The blood proteomic signature of early-onset pediatric atopic dermatitis shows systemic inflammation and is distinct from adult long-standing disease

JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY

卷:81

Article

Brunner, Patrick M.¹  He, Helen^2,3  Pavel, Ana B.^2,3  Czarnowicki, Tali^1,2,3  Lefferdink, Rachel⁴  Erickson, Taylor⁴  Canter, Talia⁴  Puar, Neha⁴  Rangel, Stephanie M.⁴  Malik, Kunal^2,3  Estrada, Yeriel^2,3  Krueger, James G.¹  Guttman-Yassky, Emma^1,2,3  Paller, Amy S.⁴ 

[1] Rockefeller Univ, Lab Invest Dermatol, 1230 York Ave, New York, NY 10021 USA

[2] Icahn Sch Med Mt Sinai, Dept Dermatol, New York, NY 10029 USA

[3] Icahn Sch Med Mt Sinai, Lab Inflammatory Skin Dis, New York, NY 10029 USA

[4] Northwestern Univ, Feinberg Sch Med, Dept Dermatol, 676 N St Clair St, Chicago, IL 60611 USA

关键词: Atopic dermatitis;    infant;    multiplex assay;    Olink;    pediatric;    peripheral blood;    proximity extension assay;   

DOI  :  10.1016/j.jaad.2019.04.036

来源: Elsevier

【 摘 要 】

Background: Despite increasing evidence that adults with long-standing atopic dermatitis (AD) have systemic inflammation, little is known about systemic inflammation in recent-onset early pediatric AD. Objective: To analyze blood inflammatory proteins of early pediatric AD. Methods: Using high-throughput proteomics (proximity extension assay), we assessed 257 inflammatory and cardiovascular risk proteins in the blood of 30 children with moderate to severe AD younger than 5 years of age (within 6 months of onset) compared with age-matched pediatric control individuals and adult patients with AD. Results: In pediatric AD blood, T helper (Th) type 2 (CCL13, CCL22) and Th17 (peptidase inhibitor-3/elafin) markers were increased, together with markers of tissue remodeling (matrix metalloproteinases 3/9/10, urokinase receptor), endothelial activation (E-selectin), T-cell activation (IL2RA), neutrophil activation (myeloperoxidase), lipid metabolism (FABP4), and growth factors (FGF21, transforming growth factor-alpha). Total numbers of dysregulated proteins were smaller in pediatric AD (n = 22) than in adult AD (n = 61). Clinical severity scores were positively correlated with receptors for interleukins 33 and 36 and inversely correlated with some Th1 markers (interferon gamma, CXCL11). Limitations: Different baseline expression levels in healthy pediatric vs adult samples. Conclusions: Within months of pediatric AD onset, systemic immune activation is present, with Th2/Th17 skewing but otherwise different proteomic patterns from adult AD. Future correlation of proteomic patterns with disease course, comorbidity development, and drug response may yield predictive biomarkers.

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