title: Analysis of the cell infiltrate and expression of matrix metalloproteinases and granzyme B in paired synovial biopsy specimens from the cartilage-pannus junction in patients with RA.
abstract: OBJECTIVE
  Examination of synovial tissue (ST) obtained at surgery because of end stage destructive rheumatoid arthritis (RA) showed that macrophages and fibroblasts are the major cell types at the cartilage-pannus junction (CPJ). This study aimed at defining the cell infiltrate and mediators of joint destruction in ST selected at arthroscopy from the CPJ in patients with RA who did not require joint surgery.
  
  
  METHODS
  Paired synovial biopsy specimens were obtained at arthroscopy from ST adjacent to the CPJ and the suprapatellar pouch from the knee joints of 17 patients with RA. Immunohistological analysis was performed using monoclonal antibodies to detect T cells, B cells, plasma cells, macrophages, fibroblast-like synoviocytes, mast cells, and granzyme B+ cytotoxic cells as well as the expression of metalloproteinase (MMP)-1, MMP-3, and MMP-13. The sections were evaluated by computer assisted image analysis and semiquantitative analysis.
  
  
  RESULTS
  The cell infiltrate comprised mainly T cells, macrophages, and plasma cells. The ST was also infiltrated by the other cell types, but at lower numbers. Expression of MMPs was abundant, especially MMP-3. The features of ST at the CPJ were generally similar to those at the suprapatellar pouch.
  
  
  CONCLUSIONS
  The synovium at the CPJ in patients with RA who did not require joint surgery exhibits, in general, the same type of cell infiltrate and expression of MMPs and granzymes as ST from the suprapatellar pouch. The pathological changes that have been described at the CPJ in patients with RA with end stage, destructive disease may well reflect the transition to a process in which macrophages, fibroblast-like synoviocytes, and other cell types become increasingly important.
authors.affiliation: Division of Clinical Immunology and Rheumatology, Academic Medical Centre, Amsterdam, The Netherlands. T.J.Smeets@amc.uva.nl
authors.forename: T J
authors.initials: TJ
authors.lastname: Smeets
authors.forename: M C
authors.initials: MC
authors.lastname: Kraan
authors.forename: S
authors.initials: S
authors.lastname: Galjaard
authors.forename: P P
authors.initials: PP
authors.lastname: Youssef
authors.forename: M D
authors.initials: MD
authors.lastname: Smith
authors.forename: P P
authors.initials: PP
authors.lastname: Tak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000276:immunology; D001706:Biopsy; D002358:Cartilage, Articular / Q000201:enzymology* / Q000276:immunology; D005260:Female; D053804:Granzymes; D006801:Humans; D007124:Immunoenzyme Techniques; D008264:Macrophages / Q000276:immunology; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D010950:Plasma Cells / Q000276:immunology; D012697:Serine Endopeptidases / Q000378:metabolism*; D013583:Synovial Membrane / Q000201:enzymology* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases; D020782:Matrix Metalloproteinases