title: Reversal of atopic dermatitis with narrow-band UVB phototherapy and biomarkers for therapeutic response.
abstract: BACKGROUND
  Atopic dermatitis (AD) is a common inflammatory skin disease exhibiting a predominantly T(H)2/"T22" immune activation and a defective epidermal barrier. Narrow-band UVB (NB-UVB) is considered an efficient treatment for moderate-to-severe AD. In patients with psoriasis, NB-UVB has been found to suppress T(H)1/T(H)17 polarization, with subsequent reversal of epidermal hyperplasia. The immunomodulatory effects of this treatment are largely unknown in patients with AD.
  
  
  OBJECTIVE
  We sought to evaluate the effects of NB-UVB on immune and barrier abnormalities in patients with AD, aiming to establish reversibility of disease and biomarkers of therapeutic response.
  
  
  METHODS
  Twelve patients with moderate-to-severe chronic AD received NB-UVB phototherapy 3 times weekly for up to 12 weeks. Lesional and nonlesional skin biopsy specimens were obtained before and after treatment and evaluated by using gene expression and immunohistochemistry studies.
  
  
  RESULTS
  All patients had at least a 50% reduction in SCORAD index scores with NB-UVB phototherapy. The T(H)2, T22, and T(H)1 immune pathways were suppressed, and measures of epidermal hyperplasia and differentiation normalized. The reversal of disease activity was associated with elimination of inflammatory leukocytes and T(H)2/T22- associated cytokines and chemokines and normalized expression of barrier proteins.
  
  
  CONCLUSIONS
  Our study shows that resolution of clinical disease in patients with chronic AD is accompanied by reversal of both the epidermal defects and the underlying immune activation. We have defined a set of biomarkers of disease response that associate resolved T(H)2 and T22 inflammation in patients with chronic AD with reversal of barrier pathology. By showing reversal of the AD epidermal phenotype with a broad immune-targeted therapy, our data argue against a fixed genetic phenotype.
authors.affiliation: Columbia University College of Physicians & Surgeons, New York, NY, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Tintle
authors.forename: Avner
authors.initials: A
authors.lastname: Shemer
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujita
authors.forename: Patricia
authors.initials: P
authors.lastname: Gilleaudeau
authors.forename: Mary
authors.initials: M
authors.lastname: Sullivan-Whalen
authors.forename: Leanne
authors.initials: L
authors.lastname: Johnson-Huang
authors.forename: Andrea
authors.initials: A
authors.lastname: Chiricozzi
authors.forename: Irma
authors.initials: I
authors.lastname: Cardinale
authors.forename: Shenghui
authors.initials: S
authors.lastname: Duan
authors.forename: Anne
authors.initials: A
authors.lastname: Bowcock
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
authors.forename: Emma
authors.initials: E
authors.lastname: Guttman-Yassky
mesh_terms: D000328:Adult; D015415:Biomarkers; D002908:Chronic Disease; D003876:Dermatitis, Atopic / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000628:therapy; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D016896:Treatment Outcome; D014467:Ultraviolet Therapy; D055815:Young Adult
chemical_list: D015415:Biomarkers; D015395:Histocompatibility Antigens Class I; C089395:T22 antigen