title: The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization.
abstract: 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. TH2 skewing characterized both Asian and EA patients with AD but not patients with psoriasis. Significantly higher TH17 and TH22 (IL17A, IL19, and S100A12 in lesional and IL-22 in nonlesional skin; P < .05) and lower TH1/interferon (CXCL9, CXCL10, MX1, and IFNG in nonlesional skin; P < .05) gene induction typified AD skin in Asian patients.
  
  
  CONCLUSIONS
  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 TH17 activation, and a strong TH2 component. The relative pathogenic contributions of the TH17 and TH2 axes in creating the Asian AD phenotype need to be tested in future clinical trials with appropriate targeted therapeutics.
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY.
authors.forename: Shinji
authors.initials: S
authors.lastname: Noda
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY; Department of Genetics and Genomics Science, Icahn Institute for Genomics and Multiscale Biology, New York, NY.
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ungar
authors.affiliation: Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Soo Jung
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Division of Biology and Biomedical Sciences, Washington University, St Louis, Mo.
authors.forename: Cristina
authors.initials: C
authors.lastname: de Guzman Strong
authors.affiliation: Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Yeriel D
authors.initials: YD
authors.lastname: Estrada
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Saeko
authors.initials: S
authors.lastname: Nakajima
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Honda
authors.affiliation: Department of Dermatology & Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jung U
authors.initials: JU
authors.lastname: Shin
authors.affiliation: Department of Dermatology & Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hemin
authors.initials: H
authors.lastname: Lee
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY.
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
authors.affiliation: Department of Dermatology & Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Kwang-Hoon
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kabashima
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address: Emma.Guttman@mountsinai.org.
authors.forename: Emma
authors.initials: E
authors.lastname: Guttman-Yassky
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000208:ethnology* / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D025341:Principal Component Analysis; D011565:Psoriasis / Q000208:ethnology* / Q000276:immunology*; D012867:Skin / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D044465:White People; D055815:Young Adult
chemical_list: D016207:Cytokines; D007073:Immunoglobulin E
keywords: Asian; Atopic dermatitis; European American; T(H)1; T(H)17; T(H)2; T(H)22; acanthosis; parakeratosis; psoriasis