An Integrated Model of Atopic Dermatitis Biomarkers Highlights the Systemic Nature of the Disease

Abstract

Current atopic dermatitis (AD) models link epidermal abnormalities in lesional skin to cytokine activation. However, there is evolving evidence of systemic immune activation and detectable abnormalities in nonlesional skin. Because some of the best single correlations with severity (Scoring of AD, or SCORAD) are detected not only in lesional but also nonlesional skin and blood, more complex biomarker models of AD are needed. We thus performed extensive biomarker measures in these compartments using univariate and multivariate approaches to correlate disease biomarkers with SCORAD and with a combined hyperplasia score [thickness and keratin 16 (K16) mRNA] at baseline and after cyclosporine A treatment in 25 moderate to severe AD patients. Increases in serum cytokines and chemokines (IL-13, IL-22, CCL17) were found in AD versus healthy individuals and were reduced with treatment. SCORAD correlated with immune (IL-13, IL-22) and epidermal (thickness, K16) measures in lesional and, even more strongly, in nonlesional AD. Serum cytokines also had higher correlations with nonlesional markers at baseline and with treatment. Multivariate U statistics improved baseline and treatment-response SCORAD correlations. Nonlesional models showed the strongest correlations, with further improvement upon integration of serum markers. Even better correlations were obtained between biomarkers and the hyperplasia score. Larger cohorts are needed to confirm these preliminary data.

Atopic dermatitis phenotypes and the need for personalized medicine

“…However because of the heterogeneous nature of atopic dermatitis, the establishment of such correlations is complex. A recent study has suggested that the integration of biomarkers from lesional and nonlesional atopic dermatitis skin together to blood biomarkers gave the best correlation with atopic dermatitis severity measured by scoring atopic dermatitis (SCORAD) index score [9 ▪ ]. Another study found that a combination of four serum biomarkers: thymus and activation-regulated chemokine (TARC)/CC chemokine ligand 17 (CCL17), pulmonary and activation-regulated chemokine (PARC)/CC chemokine ligand 18 (CCL18), IL-22, and sIL-2R, correlated better with atopic dermatitis severity (six area six sign atopic dermatitis score) than individual biomarkers [10].…”

Diluted sodium hypochlorite (bleach) in dogs: antiseptic efficacy, local tolerability and in vitro effect on skin barrier function and inflammation

“…Chemokine ligand‐2 represents a typical NF‐κB‐dependent inflammatory gene; CCL17 is secreted by epidermal keratinocytes and plays an important role in AD of humans and dogs . The primary keratinocyte cultures were transferred into 24 well plates (Thermo Fischer Scientific) at a density of approximately 1 × 10 5 /well and subcultured until 80% confluence in maintenance medium (10% FBS).…”

Understanding the immune landscape in atopic dermatitis: The era of biologics and emerging therapeutic approaches

“…Both are characterized by cellular and molecular abnormalities, including markers of epidermal hyperplasia, cellular infiltrates and increased inflammatory mediators compared with skin from individuals without AD . The inflammatory changes evident in non‐lesional skin may reflect, in part, the systemic nature of AD …”

“…Moderate‐to‐severe AD is viewed as a systemic disease with increases in T and B cells in the circulation as well as in skin tissue . The systemic nature of the disease is also reflected in associated comorbidities, including cardiovascular, neuropsychiatric and malignant diseases, among others …”