Development of a back-titration assay to quantitate functional lympho-epithelial Kazal-type inhibitors (LEKTI) in skin samples

Abstract

The lympho-epithelial Kazal-type inhibitors (LEKTI) are key to control skin turnover, and their absence causes Netherton syndrome. For clinical sample testing of LEKTI-based therapies, a robust analytical method to measure LEKTI-like activity in skin is required. This work reports on the development of a back-titration method to determine incremental LEKTI-like activity in skin samples. The method meets the analytical requirements for study sample testing, and reliable quantification can be achieved with negligible skin matrix interference. This assay does not provide analyte identity, but it can be used to measure treatment-driven increments of LEKTI-like activity within the skin epidermis.