title: Association of CD163+ macrophages and local production of soluble CD163 with decreased lymphocyte activation in spondylarthropathy synovitis.
abstract: OBJECTIVE
  Since CD163+ macrophages are selectively increased in spondylarthropathy (SpA) synovitis, we investigated the role of CD163+ macrophages in synovial inflammation.
  
  
  METHODS
  Synovial biopsy samples from 26 SpA and 23 rheumatoid arthritis (RA) patients were analyzed for macrophage and lymphocyte subsets. Synovial fluid (SF) samples were analyzed by Western blotting and enzyme-linked immunosorbent assay for soluble CD163 (sCD163) and by flow cytometry for lymphocyte activation. We also analyzed sCD163 in sera from 100 SpA patients, 23 RA patients, 20 healthy controls, and 20 SpA patients treated with infliximab. Polymorphism of haptoglobin (Hp), the CD163 ligand, was determined in 130 SpA and 23 RA patients.
  
  
  RESULTS
  CD163+ macrophages, but not CD68+ macrophages, were significantly increased in SpA versus RA synovium and in HLA-B27+ versus HLA-B27- SpA. Despite similar lymphocyte numbers, activated lymphocytes (CD69+) were significantly decreased in SpA versus RA patients, with an inverse correlation between CD163 and CD69 levels. Local production of sCD163 was evidenced by a 5-7-fold higher level of sCD163 in SF than in serum and by the correlation with synovial lining CD163+ macrophages in SpA. SF sCD163 levels correlated directly with global inflammation but correlated inversely with CD69+ SF T lymphocytes in the synovium. In contrast, serum sCD163 levels were only moderately increased, did not correlate with SF sCD163 levels or parameters of inflammation, and were unaffected by infliximab therapy. The distribution of Hp polymorphism was not altered in SpA and was not related to CD163 expression.
  
  
  CONCLUSIONS
  Increased numbers of CD163+ macrophages in SpA synovium and local production of sCD163 are associated with global inflammation as well as impairment of T cell activation, suggesting a dual role for CD163+ macrophages in SpA synovitis.
authors.affiliation: Department of Rheumatology, 0K12IB, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium. dominique.baeten@ugent.be
authors.forename: Dominique
authors.initials: D
authors.lastname: Baeten
authors.forename: Holger Jon
authors.initials: HJ
authors.lastname: Møller
authors.forename: Joris
authors.initials: J
authors.lastname: Delanghe
authors.forename: Eric M
authors.initials: EM
authors.lastname: Veys
authors.forename: Søren K
authors.initials: SK
authors.lastname: Moestrup
authors.forename: Filip
authors.initials: F
authors.lastname: De Keyser
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood* / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood* / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism; D005260:Female; D006242:Haptoglobins / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000097:blood* / Q000276:immunology; D012995:Solubility; D025242:Spondylarthropathies / Q000276:immunology* / Q000378:metabolism; D013582:Synovial Fluid / Q000378:metabolism; D013585:Synovitis / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D006242:Haptoglobins; D011956:Receptors, Cell Surface