Analysis of the cell infiltrate and expression of proinflammatory cytokines and matrix metalloproteinases in arthroscopic synovial biopsies: comparison with synovial samples from patients with end stage, destructive rheumatoid arthritis.
BACKGROUND
Synovial tissue (ST) from end stage destructive rheumatoid arthritis (RA) and arthroscopic biopsies obtained during active inflammation might exhibit different characteristics.


OBJECTIVE
To define the cell infiltrate and the expression of proinflammatory cytokines, angiogenic factors, and matrix metalloproteinases (MMPs) in ST selected at arthroscopy compared with that from end stage RA.


METHODS
Synovial biopsy specimens were obtained from the actively inflamed knee joints of 13 patients with chronic RA by arthroscopy and compared with ST from 10 patients with end stage, destructive RA. Immunohistological analysis was performed to detect T cells, plasma cells, macrophages, fibroblast-like synoviocytes (FLS), and the expression of interleukin (IL)1beta, IL6, tumour necrosis factor alpha (TNFalpha), MMP-1, MMP-3, MMP-13, TIMP-1, and VEGF.


RESULTS
The expression of CD68+ macrophages was significantly higher in ST selected at arthroscopy than in samples obtained at surgery, both in the intimal lining layer and in the synovial sublining. The expression of CD3+ T cells also tended to be higher in arthroscopic samples. The expression of TNFalpha, IL6, MMP-1, MMP-3, MMP-13, TIMP-1, and VEGF was on average higher in ST obtained at arthroscopy. In contrast, the expression of IL1beta was on average higher in surgical samples.


CONCLUSIONS
Active arthritis activity is associated with increased cell infiltration, expression of proinflammatory cytokines, MMPs, and angiogenic growth factors in synovial biopsy samples selected at arthroscopy. Increased expression of IL1beta in the synovium of patients with destructive RA requiring joint replacement may well reflect the important role of IL1beta in cartilage and bone destruction.
Smeets
T J M
TJ
Division of Clinical Immunology and Rheumatology, Academic Medical Centre/University of Amsterdam, Amsterdam, The Netherlands. T.J.Smeets@amc.uva.nl
Barg
E C
EC
Kraan
M C
MC
Smith
M D
MD
Breedveld
F C
FC
Tak
P P
PP
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology* / Q000601:surgery; D019645:Arthroplasty, Replacement, Knee; D001182:Arthroscopy; D001706:Biopsy; D017252:CD3 Complex / Q000276:immunology; D017364:Collagenases / Q000032:analysis; D016207:Cytokines / Q000032:analysis*; D016228:Endothelial Growth Factors / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis; D007375:Interleukin-1 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D007719:Knee Joint; D007962:Leukocytes / Q000276:immunology*; D008222:Lymphokines / Q000032:analysis; D008264:Macrophages / Q000276:immunology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000032:analysis; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3 / Q000032:analysis; D020782:Matrix Metalloproteinases / Q000032:analysis*; D008875:Middle Aged; D010950:Plasma Cells / Q000276:immunology; D018709:Statistics, Nonparametric; D013583:Synovial Membrane / Q000276:immunology* / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017252:CD3 Complex; D017364:Collagenases; D016207:Cytokines; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D008222:Lymphokines; D020781:Matrix Metalloproteinase 1; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3; D020782:Matrix Metalloproteinases; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C507079:MMP13 protein, human