title: T cells, fibroblast-like synoviocytes, and granzyme B+ cytotoxic cells are associated with joint damage in patients with recent onset rheumatoid arthritis.
abstract: OBJECTIVE
  To determine immunohistological markers in synovial tissue of patients with early rheumatoid arthritis (RA) which are associated with unfavourable disease outcome.
  
  
  METHODS
  Synovial tissue was obtained from 36 patients with RA within 1 year after the initial symptoms and before starting disease modifying antirheumatic drug treatment. Clinical, laboratory, and radiological assessments (Larsen score) were performed at the time of the biopsy and at the end of follow up (mean 58 months, range 38-72). Immunohistological analysis was performed to detect T cells, B cells, plasma cells, fibroblast-like synoviocytes (FLS), macrophages, and granzyme B+ cytotoxic cells. The sections were evaluated by digital image analysis.
  
  
  RESULTS
  Patients were divided into two groups based upon the radiological progression per year of follow up: group I with mild progression (n = 20; Larsen <2 points/year); group II with more severe progression (n = 16; Larsen > or =2 points/year). Regression analysis with a univariate model showed that the numbers of granzyme B+ cytotoxic cells (relative risk (RR) = 12, p = 0.003), T cells (RR = 11, p = 0.013), and FLS (RR = 10, p = 0.020) discriminated between groups I and II. A multivariate model demonstrated that the numbers of T cells (RR = 1.2, p = 0.015) and FLS (RR = 1.4, p = 0.013) were independent discriminators between groups I and II.
  
  
  CONCLUSIONS
  The numbers of granzyme B+ cytotoxic cells, T cells, and FLS in synovial tissue of patients with RA are related to the severity of joint damage. The data suggest a pathogenetic role for these cells in the process of joint damage.
authors.affiliation: Division of Clinical Immunology and Rheumatology, Department of Internal Medicine, University of Amsterdam/Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: M C
authors.initials: MC
authors.lastname: Kraan
authors.forename: J J
authors.initials: JJ
authors.lastname: Haringman
authors.forename: H
authors.initials: H
authors.lastname: Weedon
authors.forename: E C
authors.initials: EC
authors.lastname: Barg
authors.forename: M D
authors.initials: MD
authors.lastname: Smith
authors.forename: M J
authors.initials: MJ
authors.lastname: Ahern
authors.forename: T J M
authors.initials: TJ
authors.lastname: Smeets
authors.forename: F C
authors.initials: FC
authors.lastname: Breedveld
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 / Q000473:pathology*; D001402:B-Lymphocytes / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D053804:Granzymes; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D012697:Serine Endopeptidases / Q000378:metabolism; D013583:Synovial Membrane / Q000473:pathology*; D013601:T-Lymphocytes / Q000473:pathology*
chemical_list: C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases