Immune and barrier characterization of atopic dermatitis skin phenotype in Tanzanian patients

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 (TH2) (interleukin 13 [IL-13], IL-10, IL-4R, CCL13,CCL17,CCL18,CCL26) and T(H)22 (IL22, S100As) pathways. Markers related to T(H)17 and IL-23 (IL-17A, IL-23A, IL-12, PI3, DEFB4B) and T(H)1 (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 patientswith AD is consistentwith that of African Americans, exhibiting dominant T(H)2 and T(H)22 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 fromthese underrepresented populations. (C) 2021 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Automated summary

The study characterized the skin profile of AD patients from Tanzania, revealing significant up-regulation of key mediators in both T(H)2 and T(H)22 pathways, as well as robust attenuation of lipid metabolism genes in the skin.