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

J Am Acad Dermatol. 2019 Aug;81(2):510-519. doi: 10.1016/j.jaad.2019.04.036. Epub 2019 Apr 19.

Abstract

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-α). 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.

Keywords: Atopic dermatitis; Olink; infant; multiplex assay; pediatric; peripheral blood; proximity extension assay.

MeSH terms

  • Age Factors
  • Biomarkers / blood
  • Case-Control Studies
  • Chemokines / blood*
  • Child, Preschool
  • Chronic Disease
  • Dermatitis, Atopic / blood*
  • Dermatitis, Atopic / metabolism
  • E-Selectin / blood
  • Elafin / blood*
  • Fatty Acid-Binding Proteins / blood
  • Female
  • Fibroblast Growth Factors / blood
  • Humans
  • Infant
  • Inflammation / blood*
  • Interleukin-2 Receptor alpha Subunit / blood
  • Male
  • Matrix Metalloproteinases / blood*
  • Peroxidase / blood
  • Proteome / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Interleukin / blood*
  • Severity of Illness Index
  • Transforming Growth Factor alpha / blood

Substances

  • Biomarkers
  • Chemokines
  • E-Selectin
  • Elafin
  • FABP4 protein, human
  • Fatty Acid-Binding Proteins
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • PI3 protein, human
  • Proteome
  • RNA, Messenger
  • Receptors, Interleukin
  • Transforming Growth Factor alpha
  • fibroblast growth factor 21
  • Fibroblast Growth Factors
  • Peroxidase
  • Matrix Metalloproteinases