title: Gene Expression Profiling in Peripheral Blood Cells and Synovial Membranes of Patients with Psoriatic Arthritis.
abstract: BACKGROUND
  Psoriatic arthritis (PsA) is an inflammatory arthritis whose pathogenesis is poorly understood; it is characterized by bone erosions and new bone formation. The diagnosis of PsA is mainly clinical and diagnostic biomarkers are not yet available. The aim of this work was to clarify some aspects of the disease pathogenesis and to identify specific gene signatures in paired peripheral blood cells (PBC) and synovial biopsies of patients with PsA. Moreover, we tried to identify biomarkers that can be used in clinical practice.
  
  
  METHODS
  PBC and synovial biopsies of 10 patients with PsA were used to study gene expression using Affymetrix arrays. The expression values were validated by Q-PCR, FACS analysis and by the detection of soluble mediators.
  
  
  RESULTS
  Synovial biopsies of patients showed a modulation of approximately 200 genes when compared to the biopsies of healthy donors. Among the differentially expressed genes we observed the upregulation of Th17 related genes and of type I interferon (IFN) inducible genes. FACS analysis confirmed the Th17 polarization. Moreover, the synovial trascriptome shows gene clusters (bone remodeling, angiogenesis and inflammation) involved in the pathogenesis of PsA. Interestingly 90 genes are modulated in both compartments (PBC and synovium) suggesting that signature pathways in PBC mirror those of the inflamed synovium. Finally the osteoactivin gene was upregulared in both PBC and synovial biopsies and this finding was confirmed by the detection of high levels of osteoactivin in PsA sera but not in other inflammatory arthritides.
  
  
  CONCLUSIONS
  We describe the first analysis of the trancriptome in paired synovial tissue and PBC of patients with PsA. This study strengthens the hypothesis that PsA is of autoimmune origin since the coactivity of IFN and Th17 pathways is typical of autoimmunity. Finally these findings have allowed the identification of a possible disease biomarker, osteoactivin, easily detectable in PsA serum.
authors.affiliation: Institute G. Gaslini, Genova, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Dolcino
authors.affiliation: University of Genova, Genova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ottria
authors.affiliation: University of Verona, Verona, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Barbieri
authors.affiliation: University of Verona, Verona, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Patuzzo
authors.affiliation: University of Verona, Verona, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Tinazzi
authors.affiliation: University of Verona, Verona, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Argentino
authors.affiliation: University of Verona, Verona, Italy.
authors.forename: Ruggero
authors.initials: R
authors.lastname: Beri
authors.affiliation: University of Verona, Verona, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Lunardi
authors.affiliation: Institute G. Gaslini, Genova, Italy; University of Genova, Genova, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Puccetti
mesh_terms: D000328:Adult; D015535:Arthritis, Psoriatic / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D013583:Synovial Membrane / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D015415:Biomarkers