Soluble E-cadherin: A marker of genital epithelial disruption

The genital epithelial barrier is a crucial first line of defence against HIV, and epithelial disruption may enhance HIV susceptibility. Assessment of genital epithelial integrity require biopsies, but their collection is not practical in many research settings. A validated biomarker of genital epithelial barrier integrity would therefore be useful. E-cadherin, an adhesion component of the cell-cell junction in epithelial tissues, may be released as soluble E-cadherin (sE-cad) upon epithelial trauma, and so we evaluated sE-cad as a marker of genital epithelial disruption. First, using an in vitro monolayer of immortalised endocervical epithelial cells, we demonstrate that sE-cad, IL-1β, and IL-1α levels are immediately increased after physical disruption, followed by a delayed increase in IL-6 levels compared to undisrupted controls. In vivo studies confirmed that sE-cad levels in cervicovaginal secretions were significantly elevated 6 hours after endocervical cytobrush sampling. Furthermore, the level of sE-cad in coronal sulcus swabs from Ugandan men was inversely correlated with the amount of membrane-bound E-cadherin within the overlying foreskin tissues. Our results validate the use of soluble E-cadherin as a marker of epithelial disruption and demonstrate that the processes of physical disruption and inflammation in the genital tract are strongly intertwined.