TY - JOUR
T1 - Immune and barrier characterization of atopic dermatitis skin phenotype in Tanzanian patients
AU - Lang, Claudia C.V.
AU - Renert-Yuval, Yael
AU - Del Duca, Ester
AU - Pavel, Ana B.
AU - Wu, Jianni
AU - Zhang, Ning
AU - Dubin, Celina
AU - Obi, Ashley
AU - Chowdhoury, Mashkura
AU - Kim, Madeline
AU - Estrada, Yeriel D.
AU - Krueger, James G.
AU - Kaderbhai, Hashim
AU - Semango, George
AU - Schmid-Grendelmeier, Peter
AU - Brüggen, Marie Charlotte
AU - Masenga, John E.
AU - Guttman-Yassky, Emma
N1 - Publisher Copyright:
© 2021 American College of Allergy, Asthma & Immunology
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85107152963&partnerID=8YFLogxK
U2 - 10.1016/j.anai.2021.04.023
DO - 10.1016/j.anai.2021.04.023
M3 - Article
C2 - 33975024
AN - SCOPUS:85107152963
SN - 1081-1206
VL - 127
SP - 334
EP - 341
JO - Annals of Allergy, Asthma and Immunology
JF - Annals of Allergy, Asthma and Immunology
IS - 3
ER -