title: Identification of interleukin-7 as a candidate disease mediator in spondylarthritis.
abstract: OBJECTIVE
  Understanding of the molecular pathophysiology of spondylarthritis (SpA) remains largely elusive. This is related both to the complexity of the disease (axial versus peripheral disease, inflammation versus tissue remodeling) and to the difficulty in obtaining samples from primary disease sites. This study was undertaken to explore a gene expression approach for identifying novel candidate mediators of SpA.
  
  
  METHODS
  Sacroiliac joint fluid aspirates from 3 SpA patients with active sacroiliitis were studied by microarray analysis. The expression of selected candidate molecules in peripheral synovitis was confirmed by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Microarray analysis identified 4 sacroiliitis gene clusters, containing a total of 47 messenger RNA (mRNA) transcripts. Two clusters contained genes expressed in all sacroiliitis samples, corresponding to both known and unsuspected candidate mediators of SpA pathology. These included proinflammatory molecules as well as molecules involved in tissue remodeling, such as transforming growth factor beta2. Of the novel candidate genes selected for confirmation, interleukin-7 (IL-7) mRNA expression was higher in SpA peripheral synovial fluid and synovial tissue samples than in osteoarthritis samples, and similar to expression in rheumatoid arthritis (RA) samples. At the protein level, synovial fluid IL-7 levels were even higher in SpA than in RA, despite lower levels of tumor necrosis factor alpha and IL-1beta.
  
  
  CONCLUSIONS
  In the present study, both known and unsuspected candidate mediators of SpA pathogenesis were identified, including IL-7. The specific overexpression of IL-7 at sites of peripheral synovitis in SpA suggests that further functional investigations of the role of this cytokine in SpA pathogenesis are warranted.
authors.affiliation: Hannover Medical School, Hannover, Germany. Rihl.Markus@MH-Hannover.de
authors.forename: Markus
authors.initials: M
authors.lastname: Rihl
authors.forename: Herbert
authors.initials: H
authors.lastname: Kellner
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kellner
authors.forename: Christian
authors.initials: C
authors.lastname: Barthel
authors.forename: David T Y
authors.initials: DT
authors.lastname: Yu
authors.forename: Paul P
authors.initials: PP
authors.lastname: Tak
authors.forename: Henning
authors.initials: H
authors.lastname: Zeidler
authors.forename: Dominique
authors.initials: D
authors.lastname: Baeten
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D006801:Humans; D015851:Interleukin-7 / Q000235:genetics / Q000502:physiology*; D008297:Male; D046228:Microarray Analysis; D005810:Multigene Family; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025241:Spondylarthritis / Q000209:etiology* / Q000235:genetics; D013585:Synovitis / Q000235:genetics
chemical_list: D015851:Interleukin-7; D012333:RNA, Messenger