Ethnic Variations in Molecular Phenotypes of Patients With Atopic Dermatitis

Clinical features of atopic dermatitis (AD) vary in ethnic populations, with lesions from African American (AA) patients appearing darker and more difficult to distinguish clinically from nonlesional skin, when compared with lesions from European American (EA) individuals, according to a study published in Annals of Allergy, Asthma & Immunology.

The current analysis is the first global molecular profiling study of AD skin in AA patients using RNA-sequencing. The study findings characterized phenotypic variations among AA and EA AD cohorts.

The researchers differentiated the global molecular profile in skin from AA individuals with AD, EA individuals with AD, and healthy controls. They conducted RNA-sequencing with real-time polymerase chain reaction validation and immunohistochemistry analyses in lesional and nonlesional skin of AA and EA patients with AD compared with controls. Biopsy specimens were collected from lesional and nonlesional skin in 30 patients with chronic AD since childhood (15 AA patients and 15 EA patients), and from healthy skin of 16 controls (9 AA individuals and 7 EA individuals).

AD lesions in AA individuals were characterized by significantly greater infiltration of dendritic cells marked by the high-affinity immunoglobulin E receptor/(FcεR1+) compared with AD lesions among EA individuals (P <.05). Although both AA and EA AD cohorts demonstrated similarly robust upregulation of T helper (Th)2-related markers (CCL17/18/26) and Th22-related markers (interleukin [IL]-22, S100A8/9/12), AD among AA patients exhibited significantly decreased expression of innate immune-related markers (tumor necrosis factor, IL-1β); Th1-related markers (interferon-γ), MX1,
IL-12RB1); and Th17-related markers (IL-23p19, IL-36G, CXCL1) vs AD among EA patients (P <.05).

In addition, Th2-related products (IL-13) and Th22-related products (IL-22, S100A8/9/12), as well as serum immunoglobulin E, were all significantly associated with clinical disease severity based on Scoring of Atopic Dermatitis in AA patients. Filaggrin was exclusively downregulated in EA patients with AD, whereas loricrin was downregulated in both AD cohorts (AA and EA), and was negatively correlated with Scoring of Atopic Dermatitis in AA patients with AD.

The investigators concluded that the molecular phenotype in AA patients with AD is characterized by attenuated Th1 and Th17 cells, but by Th2/Th22 skewing that is similar to that among EA patients with AD. The data from this study support a personalized approach to medicine, taking into consideration phenotype-specific characteristics in future AD targeted therapeutic clinical trial by ethnicity to better comprehend whether ethnic variations in AD molecular phenotypes translate to differential treatment responses to polar T-cell antagonism.

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Reference

Sanyal RD, Pavel AB, Glickman J, et al. Atopic dermatitis in African American patients is T_H2/T_H22-skewed with T_H1/T_H17 attenuation [published online September 6, 2018]. Ann Allergy Asthma Immunol. doi: 10.1016/j.anai.2018.08.024