Immunological phenotype and skin modeling of Netherton syndrome.

Netherton syndrome (NTS) is a syndromic ichthyosis characterized by scaling, erythroderma, and proneness towards allergies and infections. It is caused by mutations in the SPINK5 gene, encoding the lympho-epithelial Kazal-type 5 related inhibitor (LEKTI), which regulates the activity of kallikreins in the skin. Treatment options are limited, insufficient, time-consuming and a financial burden for the patients. In the last years, genotype-phenotype correlations in NTS and immunological phenotypes have been delineated. Psoriasiform patterns have been described. Moreover, the literature reports on biological therapies as novel therapeutic options in NTS. Previously, recombinant human LEKTI domain 8+9 (rhLEKTI 8+9) was identified as a potent kallikrein inhibitor, implying that these subunits are suitable for a topical protein substitution therapy. We aimed to characterize NTS in more detail to discuss further personalized therapeutic options by phenotyping a large cohort of NTS patients and performing serum analyses. Moreover, we worked on preliminary steps for a protein replacement therapy by investigating recombinant expressed rhLEKTI8+9 and establishing 3D epidermal equivalents for therapeutic evaluation.