BIOMARKERS OF ATOPIC DERMATITIS IN THE UMBILICAL CORD

Abstract

Mechanisms driving atopic dermatitis (AD) in infancy are complex and poorly understood. Ethically, epidermal biopsies of infants are difficult to obtain. The aim of this study was to investigate whether the umbilical cord (UC) which has histological similarities with the differentiated epidermis, could substitute epidermal biopsies as a surrogate non-invasive tissue source of early predictive biomarkers of AD. Using UCs (n=497) obtained from the Growing Up in Singapore Toward healthy Outcomes cohort, immunoblotting (n=42) and filaggrin DNA sequencing (n=455) were done to determine whether differential epidermal and AD-related protein expression in UCs or filaggrin loss-of-function mutations could be predictive of AD development later in life. Loricrin (p=0.010), GATA-3 (p=0.008) and kallikrien-7 (p=0.015) were found to be significantly differentially expressed. Filaggrin loss-of-function mutations were found to be associated with AD persistence (p=0.012). The five-protein predictive biomarker index (risk-score model) was the best in discriminating those who developed AD (AUROC =0.880). To conclude, the UC is a tissue source rich in protein and genetic biomarkers of AD. Clinically relevant early protein and genetic biomarkers from the UC would allow infants at-risk of AD to be identified and enrolled early into trials to prevent AD development.