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

ABSTRACT:

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 TH22 (IL22, S100As) pathways. Markers related to TH17 and IL-23 (IL-17A, IL-23A, IL-12, PI3, DEFB4B) and TH1 (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 TH2 and TH22 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.

SUBMITTER: Lang CCV 

PROVIDER: S-EPMC11344219 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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

Lang Claudia C V CCV   Renert-Yuval Yael Y   Del Duca Ester E   Pavel Ana B AB   Wu Jianni J   Zhang Ning N   Dubin Celina C   Obi Ashley A   Chowdhoury Mashkura M   Kim Madeline M   Estrada Yeriel D YD   Krueger James G JG   Kaderbhai Hashim H   Semango George G   Schmid-Grendelmeier Peter P   Brüggen Marie-Charlotte MC   Masenga John E JE   Guttman-Yassky Emma E  

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 20210509 3

<h4>Background</h4>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.<h4>Objective</h4>To characterize the skin prof  ...[more]