Soluble E-cadherin: A marker of genital epithelial disruption.

Abstract

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 requires biopsies, but their collection is not practical in many research settings. A validated biomarker of genital epithelial barrier integrity would therefore be useful. The purpose of this study was to evaluate soluble E-cadherin (sE-cad) as a marker of genital epithelial disruption. Using in vitro models of endocervical and foreskin epithelial cells, we assessed changes in sE-cad, IL-6, IL-1β, and IL-1α levels following mechanical disruption. We also assessed changes in sE-cad levels in vivo in cervicovaginal secretions after epithelial disruption by endocervical cytobrush sampling in Canadian women, and assessed the relationship between levels of sE-cad in coronal sulcus swabs to membrane-bound E-cadherin in the overlying foreskin tissue in Ugandan men. sE-cad levels immediately increased after in vitro epithelial physical disruption with the degree of elevation dependent on the extent of disruption, as did levels of IL-1β and IL-1α; this was followed by a delayed increase in IL-6 levels. In vivo results confirmed that sE-cad levels in cervicovaginal secretions were elevated 6h after cytobrush sampling when compared to baseline. Furthermore, levels of sE-cad in the prepuce were inversely correlated with the amount of membrane-bound E-cadherin of overlying tissue. Our results validate the use of sE-cad as a marker of epithelial disruption and demonstrate that the processes of physical disruption and inflammation in the genital tract are strongly intertwined.