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Logo of annrheumdAnnals of the Rheumatic DiseasesCurrent TOCInstructions for authors
Ann Rheum Dis. Sep 2002; 61(9): 804–809.
PMCID: PMC1754213

Soluble adhesion molecules (ICAM-1, VCAM-1, and E-selectin) and vascular endothelial growth factor (VEGF) in patients with distinct variants of rheumatoid synovitis


Background: Cell adhesion molecules and endothelial growth factors have an important role in the infiltrating of rheumatoid synovium with mononuclear cells, leading to the initiation and progression of the disease.

Objective: To investigate whether the serum profile of soluble adhesion molecules and of vascular endothelial growth factor (VEGF) is associated with the histological appearance of rheumatoid arthritis (RA).

Methods: Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), and VEGF were assessed by enzyme linked immunosorbent assay (ELISA) in 40 patients with RA and 32 patients with osteoarthritis (OA).

Results: Histological analysis of synovium specimens distinguished two types of rheumatoid synovitis. Twenty four RA samples presented diffuse infiltrates of mononuclear cells without any further microanatomical organisation, whereas in the remaining 16 samples lymphocytic follicles with germinal centre-like structures were identified. In comparison with patients with OA, constituting a control group, higher serum concentrations of sICAM-1 (p<0.001), sVCAM-1 (p<0.001), sE-selectin (p<0.01), and VEGF (p<0.001) were detected in patients with RA. Raised concentrations of sICAM-1, sVCAM-1, and VEGF dominated in the serum of patients with RA with follicular synovitis compared with those with diffuse synovitis (p<0.01 for all comparisons). The serum concentrations of sICAM-1, sVCAM-1, and VEGF correlated with markers of disease activity such as the erythrocyte sedimentation rate and C reactive protein levels. Furthermore, the clinical data analysed in our study indicated that patients with RA with follicular synovitis tend to have more severe disease.

Conclusions: The distinct histological appearances of rheumatoid synovitis associated with different serum profiles of sICAM-1, sVCAM-1, and VEGF reflect varied clinical activity of the disease and confirm RA heterogeneity. Patients with different histological forms of synovitis may respond differently to the treatment regimens.

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Selected References

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Figures and Tables

Figure 1
Histological pictures of RA and OA synovia. Representative samples are presented for the groups of patients analysed. (A) RA synovium specimen displaying diffuse mononuclear cell infiltrates without specific microanatomical organisation. (B) RA sample ...
Figure 2
Serum concentrations of sICAM-1 in the patients studied. Assessment was based on an ELISA technique. The box plots represent median (line), 25th and 75th centiles (box), and 10th and 90th centiles (whiskers).
Figure 3
Serum concentrations of sVCAM-1. The measurement of sVCAM-1 was performed and shown as described in the legend to fig 2.
Figure 4
Serum concentrations of sE-selectin were analysed and presented as described in the legend to fig 2.
Figure 5
Serum concentrations of VEGF analysed and presented as described in the legend to fig 2.

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