Claudia C V Lang1, Yael Renert-Yuval2, Ester Del Duca3, Ana B Pavel4, Jianni Wu5, Ning Zhang5, Celina Dubin5, Ashley Obi5, Mashkura Chowdhoury5, Madeline Kim5, Yeriel D Estrada5, James G Krueger6, Hashim Kaderbhai7, George Semango8, Peter Schmid-Grendelmeier9, Marie-Charlotte Brüggen10, John E Masenga8, Emma Guttman-Yassky11. 1. 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. 2. 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. 3. 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. 4. 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. 5. Laboratory of Inflammatory Skin Diseases, Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York. 6. Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York. 7. Department of Dermatology, M.P. Shah Hospital, Nairobi, Kenya; Department of Dermatology, Regional Dermatology Training Center, Moshi, Tanzania. 8. Department of Dermatology, Regional Dermatology Training Center, Moshi, Tanzania. 9. Department of Dermatology, University Hospital Zürich, Zürich, Switzerland. 10. Department of Dermatology, University Hospital Zürich, Zürich, Switzerland; Hochgebirgsklinik Davos, Davos, Switzerland. 11. Laboratory of Inflammatory Skin Diseases, Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: Emma.Guttman@mountsinai.org.
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.
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.