discovery rate <.05. Across ethnicities there were common upregulations in Th2 associated genes (CCL13, CCL17), general inflammatory genes (MMP12) and T cell activation (IL18, TNFSF14). However, we found several DEPs between EA and AA. While both EA and AA AD patients demonstrated upregulation of Th1 genes (IL1RA, IL2RA), EA AD showed additional skewing of Th1-related genes (CXCL9/10/11). Th17 activation was also stronger in EA AD patients (CXCL1, CCL20, PI3), while genes related to cellular regulation (NFkB, STAMBP, AXIN1) and apoptosis (SIRT2) were unique to AA. Dysregulation of genes associated with barrier function and atherosclerosis were shared amongst EA and AA AD patients (PI3, EZR, IL16). Our findings expand on the current knowledge of AD profiles. While prior characterizations have not taken into account environmental and migration differences within ethnicities, proteomic profiles of native and corresponding immigrant communities may indicate diverging ancestries and potentiates more targeted and individualized therapies. Daniel Liu¹, Ester Del Duca¹, Megan Lau¹, Joseph A. Largen¹, Yeriel Estrada¹, Emma Guttman-Yassky¹ 1. Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, United States. Minoritized Populations and Health Disparities Research