Early immunological changes in atopic dermatitis, and monitoring of disease

Abstract

While new and more specific treatments for atopic dermatitis (AD) are much needed, studying this multifactorial disease remains a challenge. Mouse models generally only model one aspect of the disease, and results may not be reproducible in humans. Using biopsies from inflamed human AD skin usually misses the early immunological changes that occur when an eczema lesion develops. In the atopy patch test (APT), an allergen such as house dust mite (HDM) is applied onto the human nonlesional AD skin, which results in an eczema lesion in approximately half of the sensitized AD patients. This thesis further substantiates the evidence for the APT reaction as a relevant model for studying the early immunological changes in human AD lesions. Gene expression patterns in APT reactions overlapped markedly with those in lesional AD skin with respect to among others: T helper cell polarization, epidermal differentiation protein, antimicrobial peptide and protease-activity-related gene expression. Furthermore, in contrast to an often used vitamin D3-induced eczema mouse model, vitamin D3-stimulation did not induce TSLP expression in primate and human (nonlesional AD) skin. The observed difference between mice and (non)human primates may result from species-specific variations in the TSLP promotor. This illustrates that findings in mouse models cannot easily be extrapolated to humans. Lastly, in this thesis the application of the levels of thymus and activation-regulated chemokine (TARC) in serum as an objective tool for monitoring AD severity in the daily practice setting is investigated. In a large daily practice AD patient population, the correlation between serum TARC and AD severity score is moderate. Serum TARC levels and AD severity scores change congruently during follow-up in the majority of AD patients. Consecutive sTARC measurements are therefore considered a useful tool for monitoring AD severity in daily practice.