title: The squamous cell carcinoma antigens as relevant biomarkers of atopic dermatitis.
abstract: BACKGROUND
  Although it is thought that both Th1- and Th2-type inflammations are involved in the pathogenesis of atopic dermatitis (AD), it is controversial which immune response is more involved in regulating the clinical severity of AD. We recently found that the squamous cell carcinoma antigens 1 (SCCA1) and SCCA2 are novel biomarkers of bronchial asthma, downstream of IL-4 and IL-13.
  
  
  OBJECTIVE
  We examined whether SCCA1 and SCCA2 could also serve as biomarkers of AD, reflecting its Th2-type immune responses, and whether the expression level of SCCA was correlated with clinical severity of AD.
  
  
  METHODS
  We compared the expression of SCCA1 and SCCA2 at the mRNA and protein levels in both involved and uninvolved skin of AD patients and in normal control skin. We next analysed induction of SCCA by IL-4 or IL-13 in keratinocytes. Finally, we compared the serum level of SCCA with laboratory parameters reflecting Th2-type inflammation and clinical severity in AD patients.
  
  
  RESULTS
  SCCA1 and SCCA2 were highly expressed in involved skin of AD patients, compared with their uninvolved skin, at both mRNA and protein levels. SCCA protein was dominantly expressed in suprabasal keratinocytes in the epidermis of AD patients. Either IL-4 or IL-13, but not IFN-gamma or TNF, induced production of SCCA in keratinocytes. These result suggest that SCCA is induced in AD skin, probably due to direct actions of IL-4 and/or IL-13 on keratinocytes. Serum levels of SCCA were well correlated with eosinophil numbers and serum lactate dehydrogenase levels, and weakly with serum IgE levels, in AD patients. Furthermore, serum levels of SCCA were strongly correlated with clinical severity.
  
  
  CONCLUSIONS
  Th2-type inflammation dominantly regulates the clinical severity of AD, and SCCA is a relevant biomarker of AD, reflecting both Th2-type inflammation and clinical severity.
authors.affiliation: Department of Dermatology, Atopy (Allergy) Research Center, Juntendo University, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Mitsuishi
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: Y
authors.initials: Y
authors.lastname: Sakata
authors.forename: N
authors.initials: N
authors.lastname: Yuyama
authors.forename: K
authors.initials: K
authors.lastname: Arima
authors.forename: Y
authors.initials: Y
authors.lastname: Sugita
authors.forename: H
authors.initials: H
authors.lastname: Suto
authors.forename: K
authors.initials: K
authors.lastname: Izuhara
authors.forename: H
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D000328:Adult; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D006801:Humans; D018793:Interleukin-13 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D015603:Keratinocytes / Q000276:immunology; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D012720:Severity of Illness Index; D012867:Skin / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D018793:Interleukin-13; D012333:RNA, Messenger; D015843:Serpins; C051072:squamous cell carcinoma-related antigen; D015847:Interleukin-4