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

BACKGROUND Atopic dermatitis/AD is a common disease, with particularly high prevalence seen in Africa. It is increasingly recognized that AD patients of different ethnic backgrounds have unique molecular signatures in skin, potentially accounting for treatment response variations. However, the skin profile of AD patients from Africa is unknown, hindering development of new treatments targeted to this patient population. OBJECTIVE To characterize the skin profile of AD patients from Africa. METHODS Gene-expression studies including RNA-sequencing (using threshold of foldchange/FCH>2 and false discovery rate/FDR<0.05) and real-time PCR were performed on skin biopsies of Tanzanian moderate-to-severe AD patients and controls. RESULTS Tanzanian AD skin presented robust up-regulations of multiple key mediators of both Th2 (IL-13, IL10, IL-4R, CCL13/CCL17/CCL18/CCL26) and Th22 (IL22, S100As) pathways. Markers related to Th17/IL-23 (IL-17A, IL-23p19/IL-23A, IL-23p40/IL-12, PI3, DEFB4B) and Th1 (IFNγ, CXCL9/CXCL10/CXCL11) were also significantly overexpressed in AD tissues, albeit to a lesser extent. IL-36 isoforms showed significant upregulations in African skin. The barrier fingerprint of Tanzanian AD showed no suppression of hallmark epidermal barrier differentiation genes, such as filaggrin/FLG, loricrin/LOR, and periplakin/PPL, with robust attenuation of lipid metabolism genes (i.e AWAT1). CONCLUSION The skin phenotype of Tanzanian AD patients is consistent with that of African-Americans, exhibiting dominant Th2/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, as well as the need to develop unique treatments targeting AD patients of these under-represented populations.