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

Claudia C V Lang; Yael Renert-Yuval; Ester Del Duca; Ana B Pavel; Jianni Wu; Ning Zhang; Celina Dubin; Ashley Obi; Mashkura Chowdhoury; Madeline Kim; Yeriel D Estrada; James G Krueger; Hashim Kaderbhai; George Semango; Peter Schmid-Grendelmeier; Marie-Charlotte Brüggen; John E Masenga; Emma Guttman-Yassky

doi:10.1016/j.anai.2021.04.023

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

Ann Allergy Asthma Immunol. 2021 Sep;127(3):334-341. doi: 10.1016/j.anai.2021.04.023. Epub 2021 May 9.

Authors

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

Affiliations

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: [email protected].

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 (T_H2) (interleukin 13 [IL-13], IL-10, IL-4R, CCL13,CCL17,CCL18,CCL26) and T_H22 (IL22, S100As) pathways. Markers related to T_H17 and IL-23 (IL-17A, IL-23A, IL-12, PI3, DEFB4B) and T_H1 (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 T_H2 and T_H22 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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Black People / genetics
Black or African American
Cytokines / immunology
Dermatitis, Atopic / ethnology
Dermatitis, Atopic / genetics
Dermatitis, Atopic / immunology*
Female
Filaggrin Proteins
Gene Expression
Humans
Lipid Metabolism / genetics
Male
Phenotype
Severity of Illness Index
Skin / immunology*
Tanzania

Substances

Cytokines
FLG protein, human
Filaggrin Proteins

Grants and funding

UL1 TR001866/TR/NCATS NIH HHS/United States