The hand eczema proteome: imbalance of epidermal barrier proteins.

BACKGROUND: Chronic hand eczema (CHE) is a common skin disease with a high socioeconomic impact. While some light has been shed on the genetic factors that predispose individuals to the disease, little is known about its actual pathogenesis. OBJECTIVES: We aimed to carry out a systematic and comprehensive analysis of the differential protein expression in CHE using modern mass spectrometry. METHODS: We performed liquid chromatography with tandem mass spectrometry analyses and label-free quantification to analyse the proteomic profile of palmar skin from 12 individuals (six patients with hand eczema and six healthy volunteers). Immunohistochemistry of the palmar skin from seven different patients with hand eczema and seven different healthy volunteers was performed in a second step. RESULTS: With this method we were able to identify 185 candidate proteins with a significantly different abundance in the hand eczema samples. Among them we found several barrier proteins: filaggrin (FLG), FLG-2 and hornerin were all downregulated in the hand eczema samples, as were the desquamation-related enzymes kallikrein-related peptidase (KLK)5 and KLK7 and cystatin E/M. The antimicrobial peptides S100A7 and S100A8/A9 and the small proline-rich protein 2B and S100A11 were upregulated in the diseased skin. Immunohistochemistry confirmed these findings. CONCLUSIONS: Our results corroborate the assumption that skin barrier dysfunction plays an essential role in the pathogenesis of CHE.