Distinct transcriptomic profiles of early-onset atopic dermatitis in blood and skin of pediatric patients

Patrick M. Brunner, Ariel Israel, Alexandra Leonard, Ana B. Pavel, Hyun Je Kim, Ning Zhang, Tali Czarnowicki, Krishna Patel, Morgan Murphrey, Kara Ramsey, Stephanie Rangel, Rema Zebda, Vinaya Soundararajan, Xiuzhong Zheng, Yeriel D. Estrada, Hui Xu, James G. Krueger, Amy S. Paller, Emma Guttman-Yassky*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Background: Atopic dermatitis (AD) predominantly affects young children, but our understanding of AD pathogenesis is based on skin and blood samples from long-standing adult AD. Genomic biopsy profiling from early pediatric AD showed significant Th2 and Th17/Th22-skewing, without the characteristic adult Th1 up-regulation. Because obtaining pediatric biopsies is difficult, blood gene expression profiling may provide a surrogate for the pediatric skin signature. Objective: To define the blood profile and associated biomarkers of early moderate-to-severe pediatric AD. Methods: We compared microarrays and reverse transcription polymerase chain reaction (RT-PCR) of blood cells from 28 AD children (<5 years and within 6 months of disease onset) to healthy control blood cells. Differentially expressed genes (DEGs) in blood (fold change [FCH] > 1.2 and false discovery rate [FDR] < 0.05) were then compared with skin DEGs. Results: Eosinophil and Th2 markers (IL5RA, IL1RL1/ST2, HRH4, CCR3, SIGLEC8, PRSS33, CLC from gene arrays; IL13/IL4/CCL22 from RT-PCR) were up-regulated in early pediatric AD blood, whereas IFNG/Th1 was decreased. Th1 markers were negatively correlated with clinical severity (EASI, pruritus, transepidermal water loss [TEWL]), whereas Th2/Th17-induced interleukin (IL)-19 was positively correlated with SCORAD. Although a few RT-PCR–defined immune markers (IL-13/CCL22) were increased in blood, as previously also reported for skin, minimal overlap based on gene array DEGs was seen. Conclusion: The whole blood signature of early moderate-to-severe pediatric AD blood cells show predominantly a Th2/eosinophil profile; however, markers largely differ from the skin profile. Given their complementarity, pooling of biomarkers from blood and skin may improve profiling and predictions, providing insight regarding disease course, allergic comorbidity development, and response to systemic medications.

Original languageEnglish (US)
Pages (from-to)318-330.e3
JournalAnnals of Allergy, Asthma and Immunology
Volume122
Issue number3
DOIs
StatePublished - Mar 2019

Funding

Disclosures: Dr. Brunner is an employee of the Rockefeller University and has received personal fees from LEO Pharma, Pfizer, and Sanofi Genzyme. Dr. Zebda received fellowship support from Pfizer. Dr. Krueger is an employee of the Rockefeller University and has received research support (grants paid to his institution) or personal fees from Pfizer, Amgen, Janssen, Lilly, Merck, Novartis, Kadmon, Dermira, Boehringer, Innovaderm, Kyowa, BMS, Serono, BiogenIdec, Delenex, AbbVie, Sanofi, Baxter, Paraxel, Xenoport, and Kineta. Dr. Paller is an investigator for Leo, Incyte, and Sanofi/Regeneron (grants paid to Northwestern University) and has received honoraria related to AD consulting from AbbVie, Amgen, Asana, Boehringer, Dermavant, Dermira, Eli Lilly, Forte, Galderma, Leo, Matrisys, Menlo Therapeutics, Morphosys/Galapagos, Novartis, Pfizer, Regeneron, Sanofi-Genzyme, and Valeant. Dr. Guttman-Yassky is an employee of Mount Sinai and has received research funds (grants paid to her institution) from Abbvie, Celgene, Eli Lilly, Janssen, Medimmune/Astra Zeneca, Novartis, Pfizer, Regeneron, Vitae, Glenmark, Galderma, Asana, Innovaderm, Dermira, and UCB. Dr. Guttman-Yassky is also a consultant for Sanofi Aventis, Regeneron, Stiefel/GlaxoSmithKline, MedImmune, Celgene, Anacor, AnaptysBio, Dermira, Galderma, Glenmark, Novartis, Pfizer, Vitae, Leo Pharma, Abbvie, Eli Lilly, Kyowa, Mitsubishi Tanabe, Asana Biosciences, and Promius. The rest of the authors declare that they have no relevant conflicts of interest.Funding Sources: This work was funded by a research grant from the LEO Foundation. Dr. Brunner was supported in part by grant # UL1 TR00043 from the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program. Dr. Zebda was supported by a Dermatology Fellowship Grant from Pfizer. The study was also supported by the Northwestern Skin Disease Research Center (NIAMS P30 AR057216) and the Northwestern University Clinical And Translational Sciences (NUCATS) Institute (UL1TR001422). Funding Sources: This work was funded by a research grant from the LEO Foundation . Dr. Brunner was supported in part by grant # UL1 TR00043 from the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program. Dr. Zebda was supported by a Dermatology Fellowship Grant from Pfizer . The study was also supported by the Northwestern Skin Disease Research Center ( NIAMS P30 AR057216 ) and the Northwestern University Clinical And Translational Sciences (NUCATS) Institute ( UL1TR001422 ).

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Immunology and Allergy
  • Immunology

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