title: The hand eczema proteome: imbalance of epidermal barrier proteins.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Dermatology and Allergy, Ludwig Maximilian University, D-80337, Munich, Germany; Research Unit Protein Science, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Molin
authors.forename: J
authors.initials: J
authors.lastname: Merl
authors.forename: K A
authors.initials: KA
authors.lastname: Dietrich
authors.forename: M
authors.initials: M
authors.lastname: Regauer
authors.forename: M
authors.initials: M
authors.lastname: Flaig
authors.forename: V
authors.initials: V
authors.lastname: Letulé
authors.forename: T
authors.initials: T
authors.lastname: Saucke
authors.forename: T
authors.initials: T
authors.lastname: Herzinger
authors.forename: T
authors.initials: T
authors.lastname: Ruzicka
authors.forename: S M
authors.initials: SM
authors.lastname: Hauck
mesh_terms: D000328:Adult; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D002908:Chronic Disease; D055233:Cornified Envelope Proline-Rich Proteins / Q000378:metabolism; D015891:Cystatins / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D004485:Eczema / Q000209:etiology*; D004817:Epidermis / Q000378:metabolism; D005260:Female; D000091344:Filaggrin Proteins; D006229:Hand Dermatoses / Q000209:etiology*; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D007610:Kallikreins / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D020543:Proteome / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
chemical_list: D002135:Calcium-Binding Proteins; D055233:Cornified Envelope Proline-Rich Proteins; D015891:Cystatins; C000717249:FLG protein, human; C000717250:FLG2 protein, human; D000091344:Filaggrin Proteins; C503908:HRNR protein, human; D007381:Intermediate Filament Proteins; D020543:Proteome; D009418:S100 Proteins; C400147:KLK5 protein, human; C082472:KLK7 protein, human; D007610:Kallikreins