title: Insights in to the pathogenesis of axial spondyloarthropathy based on gene expression profiles.
abstract: BACKGROUND
  Axial spondyloarthropathy (SpA) is a group of inflammatory diseases, with ankylosing spondylitis as the prototype. SpA affects the axial skeleton, entheses, joints and, at times, the eyes. This study tested the hypothesis that SpA is characterized by a distinct pattern of gene expression in peripheral blood of affected individuals compared with healthy controls.
  
  
  METHODS
  High-density, human GeneChip probe arrays were used to profile mRNA of peripheral blood cells from 18 subjects with SpA and 25 normal individuals. Samples were processed as two separate sets at different times (11 SpA + 12 control subjects in primary set (Set 1); 7 SpA+ 13 control subjects in the validation set (Set 2)). Blood samples were taken at a time when patients were not receiving systemic immunomodulatory therapy. Differential expression was defined as a 1.5-fold change with a q value < 5%. Gene ontology and pathway information were also studied.
  
  
  RESULTS
  Signals from 134 probe sets (representing 95 known and 12 unknown gene transcripts) were consistently different from controls in both Sets 1 and 2. Included among these were transcripts for a group of 20 genes, such as interleukin-1 (IL-1) receptors 1 and 2, Nod-like receptor family, pyrin domain containing 2 (NLRP2), secretory leukocyte peptidase inhibitor (SLPI), secreted protein acidic and rich in cysteine (SPARC), and triggering receptor expressed on myeloid cells 1 (TREM-1) that are clearly related to the immune or inflammatory response and a group of 4 transcripts that have a strong role in bone remodeling.
  
  
  CONCLUSIONS
  Our observations are the first to implicate SPARC, SLPI, and NLRP2, a component of the innate immune system, in the pathogenesis of SpA. Our results also indicate a possible role for IL-1 and its receptors in SpA. In accord with the bone pathology component of SpA, we also found that expression levels of transcripts reflecting bone remodeling factors are also distinguishable in peripheral blood from patients with SpA versus controls. These results confirm some previously identified biomarkers implicated in the pathogenesis of SpA and also point to novel mediators in this disease.
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon, 97239, USA. s_m_sharma@yahoo.com
authors.forename: Srilakshmi M
authors.initials: SM
authors.lastname: Sharma
authors.forename: Dongseok
authors.initials: D
authors.lastname: Choi
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Planck
authors.forename: Christina A
authors.initials: CA
authors.lastname: Harrington
authors.forename: Carrie R
authors.initials: CR
authors.lastname: Austin
authors.forename: Jinnell A
authors.initials: JA
authors.lastname: Lewis
authors.forename: Tessa N
authors.initials: TN
authors.lastname: Diebel
authors.forename: Tammy M
authors.initials: TM
authors.lastname: Martin
authors.forename: Justine R
authors.initials: JR
authors.lastname: Smith
authors.forename: James T
authors.initials: JT
authors.lastname: Rosenbaum
mesh_terms: D000328:Adult; D001798:Blood Proteins / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D020411:Oligonucleotide Array Sequence Analysis; D015676:Osteonectin / Q000235:genetics*; D025242:Spondylarthropathies / Q000235:genetics*
chemical_list: D001798:Blood Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015676:Osteonectin; C117201:STOML1 protein, human; C406287:STOML2 protein, human