Immune and barrier characterization of atopic dermatitis skin phenotype in Tanzanian patients,Annals of Allergy, Asthma & Immunology

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Immune and barrier characterization of atopic dermatitis skin phenotype in Tanzanian patients
Annals of Allergy, Asthma & Immunology ( IF 5.9 ) Pub Date : 2021-05-09 , DOI: 10.1016/j.anai.2021.04.023
Claudia C V Lang ₁ , Yael Renert-Yuval ₂ , Ester Del Duca ₃ , Ana B Pavel ₄ , Jianni Wu ₅ , Ning Zhang ₅ , Celina Dubin ₅ , Ashley Obi ₅ , Mashkura Chowdhoury ₅ , Madeline Kim ₅ , Yeriel D Estrada ₅ , James G Krueger ₆ , Hashim Kaderbhai ₇ , George Semango ₈ , Peter Schmid-Grendelmeier ₉ , Marie-Charlotte Brüggen ₁₀ , John E Masenga ₈ , Emma Guttman-Yassky ₅

Affiliation

Laboratory of Inflammatory Skin Diseases, Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Dermatology, University Hospital Zürich, Zürich, Switzerland.
Laboratory of Inflammatory Skin Diseases, Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York; Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York.
Laboratory of Inflammatory Skin Diseases, Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Dermatology, University of Magna Graecia, Catanzaro, Italy.
Laboratory of Inflammatory Skin Diseases, Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Biomedical Engineering, University of Mississippi, Oxford, Mississippi.
Laboratory of Inflammatory Skin Diseases, Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York.
Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York.
Department of Dermatology, M.P. Shah Hospital, Nairobi, Kenya; Department of Dermatology, Regional Dermatology Training Center, Moshi, Tanzania.
Department of Dermatology, Regional Dermatology Training Center, Moshi, Tanzania.
Department of Dermatology, University Hospital Zürich, Zürich, Switzerland.
Department of Dermatology, University Hospital Zürich, Zürich, Switzerland; Hochgebirgsklinik Davos, Davos, Switzerland.

Background

Atopic dermatitis (AD) is a common disease, with particularly high prevalence found in Africa. It is increasingly recognized that patients with AD of different ethnic backgrounds have unique molecular signatures in the skin, potentially accounting for treatment response variations. Nevertheless, the skin profile of patients with AD from Africa is unknown, hindering development of new treatments targeted to this patient population.

Objective

To characterize the skin profile of patients with AD from Africa.

Methods

Gene expression studies, including RNA sequencing (using threshold of fold change of >2 and false discovery rate of <0.05) and real-time polymerase chain reaction, were performed on skin biopsies of Tanzanian patients with moderate-to-severe AD and controls.

Results

Tanzanian AD skin presented robust up-regulations of multiple key mediators of both T helper 2 (T_H2) (interleukin 13 [IL-13], IL-10, IL-4R, CCL13,CCL17,CCL18,CCL26) and T_H22 (IL22, S100As) pathways. Markers related to T_H17 and IL-23 (IL-17A, IL-23A, IL-12, PI3, DEFB4B) and T_H1 (interferon gamma, CXCL9,CXCL10,CXCL11) were also significantly overexpressed in AD tissues (FDR<.05), albeit to a lesser extent. IL-36 isoforms revealed substantial up-regulations in African skin. The barrier fingerprint of Tanzanian AD revealed no suppression of hallmark epidermal barrier differentiation genes, such as filaggrin, loricrin, and periplakin, with robust attenuation of lipid metabolism genes (ie, AWAT1).

Conclusion

The skin phenotype of Tanzanian patients with AD is consistent with that of African Americans, exhibiting dominant T_H2 and T_H22 skewing, minimal dysregulation of terminal differentiation, and even broader attenuation of lipid metabolism-related products. These data highlight the unique characteristic of AD in Black individuals and the need to develop unique treatments targeting patients with AD from these underrepresented populations.

中文翻译：

坦桑尼亚患者特应性皮炎皮肤表型的免疫和屏障特征

背景

特应性皮炎 (AD) 是一种常见疾病，在非洲流行率特别高。人们越来越认识到，不同种族背景的 AD 患者在皮肤中具有独特的分子特征，这可能是治疗反应变化的原因。然而，来自非洲的 AD 患者的皮肤状况尚不清楚，这阻碍了针对该患者群体的新疗法的开发。

客观的

表征来自非洲的 AD 患者的皮肤特征。

方法

基因表达研究，包括 RNA 测序（使用 >2 的倍数变化阈值和 <0.05 的错误发现率）和实时聚合酶链反应，在坦桑尼亚中度至重度 AD 患者和对照的皮肤活检中进行。

结果

坦桑尼亚 AD 皮肤对 T 辅助细胞2 (T _H 2)（白介素 13 [IL-13]、IL-10、IL-4R、CCL13、CCL17、CCL18、CCL26）和 T _H的多种关键介质表现出强烈的上调22 (IL22, S100As) 通路。与 T _H 17 和 IL-23（IL-17A、IL-23A、IL-12、PI3、DEFB4B）和 T _H 1（干扰素 γ、CXCL9、CXCL10、CXCL11）相关的标志物也在 AD 组织 (FDR) 中显着过表达<.05)，尽管程度较小。IL-36 亚型在非洲皮肤中显着上调。坦桑尼亚 AD 的屏障指纹显示没有抑制标志性表皮屏障分化基因，如丝聚蛋白、loricrin 和 periplakin，脂质代谢基因（即 AWAT1）强烈衰减。