Netherton syndrome is a rare autosomal recessive disorder characterized by a broad skin phenotype. It is characterized by severe ichthyosis, specific hair shafts (“bamboo hair”) and atopic skin manifestations with high levels of IgE. The syndrome leads to high postnatal mortality and adult patients present atopic-dermatitis symptoms with scaling and erythroderma. Severity of the phenotypes is correlated to protease hyperactivity and inversely correlated with LEKTI activity.
The genetic origin of Netherton syndrome lies in mutations of the kallikrein inhibitor LEKTI leading to a non-functional inhibitor. Significant high levels of KLKs were found in the stratum corneum and serum of NS patients.
Atopic dermatitis is a chronic inflammatory disease associated with changes in stratum corneum function and structure. Like Netherton syndrome, atopic dermatitis presents skin features such as scales, ichthyosis, and erythroderma. High IgE levels are also found in atopic dermatitis patients. SPINK5/LEKTI polymorphisms have also been associated with the disease. Moreover increased expression of skin kallikreins in the stratum corneum and serum has been found in patients with atopic dermatitis. Atopic skin presented elevated expression of KLK7 in the stratum corneum and LEKTI localization deeper in the stratum corneum with no co-localization suggesting an imbalance which leads to the unregulated desquamation seen in such disease.
These data suggest common mechanisms in atopic dermatitis and Netherton syndrome and emphasizes the role of controlled serine protease activity in maintenance of skin barrier integrity.
Psoriasis is a chronic autoimmune disease. At the cellular level, psoriasis is characterized by epidermal inflammation, hyperplasia, abnormal keratinocyte differentiation, and chronic neutrophil and T-cell infiltrates. Aberrant levels of skin kallikreins were found in the stratum corneum and serum of patients with psoriasis, suggesting their involvement in the disease. Aberrant kallikrein expression was shown to be dependent on phenotype, severity and therapy of psoriasis.