The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization

Shinji Noda, Mayte Suárez-Fariñas, Benjamin Ungar, Soo Jung Kim, Cristina De Guzman Strong, Hui Xu, Xiangyu Peng, Yeriel D. Estrada, Saeko Nakajima, Tetsuya Honda, Jung U. Shin, Hemin Lee, James G. Krueger, Kwang Hoon Lee, Kenji Kabashima, Emma Guttman-Yassky

Research output: Contribution to journalArticlepeer-review

249 Citations (Scopus)

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. 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 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.

Original languageEnglish
Pages (from-to)1254-1264
Number of pages11
JournalJournal of Allergy and Clinical Immunology
Volume136
Issue number5
DOIs
Publication statusPublished - 2015 Jul 9

Bibliographical note

Funding Information:
Disclosure of potential conflict of interest: S. Noda has received research support from the CTSA program. C. de Guzman Strong has received research support from the National Institutes of Health (NIH; R01 AR065523). J. G. Krueger has received research support (grants paid to his institution) and personal fees from Novartis, Pfizer, Janssen, Lilly, Merck, Kadmon, Dermira, Boehringer, BMS, and Paraxel during the conduct of the study and has received research support (grants paid to his institution) from Amgen, Innovaderm, and Kyowa and personal fees from Serono, BiogenIdec, Delenex, AbbVie, Sanofi, Baxter, Xenoport, and Kineta. E. Guttman-Yassky is a board member for Sanofi Aventis, Regeneron, Stiefel/GlaxoSmithKline, Medimmune, Celgene, Anacor, and Leo Pharma; has received consultancy fees from Regeneron, Sanofi Aventis, Medimmune, Celgene, Stiefel/GlaxoSmithKline, Celsus, BMS, Amgen, and Drais; and has received research support from Regeneron, Celgene, BMS, and Janssen. The rest of the authors declare that they have no relevant conflicts of interest.

Funding Information:
Supported by a research grant (EGY) from Leo Pharma . S.N., B.U., M.S.-F., and J.G.K. were supported by grant no. 5UL1RR024143-02 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and the NIH Roadmap for Medical Research . S.N. was supported in part by grant no. UL1 TR000043 from the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program.

Publisher Copyright:
© 2015 American Academy of Allergy, Asthma & Immunology.

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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