Clinical manifestation of systemic vasculitis may be postulated as a consequence of the immune response abnormalities in the course of connective tissue diseases (CTD). The aim of this study was to elucidate the significance of the different autoantibodies and soluble intercellular adhesion molecule 1 (sICAM-1) shedding into the circulation in the diagnosis of vasculitis in rheumatic diseases. Serum of 86 patients with rheumatic diseases (54 with rheumatoid arthritis (RA) and 32 with CTD) were analyzed for the concentrations of sICAM-1 levels by the enzyme linked immunosorbent assay (ELISA). Control sera were obtained from 30 healthy individuals. Anti-nuclear antibodies (ANA), anti-double-stranded antibodies (anti-dsDNA) and anti-proteinase-3 (PR-3) antibodies (anti-neutrophil cytoplasmic autoantibodies cytoplasmic specific, cANCA) were assessed by the ELISA method. Fifty out of 86 patients had the systemic lesions. Pathological picture of the vascular loop in the nailfold capillary microscopy was found in 84 patients. In 19 patients the microvascular changes were advanced, in 35 moderate and in 30 mild. All patients with the articular manifestations had the pathological changes in the capillary microscopy. Patients with advanced changes in the capillary microscopy had the longer disease duration compared to patients with mild intensity of vasculitis. Serum concentration of sICAM-1 was significantly increased in RA and CTD patients compared to 30 controls (in both cases p<0.001). Moreover, RA and CTD patients with the systemic vasculitis showed significantly higher levels of sICAM-1 than those without vascular involvement (respectively p<0.001 and p<0.005). ANA were observed in significantly elevated concentration among RA and CTD patients with the systemic damage compare to patients without organ injury (respectively p<0.001 and p<0.05). Also cANCA level was twice more higher but only among CTD patients with the systemic damage (p<0.05). Serum concentration of sICAM-1 was elevated in studied patients with the presence of ANA antibodies (p<0.05). Significant correlation between ANA level and the disease duration, and hemoglobin concentration were observed. The concentration of cANCA correlated with rheumatoid factor and of dsDNA with patient age. We conclude that the systemic lesions in the course of RA and CTD are accompanied by the microvascular injury in nailfold capillary microscopy. Our data suggest that sICAM-1, ANA and cANCA serum levels may reflect the extent of the vascular involvement in RA and CTD patients.
The diagnostic category of rheumatoid arthritis, a syndrome of chronic inflammatory disease of the synovial membrane and of extraarticular tissues, covers a broad spectrum of clinical phenotypes. Here we propose that distinct combinations of disease risk genes produce heterogeneity of rheumatoid disease. Recognition of this genetic and clinical heterogeneity has immediate implications as it provides the opportunity to develop selective therapies for the different variants of disease.
Introduction: The aim of the study was to evaluate whether vascular endothelial growth factor (VEGF) serum level is associated with systemic organ involvement, microvascular changes as determined by nailfold capillaroscopy, and disease activity of systemic lupus erythematosus (SLE). Materials and Methods: Serum levels of VEGF were determined by an enzyme-linked immunosorbent assay in 47 SLE patients and in 30 healthy controls. Nailfold capillaroscopy was performed in all patients and healthy subjects. Results: Morphological changes were observed by nailfold capillaroscopy in 45 of 47 (95.7%) SLE patients. Mild capillary changes were found in 16 (34%), moderate in 21 (44.7%), and severe in 8 (17%) SLE patients. All patients with systemic organ involvement showed severe or moderate changes in nailfold capillaroscopy. In comparison with the control group, a higher serum concentration of VEGF in SLE patients was demonstrated (p<0.05). Furthermore, significant differences in VEGF serum concentration between SLE patients with systemic involvement and controls were found (p<0.01). Comparison between patients with active and inactive SLE according to SLEDAI score showed a significantly higher concentration of VEGF in the sera of patients with active SLE (p<0.01). The SLE patients with severe and moderate changes in nailfold capillaroscopy showed significantly higher VEGF serum levels than SLE patients with mild changes (p<0.05) or healthy controls (p<0.01). Moreover, the VEGF serum level correlated significantly with ESR (r=0.580, p<0.0001) and CRP (r=0.512, p<0.005). Conclusions: Our data suggest that VEGF serum level may be a useful marker of disease activity and internal organ involvement in SLE patients. Abnormalities in nailfold capillaroscopy may reflect the extent of microvascular involvement and are associated with systemic manifestation in SLE. Abbreviations: SLE ? systemic lupus erythematosus, VEGF ? vascular endothelial growth factor, SSc ? systemic sclerosis, RA ? rheumatoid arthritis, CTD ? connective tissue disease, SLEDAI ? Systemic Lupus Erythematosus Disease Activity Index, HRCT ? high-resolution computed tomography, ESR ? erythrocyte sedimentation rate, CRP ? C-reactive protein.
The purpose of this study was to determine the effect of repeated infusions of infliximab, a chimeric anti-tumor necrosis factor (anti-TNF)- alfa antibody, on the levels of soluble adhesion molecules and vascular endothelial growth factor (VEGF) in patients with active rheumatoid arthritis (RA). The treatment design consisted of 9 infusions of infliximab (3 mg/kg)at weeks 0,2,6,and every 8 weeks thereafter. All patients had been receiving methotrexate (MTX;7.5 ?20 mg/week).Serum levels of soluble intercellular adhesion molecule (sICAM)-1,vascular cell adhesion molecule (sVCAM)-1,E-selectin (sE-selectin), and VEGF were measured by ELISA at weeks 0,2,6,14,and 38 prior to infusion, and at week 62. A remarkable decrease in serum sICAM-1 (p<0.001),sVCAM-1 (p<0.01), sE-selectin (p<0.01)and VEGF (p<0.001)levels was observed in RA patients after the initial dose of infliximab. The second administration of the drug was followed by an even more significant suppression of serum sICAM-1,sVCAM-1,sE-selectin,and VEGF (p<0.001 in all cases). Further infliximab infusions also significantly reduced serum soluble adhesion molecules and VEGF concentrations, although these were less effective. Infliximab treatment induced a significant decrease in the number of monocytes observed until the end of the study. Our study, besides a rapid suppression of disease activity, showed that serum soluble adhesion molecules and VEGF concentrations are down-regulated following anti-TNF-? antibody therapy combined with MTX. Repeated doses of infliximab sustained the reductions in the soluble adhesion molecules and VEGF concentrations, although they were less effective than the first and second infusions of infliximab.
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