title: Assessment of epidermal subpopulations and proliferation in healthy skin, symptomless and lesional skin of spreading psoriasis.
abstract: BACKGROUND
  The margin zone in spreading psoriatic lesions has frequently been used as a model to study the changes in epidermal proliferation, keratinization and inflammation during the transition from symptomless to lesional skin. However, the dynamics of the changes in the epidermal subpopulations-basal cells, transit amplifying cells and differentiated cells-have not been studied in the transition between symptomless and lesional skin.
  
  
  OBJECTIVE
  To quantify in a dynamic model of the margin zone in psoriasis the characteristics of these subpopulations with respect to epidermal proliferation and differentiation.
  
  
  METHODS
  From seven patients with active psoriasis, biopsies were taken from the distant uninvolved skin, outer margin, inner margin and centre of a spreading psoriatic plaque. Frozen sections were labelled immunofluorescently using direct immunofluorescence for Ki-67 and beta1 integrin and the Zenon labelling technique for keratin 6, 10 and 15. Digital photographs of the stained sections were quantitatively analysed.
  
  
  RESULTS
  In the distant uninvolved skin the expression of beta1 integrin was decreased and keratin 15 expression was lost. In this area suprabasal cells expressed beta1 integrin and in the outer margin suprabasal cells expressed Ki-67. From the outer to the inner margin of the psoriasis plaque, which coincided with the appearance of the clinical lesion, there was a significant change in the various markers. The patchy expression of keratin 6 in the inner margin became homogeneous in the centre of the psoriasis plaque and here was also coexpression of keratin 6 and keratin 10 in a single cell.
  
  
  CONCLUSIONS
  The present study provides additional evidence that the distant uninvolved skin has a prepsoriatic phenotype, which is the first step in a psoriatic cascade. The cascade between symptomless and lesional skin comprises first an abnormality in inflammation with involvement of beta1 integrin-dim cells (transit amplifying cells) subsequently eliciting an enlarged germinative compartment with increased recruitment of cycling epidermal cells and focal expression of proliferation-associated keratins, ultimately culminating in a more-or-less homogeneous epidermis with massive recruitment of cycling epidermal cells and proliferation-associated keratinization.
authors.affiliation: Department of Dermatology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, the Netherlands. j.korver@derma.umcn.nl
authors.forename: J E M
authors.initials: JE
authors.lastname: Körver
authors.forename: M W F M
authors.initials: MW
authors.lastname: van Duijnhoven
authors.forename: M C
authors.initials: MC
authors.lastname: Pasch
authors.forename: P E J
authors.initials: PE
authors.lastname: van Erp
authors.forename: P C M
authors.initials: PC
authors.lastname: van de Kerkhof
mesh_terms: D002454:Cell Differentiation; D049109:Cell Proliferation; D004817:Epidermis / Q000378:metabolism / Q000473:pathology*; D019085:Fluorescent Antibody Technique, Direct / Q000379:methods; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D019012:Integrin beta1 / Q000378:metabolism; D007633:Keratins / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D011565:Psoriasis / Q000378:metabolism / Q000473:pathology*
chemical_list: D019012:Integrin beta1; D019394:Ki-67 Antigen; D007633:Keratins