title: Comparative genomic profiling of synovium versus skin lesions in psoriatic arthritis.
abstract: OBJECTIVE
  To our knowledge, there is no broad genomic analysis comparing skin and synovium in psoriatic arthritis (PsA). Also, there is little understanding of the relative levels of cytokines and chemokines in skin and synovium. The purpose of this study was to better define inflammatory pathways in paired lesional skin and affected synovial tissue in patients with PsA.
  
  
  METHODS
  We conducted a comprehensive analysis of cytokine and chemokine activation and genes representative of the inflammatory processes in PsA. Paired PsA synovial tissue and skin samples were obtained from 12 patients on the same day. Gene expression studies were performed using Affymetrix HGU133 Plus 2.0 arrays. Confirmatory quantitative real-time polymerase chain reaction (PCR) was performed on selected transcripts. Cell populations were assessed by immunohistochemistry and immunofluorescence.
  
  
  RESULTS
  Globally, gene expression in PsA synovium was more closely related to gene expression in PsA skin than to gene expression in synovium in other forms of arthritis. However, PsA gene expression patterns in skin and synovium were clearly distinct, showing a stronger interleukin-17 (IL-17) gene signature in skin than in synovium and more equivalent tumor necrosis factor (TNF) and interferon-γ gene signatures in both tissues. These results were confirmed with real-time PCR.
  
  
  CONCLUSIONS
  This is the first comprehensive molecular comparison of paired lesional skin and affected synovial tissue samples in PsA. Our results support clinical trial data showing that PsA skin and joint disease are similarly responsive to TNF antagonists, while IL-17 antagonists have better results in PsA skin than in PsA joints. Genes selectively expressed in PsA synovium might direct future therapies for PsA.
authors.affiliation: The Rockefeller University, New York, New York.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Belasco
authors.forename: James S
authors.initials: JS
authors.lastname: Louie
authors.forename: Nicholas
authors.initials: N
authors.lastname: Gulati
authors.forename: Nathan
authors.initials: N
authors.lastname: Wei
authors.forename: Kristine
authors.initials: K
authors.lastname: Nograles
authors.forename: Judilyn
authors.initials: J
authors.lastname: Fuentes-Duculan
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mitsui
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
mesh_terms: D015535:Arthritis, Psoriatic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018925:Chemokines / Q000235:genetics* / Q000378:metabolism; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology
chemical_list: D018925:Chemokines; D016207:Cytokines