Possible role of serum levels of vascular endothelial growth factor and endostatin in rheumatoid arthritis angiogenesis imbalance

To measure serum levels of the main angiogenic inducer marker [VEGF] and the main angiogenic inhibitor marker [endostatin] in rheumatoid arthritis patients. Also, to study their correlation to clinical and laboratory variables of the disease in an attempt to provide more insight regarding their possible role in the angiogenesis imbalance and pathogenesis of RA. Twenty RA patients and fifteen age and sex matched healthy persons served as a control group underwent full history taking, thorough clinical examination, and routine rheumatological profile. Measurement of serum VEGF and endostatin levels were done using enzyme linked immunosorbent assay [ELISA] in rheumatoid arthritis patients and compared with controls. Comparison between patients with or without systemic involvement regarding serum level of VEGF was done. Correlations between serum levels of VEGF and signs of disease activity were also done. A highly significant increase in the mean values of serum VEGF was found in RA patients compared to control subjects [t=11.83, p<0.00l], while there was no statistically significant difference between both RA and control groups regarding mean values of endostatin [t=0.06, p>0.05]. In addition a highly significant increase in the mean values of serum VEGF was found in RA Patients with extra-articular manifestation [EAM] compared to Patients without EAM [t=2.98, p<0.0l]. Serum VEGF was positively correlated with ESR, DAS, and CRP [r =8.48, p<0.01; r = 0.542, p< 0.5; and r = 0.49, p< 0.5] respectively. We found an imbalance between the production of angiogenic growth factors and angiogenic inhibitors in RA. This may play an important role in the angiogenesis imbalance and pathogenesis of RA. In addition we conclude that VEGF level is related to disease activity and extra-articular manifestation of RA, so it can be considered a good indicator for evaluation of disease activity, systemic organ involvement and planning treatment strategies

Hyaluronate as a biomarker for rheumatiod arthritis activity

Hyaluronic Acid [HA] in synovial tissue may leak into the circulation during synovial inflammation. So serum HA levels are expected to be elevated in rheumatic diseases with synovial involvement such as rheumatoid arthritis. To study the clinical specificity of HA for rheumatoid arthritis [RA] as a possible biomarker related to cartilage and bone turnover and its relation to disease activity. Serum samples from 50 RA were tested. 20 serum samples from healthy blood donors were used as controls. HA serum level in ng/ml was determined using an ELISA-based assay, and correlated with the clinical and laboratory variables. RA patients had mean age 45.9 +/- 7.8 SD years and duration of disease was 2.4 +/- 1.2 years. The study showed significant correlations between the serum HA level and the indices of disease activity, joint swollen scores [R=0.77, p<0.05], morning stiffness [R=0.67, p<0.05], erythrocyte sedimentation rate [ESR] [R = 0.78, p<0.05], C-reactive protein [CRP] [R=0.79, p<0.05] in RA patients. There was significant correlation with disease duration [R=0.68, p<0.05] and Ritchie articular index [RAI] [R=0.82, p<0.05]. No significant correlation of HA level with age of RA patients was observed [R=-0.28, p>0.05]. Serum HA level is a useful marker for the activity and severity of disease in RA patients

Vascular endothelial growth factor and BCL-2 oncogene in systemic lupus erythematosus

Angiogenesis and defective regulation of programmed cell death [apoptosis] may play a role in the pathogenesis of autoimmune diseases. We aimed to assess the role of the angiogenic cytokine vascular endothelial growth factor [VEGF] and the oncogene Bcl-2 as markers of systemic lupus erythematosus [SLE] disease activity, with particular emphasis on their relation to lupus nephritis [LN]. Using the ELISA technique, VEGF and Bcl-2 plasma levels were measured in 40 SLE patients and 20 healthy matched controls. SLE disease activity index [SLEDAI] was assessed; renal biopsy was taken from 15 patients with manifestations of LN. VEGF plasma level was significantly higher in SLE patients than in controls, and significantly increased in patients with LN. Immuno-staining of LN renal tissue samples showed a strong expression of VEGF. No significant difference was found in Bcl-2 levels between SLE patients and the controls but there were increased levels in active SLE patients as compared to inactive ones. There was a positive correlation between each of VEGF and Bcl-2 and SLEDAI. VEGF and Bcl-2 may serve as markers of SLE activity. VEGF can be used as a reliable non-invasive marker for follow-up of patients with LN

Peripheral blood lymphocytes apoptosis in juvenile idopathic arthritis: relation to disease activity and type of onset

Abnormalities in the mechanisms regulating apoptosis may have a role in the pathogenesis of autoimmune disorders. The aim of this study was to evaluate the incidence of apoptosis of peripheral blood [PB] lymphocytes in children with juvenile idiopathic arthritis [JIA] and correlating it with CD95 [APO-1/Fas] antigen expression and serum levels of sFas and interleukin-15 [IL-15] in different types of onset and activity of the disease. PB lymphocytes apoptotic index [AI], CD95 [APO-1/Fas] antigen expression, serum levels of sFas and IL-15 were detected in 30 cases of JIA and 20 healthy controls. Results were correlated with the type of onset, activity of the disease and acute phase indicators [ESR, CRP]. The mean values of AI, CD95, sFas and IL-15 were higher in children with JIA than in healthy controls. Significant difference was only found for AI especially with systemic type of onset and high activity. Also the levels of IL-15 increased with activity especially in the systemic type. Moreover, AI showed a significant positive correlation with ESR and CRP but not with IL-15, CD95, or sFas. AI of lymphocytes was high in systemic onset JIA and in active disease and correlated with ESR and CRP, but not with IL-15, CD95 expression or serum sFas

Simultaneous combined measurement of antikeratin antibody and rheumatoid factor: additive value in the diagnosis of rheumatoid arthritis

Rheumatoid arthritis [RA] is a systemic inflammatory autoimmune disease of unknown etiology characterized by chronic polyarthritis. Its highly variable and unpredictable course is the underlying reason for the search for new and more sensitive and specific laboratory markers. The only serologic test routinely used in RA assessment is the determination of rheumatoid factor [RF] in the serum. Although RF has sensitivity up to 80%, still it lacks specificity. To evaluate a new marker "antikeratin antibody" [AKA] regarding its sensitivity and specificity and its relation to disease activity. Also the combined RF and AKA, does it add to the diagnosis of RA. Sera from 88 consecutive RA patients, 40 disease controls and 50 healthy controls were tested for RF with latex agglutination and AKA with indirect immunofluorescence assay that used rat esophagus as a substrate. The proportion of RA patients who had AKA [49/88] was higher than in healthy controls 4/50 [X[2]=28.6, p<0.001], and in disease controls 5/40 [X[2] =19.2, p<0.001]. AKA gives weaker sensitivity than RF [55.7%], but stronger specificity [87.5% versus other rheumatic, and 92% versus healthy controls]. The frequency of AKA positivity was higher among patients who had severe disease [being positive in 41/50 of active RA patients], this gives a highly significant association p<0.001. Also, AKA shows significant positive association with RF+ve results [45/71]. Combined results of both AKA and RF gave overall best results as both positive results gave a sensitivity of 97.7%, and both negative results gave a specificity of 97.5% versus rheumatic and 98% versus healthy controls. AKA adds a valuable diagnostic tool in the diagnosis of RA. It is more specific than RF. Its positivity is associated with active RA disease. Combined AKA and RF measurement gives the best sensitivity and specificity for diagnosing rheumatoid disease than each test individually

Serum and synovial fluid levels of MMP-3 and TIMP-1 in rheumatoid arthritis and osteoarthritis

Matrix metalloproteinases [MMPs] are cytokine-modulated enzymes that play an important role in the pathogenesis of RA by inducing bone resorption and cartilage destruction. Tissue inhibitors of metalloproteinases [TIMPs] are naturally occurring MMPs inhibitors. In rheumatoid arthritis [RA], there is a disturbed balance between MMPs and TIMPs favoring proteolysis. This study was performed to evaluate the significance of measuring the serum and synovial fluid [SF] levels of MMP-3 and TIMPs in RA and osteoarthritis [OA] patients in an attempt to provide more insight in their role in the pathogenesis of those two diseases. Serum levels of MMP-3 and TIMP-1 were measured from 30 RA, 20 OA patients and 20 healthy controls using double-antibody ELISA. Also, their levels were measured in the SF of 14 RA and 9 OA patients. RA disease activity was assessed using the Multivariate Analysis of Mallya and Mace and joint erosions were assessed using Larsen score. Serum and SF levels of MMP-3 and TIMP-1 were significantly higher in RA than OA patients and in OA patients than controls. Their levels were significantly higher in the SF than in the serum. Serum and SF TIMP-1: MMP-3 ratio was significantly lower in RA as compared to OA patients and normal controls and this ratio was significantly lower in the SF than in the serum of RA patients. Serum levels of MMP-3 and TIMP-1 correlated strongly with clinical and laboratory parameters of rheumatoid disease activity, and the serum levels of MMP-3 showed a significant positive correlation with the number of joint erosions but TIMP-1 levels did not show this positive correlation. Serum and SF MMP-3 and TIMP-1 levels were significantly higher in RA than OA patients and normal controls. They appear to play a critical role in joint inflammation and destruction, especially MMP-3, which may serve as an additional marker for assessment of RA disease activity and severity