title: Interleukin-17-positive mast cells contribute to synovial inflammation in spondylarthritis.
abstract: OBJECTIVE
  Studies comparing spondylarthritis (SpA) to rheumatoid arthritis (RA) synovitis suggest that innate immune cells may play a predominant role in the pathogenesis of SpA. Recent observations have indicated a marked synovial mast cell infiltration in psoriatic SpA. We therefore undertook the present study to investigate the potential contribution of mast cells to synovial inflammation in SpA.
  
  
  METHODS
  Synovial tissue and fluid were obtained from patients with either nonpsoriatic or psoriatic SpA (n=82) and patients with RA (n=50). Synovial biopsy tissue was analyzed by immunostaining and used in ex vivo cultures. Synovial fluid was analyzed by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  We observed a strong and specific increase of c-Kit-positive mast cells in the synovium from patients with SpA compared to the synovium from patients with RA synovitis, which was independent of disease subtype (nonpsoriatic versus psoriatic), disease duration, and treatment. Staining of mast cell granules, analysis of synovial fluid, and results in ex vivo tissue culture did not indicate increased degranulation in SpA synovitis. However, mast cells expressed significantly more interleukin-17 (IL-17) in SpA than in RA synovitis, and mast cells constituted the major IL-17-expressing cell population in the SpA synovium. Ex vivo targeting of synovial mast cells with the c-Kit inhibitor imatinib mesylate significantly decreased the production of IL-17 as well as other proinflammatory cytokines in synovial tissue cultures. Analysis of paired pre- and posttreatment synovial tissue samples indicated that the mast cell/IL-17 axis in SpA was not modulated by effective tumor necrosis factor (TNF) blockade.
  
  
  CONCLUSIONS
  The specific and TNF-independent increase in IL-17-expressing mast cells may contribute to the progression of synovial inflammation in peripheral SpA.
authors.affiliation: Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Troy
authors.initials: T
authors.lastname: Noordenbos
authors.forename: Nataliya
authors.initials: N
authors.lastname: Yeremenko
authors.forename: Ioana
authors.initials: I
authors.lastname: Gofita
authors.forename: Marleen
authors.initials: M
authors.lastname: van de Sande
authors.forename: Paul P
authors.initials: PP
authors.lastname: Tak
authors.forename: Juan D
authors.initials: JD
authors.lastname: Caňete
authors.forename: Dominique
authors.initials: D
authors.lastname: Baeten
mesh_terms: D000328:Adult; D000368:Aged; D015535:Arthritis, Psoriatic / Q000378:metabolism / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology*; D001549:Benzamides; D015550:Cell Degranulation / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D006801:Humans; D000068877:Imatinib Mesylate; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D025241:Spondylarthritis / Q000378:metabolism / Q000473:pathology*; D013582:Synovial Fluid / Q000737:chemistry / Q000378:metabolism; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013585:Synovitis / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: D001549:Benzamides; D020381:Interleukin-17; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit