Serum and synovial fluid levels of vascular endothelial growth factor in rheumatoid arthritis: correlation with disease activity

To study serum and synovial fluid levels of vascular endothelial growth factor [VEGF] in Rheumatoid arthritis [RA] and to investigate its association with clinical and laboratory parameters in order to assess its value as a marker of disease activity and development of joint synovitis. Measurement of VEGF levels in serum of 40 RA patients, synovial fluid obtained from 15 patients of them and 10 healthy age and sex matched subjects taken as controls using enzyme linked immunosorbent assay [ELISA] technique. Subjects underwent thorough clinical examination, assessment of disease activity using disease activity score [DAS] and radiological evaluation using the Larsen scale. Serum VEGF levels in RA patients [436.5 +/- 286.3 pg/ml] and that in synovial fluid [640.7 +/- 305.4 pg/ml] were significantly higher than in controls [252.0 +/- 51.6 and 276.0 +/- 48.8 pg/ml] respectively [p<0.001]. Twenty two RA patients out of 40 [55%] had increased serum VEGF while 14 RA patients out of 15 [93.3%] had increased synovial fluid VEGF There was a highly significant difference between serum VEGF [590.9 +/- 303.2 pg/ml] and synovial fluid VEGF [756.0 +/- 313.8 pg/ml] of RA patients [p<0.001]. Moreover, there was a statistically significant positive correlation between serum and synovial fluid VEGF [p<0.05] of RA patients. Also, there was a highly significant difference [p<0.001] and a significant positive correlation [<0.05] between serum VEGF and 28 swollen joint count, ESR, DAS score and Larsen grades. Again, there was a statistically significant difference [p<0.05] and significant positive correlation [p<0.05] between serum VEGF and age and 28 tender joint count while there was a significant negative correlation with Hb level [p<0.05]. Serum and synovial fluid VEGF levels were increased in RA patients and reflect the extent of joint disease severity. So VEGF levels can be a reliable marker in assessment of early active joint destruction in RA patients and evaluate the antiangiogenic therapy especially with VEGF inhibitors, which can represent a novel therapy for RA in the future

Serum matrix metalloproteinases [MMP-3, MMP-9] and tissue inhibitor of metalloproteinase-1 [TIMP-1] in rheumatoid arthritis, psoriatic arthritic and osteoarthritis

To investigate whether serum levels of MMPs and TIMPs are specifically elevated in rheumatoid arthritis as compared to other inflammatory and degenerative joint diseases. We compared serum levels of matrix metalloproteinases [MMP-3, MMP-9] and tissue inhibitor of metalloproteinase [TIMP-1] of RA with psoriatic arthritis [PsA] and osteoarthritis [OA]. Serum samples were obtained from 30 RA, 20 psoriatic arthritis and 30 knee osteoarthritis patients. Serum concentration of stromelysin-1 [MMP-3], gelatinase B [MMP-9] and TIMP-1 were measured with quantitative sandwich enzyme-linked immunosorbent assay [ELISA] technique. Clinical examination and assessment of disease activity in RA using disease activity score [DAS] were carried out. Radiological evaluation in RA patients using the Larsen scale and in OA patients using the Kellgren and Lawrence scale were also done. Unique serum profiles of MMPs and TIMP-1 were identified in the two inflammatory arthritis groups [RA and PsA]. The serum concentrations of MMP-3 and MMP-9 were significantly higher in RA patients than in OA patients used as a control groups [p<0.001]. These two MMPs dominated in the serum of RA patients than PsA patients [p<0.001]. The analysis of the serum concentrations of TIMP-1 was also elevated in RA patients as compared with OA knee patients [p<0.001]. Also TIMP-1 was found in a significantly higher concentration in the serum of RA patients than PsA patients [p<0.05]. MMP-3 and MMP-9 correlate significantly with disease activity [DAS] in RA patients and with radiological scores. Serum levels of MMP-3, MMP-9, and TIMP-1 were significantly higher in RA and PsA than OA patients. MMP-3 and MMP-9 could be specific markers of joint inflammation and destruction. These variables are neither specific for RA nor for diseases in which bone erosions occur. These markers were correlated with the clinical activity of the disease. Early detection of these markers may herald progressive course and modulate the lines of treatment