Time-course profiling of serine protease activities and inflammatory profiles in netherton syndrome and atopic dermatitis via tape-stripping

Summary: Abstract Body: Netherton syndrome (NS) is a rare autosomal recessive skin disorder with ichthyosis, hair abnormalities, and atopic predisposition. It results from SPINK5 mutations, causing LEKTI deficiency. We investigated time-course changes in serine protease activities and cytokine profiles in NS by evaluating a 19-year-old patient with compound heterozygous SPINK5 mutations. Clinical severity was assessed using the Ichthyosis Area and Severity Index (IASI). Tape-stripped scales were analyzed for protease activity and RNA sequencing during erythroderma (IASI=44.4) and stable phases (IASI=18.2). Trypsin-like serine protease activity was persistently elevated compared to atopic dermatitis (AD) patients and healthy controls, independent of skin condition. Chymotrypsin-like activity was also elevated but less dramatically. RNA sequencing revealed increased expression of inflammatory cytokines, including IL-1α, IL-1β, IL-18, IL-36α, IL-36γ, and IL-17C during erythroderma. Additionally, in a separate case series of 5 AD patients, tape-stripping was used to measure serine protease activities before and after treatment with an oral JAK1 inhibitor. Chymotrypsin-like serine protease activity significantly decreased within 2-4 weeks of treatment initiation compared to baseline. These results suggest that serine protease activity in NS is not regulated by inflammation, and that chymotrypsin activity in AD is controlled by inflammation. Our study indicates that serine protease activity is a therapeutic target for patients with NS, and further detailed investigations are needed. Ko Sunagawa¹, Anri Morita¹, Shin Morizane¹ 1. Dermatology, Okayama Daigaku, Okayama, Okayama Prefecture, Japan. Epidermal Structure and Barrier Function