title: Treatment-induced remission in rheumatoid arthritis patients is characterized by a reduction in macrophage content of synovial biopsies.
abstract: OBJECTIVE
  To document the change in synovial membrane macrophage and T-lymphocyte content in rheumatoid arthritis (RA) patients who achieve remission induced by disease-modifying anti-rheumatic drugs (DMARDs).
  
  
  METHODS
  Arthroscopic synovial biopsies were taken from four to seven sites around a knee joint in 13 patients with RA before and at regular intervals after commencing treatment with a DMARD. The cellular content of synovial membrane biopsies taken at regular intervals for a period of up to 3 yr after commencing treatment was quantitated by routine histopathology and immunohistochemical labelling with anti-macrophage (CD68) and anti-T lymphocyte (UCHL-1) antibodies. Synovial biopsies were quantitated with a validated semiquantitative scoring system and video image analysis.
  
  
  RESULTS
  Nine patients obtained clinical remission, as defined by American College of Rheumatology (ACR) criteria. The changes that occurred in the synovial biopsies included a reduction in lining layer thickness, reduced vascularity and cellular infiltrate. The most significant reduction in cellular infiltrate was in the lining layer macrophages, with less dramatic change in the subintimal macrophage infiltrate. Although there was a reduction in CD45 Ro-positive T lymphocytes in the synovial membranes of patients who attained ACR-defined disease remission, it was less significant than the reduction in macrophage content of the synovial membranes and tended to plateau at a reduced level of T-cell infiltration.
  
  
  CONCLUSIONS
  Remission in RA patients is characterized by a predominant reduction in macrophage content of the synovial membrane, suggesting that current DMARDs may target this cell and its inflammatory mediators.
authors: Department of Medicine, Flinders Medical Centre, Adelaide, South Australia.
authors: M D
authors: MD
authors: Smith
authors: M C
authors: MC
authors: Kraan
authors: J
authors: J
authors: Slavotinek
authors: V
authors: V
authors: Au
authors: H
authors: H
authors: Weedon
authors: A
authors: A
authors: Parker
authors: M
authors: M
authors: Coleman
authors: P J
authors: PJ
authors: Roberts-Thomson
authors: M J
authors: MJ
authors: Ahern
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology; D001706:Biopsy; D005260:Female; D006801:Humans; D008264:Macrophages / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D013583:Synovial Membrane / Q000473:pathology*
chemical_list: D018501:Antirheumatic Agents