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

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.

• Authors: 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
• Journal: Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (Ann Allergy Asthma Immunol) Vol. 122 Issue 3 Pg. 318-330.e3 (03 2019) ISSN: 1534-4436 [Electronic] United States
• PMID: 30508584 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers

Topics

• Age of Onset
• Biomarkers (analysis)
• Biopsy
• Child, Preschool
• Dermatitis, Atopic (blood, genetics)
• Female
• Gene Expression Profiling
• Humans
• Infant
• Leukocytes, Mononuclear (metabolism)
• Male
• Skin (metabolism)
• Transcriptome