PMID- 16329106
OWN - NLM
STAT- MEDLINE
DCOM- 20060111
LR  - 20151119
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 52
IP  - 12
DP  - 2005 Dec
TI  - Immunomodulatory effects of etanercept on peripheral joint synovitis in the 
      spondylarthropathies.
PG  - 3898-909
AB  - 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. CONCLUSION: Use of etanercept effectively 
      down-modulated the immunopathologic processes of SpA synovitis, both in the short 
      term and in the long term.
FAU - Kruithof, Elli
AU  - Kruithof E
AD  - Ghent University Hospital, Ghent, Belgium.
FAU - De Rycke, Leen
AU  - De Rycke L
FAU - Roth, Johannes
AU  - Roth J
FAU - Mielants, Herman
AU  - Mielants H
FAU - Van den Bosch, Filip
AU  - Van den Bosch F
FAU - De Keyser, Filip
AU  - De Keyser F
FAU - Veys, Eric M
AU  - Veys EM
FAU - Baeten, Dominique
AU  - Baeten D
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Immunologic Factors)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - OP401G7OJC (Etanercept)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antirheumatic Agents/*administration & dosage/adverse effects
MH  - Bone and Bones/immunology/pathology
MH  - Cartilage/immunology/pathology
MH  - Down-Regulation/drug effects/immunology
MH  - Etanercept
MH  - Extracellular Matrix/immunology/pathology
MH  - Female
MH  - Humans
MH  - Immunoglobulin G/*administration & dosage/adverse effects
MH  - Immunologic Factors/administration & dosage/adverse effects
MH  - Knee Joint/immunology/pathology
MH  - Male
MH  - Middle Aged
MH  - Receptors, Tumor Necrosis Factor/*administration & dosage
MH  - Spondylarthropathies/*drug therapy/immunology/pathology
MH  - Synovial Membrane/immunology/pathology
MH  - Synovitis/*drug therapy/immunology/pathology
MH  - Treatment Outcome
EDAT- 2005/12/06 09:00
MHDA- 2006/01/13 09:00
CRDT- 2005/12/06 09:00
PHST- 2005/12/06 09:00 [pubmed]
PHST- 2006/01/13 09:00 [medline]
PHST- 2005/12/06 09:00 [entrez]
AID - 10.1002/art.21426 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2005 Dec;52(12):3898-909. doi: 10.1002/art.21426.