The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH 17 polarization

• Published in: Journal of allergy and clinical immunology Vol. 136; no. 5; pp. 1254 - 1264
• Main Authors: Noda, Shinji, MD, PhD, Suárez-Fariñas, Mayte, PhD, Ungar, Benjamin, BA, Kim, Soo Jung, MD, PhD, de Guzman Strong, Cristina, PhD, Xu, Hui, MSc, Peng, Xiangyu, MSc, Estrada, Yeriel D., BSc, Nakajima, Saeko, MD, PhD, Honda, Tetsuya, MD, PhD, Shin, Jung U., MD, Lee, Hemin, MD, Krueger, James G., MD, PhD, Lee, Kwang-Hoon, MD, PhD, Kabashima, Kenji, MD, PhD, Guttman-Yassky, Emma, MD, PhD
• Format: Journal Article
• Language: English
• Published: 2015
• Subjects: Allergy and Immunology; FLG; Immunohistochemistry; IHC; Filaggrin; T H17; Asian; T H2; T H1; T H22; European American; Real-time PCR; Atopic dermatitis; RT-PCR; parakeratosis; EA; Fold change; Dendritic cell; AD; STAT1; Signal transducer and activator of transcription 1; FCH; PCA; Langerhans cell; psoriasis; LC; acanthosis; DC; Principal component analysis
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2015.08.015

Background Atopic dermatitis (AD) shows very high prevalence in Asia, with a large unmet need for effective therapeutics. Direct comparisons between European American (EA) and Asian patients with AD are unavailable, but earlier blood studies detected increased IL-17+ –producing cell counts in Asian patients with AD. Objective We sought to characterize the Asian AD skin phenotype and compare it with the EA AD skin phenotype. Methods We performed genomic profiling (real-time PCR) and immunohistochemistry on lesional and nonlesional biopsy specimens from 52 patients with AD (25 EAs and 27 Asians), 10 patients with psoriasis (all EAs), and 27 healthy subjects (12 EAs and 15 Asians). Results Although disease severity/SCORAD scores were similar between the AD groups (58.0 vs 56.7, P  = .77), greater acanthosis, higher Ki67 counts, and frequent parakeratosis were characteristics of lesional epidermis from Asian patients with AD ( P  < .05). Most (24/27) Asian patients had high IgE levels. A principal component analysis using real-time PCR data clustered the Asian AD phenotype between the EA AD and psoriasis phenotypes. TH 2 skewing characterized both Asian and EA patients with AD but not patients with psoriasis. Significantly higher TH 17 and TH 22 ( IL17A, IL19 , and S100A12 in lesional and IL-22 in nonlesional skin; P  < .05) and lower TH 1/interferon ( CXCL9, CXCL10, MX1 , and IFNG in nonlesional skin; P  < .05) gene induction typified AD skin in Asian patients. Conclusion The Asian AD phenotype presents (even in the presence of increased IgE levels) a blended phenotype between that of EA patients with AD and those with psoriasis, including increased hyperplasia, parakeratosis, higher TH 17 activation, and a strong TH 2 component. The relative pathogenic contributions of the TH 17 and TH 2 axes in creating the Asian AD phenotype need to be tested in future clinical trials with appropriate targeted therapeutics.