Atopic dermatitis in African American patients is TH2/TH22-skewed with TH1/TH17 attenuation

被引：158

作者：

Sanyal, Riana D. ^{[1
]}

Pavel, Ana B. ^{[1
]}

Glickman, Jacob ^{[1
]}

Chan, Tom C. ^{[1
,2
,3
]}

Zheng, Xiuzhong ^{[3
]}

Zhang, Ning ^{[1
]}

Cueto, Inna ^{[3
]}

Peng, Xiangyu ^{[1
]}

estrada, Yeriel ^{[1
]}

Fuentes-Duculan, Judilyn ^{[3
]}

Alexis, Andrew F. ^{[4
]}

Krueger, James G. ^{[3
]}

Guttman-Yassky, Emma ^{[1
]}

机构：

[1] Icahn Sch Med Mt Sinai, Dept Dermatol, Lab Inflammatory Skin Dis, 5 E 98th St, New York, NY 10029 USA

[2] Natl Taiwan Univ Hosp & Coll Med, Dept Dermatol, Taipei, Taiwan

[3] Rockefeller Univ, Lab Invest Dermatol, 1230 York Ave, New York, NY 10021 USA

[4] Mt Sinai St Lukes & Mt Sinai West, Dept Dermatol, New York, NY USA

来源：

ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY | 2019年 / 122卷 / 01期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; UNITED-STATES; TOTAL IGE; EPIDERMAL DIFFERENTIATION; SKIN; FILAGGRIN; PROTEINS; BARRIER; IMMUNE; ECZEMA;

D O I：

10.1016/j.anai.2018.08.024

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

BACKGROUND: African Americans (AA) are disproportionately impacted by atopic dermatitis (AD), with increased prevalence and therapeutic challenges unique to this population. Molecular profiling data informing development of targeted therapeutics for AD are derived primarily from European American (EA) patients. These studies are absent in AA, hindering development of effective treatments for this population. OBJECTIVE: We sought to characterize the global molecular profile of AD in the skin of AA patients as compared with that of EA AD and healthy controls. METHODS: We performed RNA-Seq with reverse transcription polymerase chain reaction validation and immunohistochemistry studies in lesional and nonlesional skin of AA and EA AD patients vs healthy controls. RESULTS: African American AD lesions were characterized by greater infiltration of dendritic cells (DCs) marked by the high-affinity immunoglobulin E (IgE) receptor (Fc epsilon R1+) compared with EA AD (P < .05). Both AD cohorts showed similarly robust up-regulation of Th2-related (CCL17/18/26) and Th22-related markers (interleukin [IL]-22, S100A8/9/12), but AA AD featured decreased expression of innate immune (tumor necrosis factor [TNF], IL-1 beta), Th1-related (interferon gamma [IFN-gamma], MX1, IL-12RB1), and Th17-related markers (IL-23p19, IL-36G, CXCL1) vs EA AD (P < .05). The Th2 (IL-13) and Th22-related products (IL-22, S100A8/9/12) and serum IgE were significantly correlated with clinical severity (Scoring of Atopic Dermatitis [SCORAD]) in AA. Fillagrin (FLG) was exclusively down-regulated in EA AD, whereas loricrin (LOR) was down-regulated in both AD cohorts and negatively correlated with SCORAD in AA. CONCLUSION: The molecular phenotype of AA AD skin is characterized by attenuated Th1 and Th17 but similar Th2/Th22-skewing to EA AD. Our data encourages a personalized medicine approach accounting for phenotype-specific characteristics in future development of targeted therapeutics and clinical trial design for AD. (c) 2018 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

引用

页码：99 / +

页数：18

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