Defining the skin and blood biomarkers of pediatric atopic dermatitis

Project: Research project

Project Details

Description

Atopic dermatitis (AD), or atopic eczema, is the most common inflammatory skin disorder. Its prevalence has increased during the past few decades, and AD now affects 20% of children and up to 3% of adults. Individuals with AD not infrequently have asthma and/or allergic rhinitis, and these three disorders constitute the “atopic triad”. AD onset is during the first 5 years of life in more than 85% of individuals, and when encountered in adults, the disease has generally been present for decades. The pathogenesis of AD is still elusive, but has been linked to both epidermal barrier abnormalities and immune defects, with activation of distinct T-cell subsets as a Th2/Th22 polarized disease. We and others have demonstrated important roles of both barrier abnormalities and immune activation in disease pathogenesis, based on studies performed primarily in adult AD patients with long-term disease; the primary cause remains unclear. The factors that initiate and sustain the disease in the pediatric population have received virtually no attention, despite the predominance in pre-school children. Our recent studies have shown a marked down-regulation of epidermal differentiation proteins in both lesional and non-lesional adult skin, but significant increases of immune mediators and the epidermal differentiation complex (EDC) cluster-encoded S100As only in lesional AD skin. Our working hypothesis of disease pathogenesis in adults is that antigen penetration through barrier-disrupted skin preferentially activates Th2 and Th22 T-cells with subsequent effects of immune-derived cytokines on epidermal structure and function. Studies to define biomarkers of disease activity are guiding the development and clinical testing of targeted therapies for AD, but our understanding of biomarkers is incomplete, especially in affected children.

In the proposed studies, we will ask the following questions:
a. What are the cutaneous biomarkers in early AD in children and how do these compare with disease activity, epidermal barrier function, and known biomarkers in adult AD skin?
b. Are there useful biomarkers in the blood of children with AD that compare well with skin immune and barrier biomarkers, and could enable a less invasive means to follow biomarker changes and direct therapy than skin biopsy?
StatusFinished
Effective start/end date7/1/136/30/16

Funding

  • LEO Foundation (Agmt Signed 9/9/13)

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