title: Immunomodulatory effects of etanercept on peripheral joint synovitis in the spondylarthropathies.
abstract: OBJECTIVE
  Because different tumor necrosis factor alpha (TNFalpha) blockers may have distinct immunomodulatory effects on specific disease manifestations, the present study was carried out to investigate the immunomodulating effects of etanercept on peripheral synovitis in the spondylarthropathies (SpA).
  
  
  METHODS
  Peripheral joint disease was assessed clinically, histologically, and radiologically in a prospective 2-year study of 20 patients with SpA treated with etanercept. Synovial tissue biopsy samples obtained at weeks 0, 12, and 52 were analyzed by histology and immunohistochemistry for the extent of inflammation, changes to tissue architecture, and matrix degradation. Serum levels of myeloid-related protein 8 (MRP-8)/MRP-14, matrix metalloproteinase 3 (MMP-3), and cartilage oligomeric matrix protein (COMP) were determined by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Etanercept induced a rapid and sustained clinical improvement of peripheral joint disease. Histologic synovitis was down-regulated, with a profound reduction in global cellular infiltration and T lymphocytes, but not B lymphocytes. The most prominent change in markers of inflammation was a reduction in the different macrophage subsets (CD68, CD163, MRP-8, and MRP-14), but this was not paralleled by a decrease in serum MRP-8/MRP-14. Structural changes included normalization of lining layer hyperplasia and a moderate reduction in vascularity. However, no effect on the microarchitecture of lymphoid aggregates was observed. In terms of an effect on matrix degradation, the synovial expression of MMP-3 and MMP-9 was down-modulated in correlation with a rapid and profound decrease in serum MMP-3. At week 52, serum COMP levels were also reduced. No significant radiologic disease progression was observed in these patients over a 2-year period.
  
  
  CONCLUSIONS
  Use of etanercept effectively down-modulated the immunopathologic processes of SpA synovitis, both in the short term and in the long term.
authors.affiliation: Ghent University Hospital, Ghent, Belgium.
authors.forename: Elli
authors.initials: E
authors.lastname: Kruithof
authors.forename: Leen
authors.initials: L
authors.lastname: De Rycke
authors.forename: Johannes
authors.initials: J
authors.lastname: Roth
authors.forename: Herman
authors.initials: H
authors.lastname: Mielants
authors.forename: Filip
authors.initials: F
authors.lastname: Van den Bosch
authors.forename: Filip
authors.initials: F
authors.lastname: De Keyser
authors.forename: Eric M
authors.initials: EM
authors.lastname: Veys
authors.forename: Dominique
authors.initials: D
authors.lastname: Baeten
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001842:Bone and Bones / Q000276:immunology / Q000473:pathology; D002356:Cartilage / Q000276:immunology / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D000068800:Etanercept; D005109:Extracellular Matrix / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000009:adverse effects; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects; D007719:Knee Joint / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage*; D025242:Spondylarthropathies / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology; D013585:Synovitis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D007155:Immunologic Factors; D018124:Receptors, Tumor Necrosis Factor; D000068800:Etanercept