Value of anti-cyclic citrullinated peptide antibodies and magnetic resonance imaging in early rheumatoid arthritis

To assess the value of the presence of anti-cyclic citrullinated peptide antibody [anti-CCPAb] as well as magnetic resonance imaging [MRI] in early rheumatoid arthritis [RA]. The study was performed on twenty early RA patients [with disease duration <1 year] diagnosed according to the 1987 ACR classification criteria. They underwent full history taking and thorough clinical examination. Anti-CCPAb was assessed with ELISA technique. MRI study was done for both wrist joints and hands of all patients and evaluated according to the OMERACT 2002 RAMRIS scoring system. Disease activity was assessed with CRP and 28 joint disease activity score [DAS28]. Rheumatoid factor [RF] IgM was analyzed with latex agglutination. We divided the patients according to the presence or absence of anti-CCP antibodies into two groups: Eleven [55%] patients were positive for anti-CCP and 9 [45%] patients were anti-CCP negative. Comparison between the two groups revealed that there was a highly statistical significant difference as regards the CRP level and DAS28 score [p<0.001]. There was a statistically significant difference in the initial presentation between the two groups; in anti-CCP positive patients symptoms started more often in the upper limbs while the anti-CCP negative group they often presented in both upper and lower limbs. Bone marrow edema was more frequent in patients with positive than those with negative anti-CCP-Ab with a highly statistical significant difference [p<0.001]. The highest global scores for bone edema were seen in triquetral and lunate bones. The prevalence and severity of synovitis as well as the MRI scoring of bone erosions did not differ significantly between the two groups [p>0.05]. The highest global score of erosions was located in the same sites in the wrist and MCP joints. Tenosynovitis was observed nearly equally in both groups of patients. Global scores of tenosynovitis in both groups were high in the extensor tendons of the wrist and in the flexor tendons of the MCP joints. The study showed the importance of the presence of positive anti-CCPAb at baseline and its high association with greater disease activity [DAS28], higher levels of CRP, and bone marrow edema as an indicator of future bone erosion in early RA. MRI can be added as a useful tool for evaluation of early RA. This aspect is important because an early diagnosis of RA may modify the therapeutic strategy substantially, suggesting the use of more aggressive pharmacological agents that can delay progression of joint damage and thus substantially change the natural history of the disease

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

Role of placental growth factor and high resolution ultrasound in evaluation of hypervascularity in psoriatic arthritis

To measure the levels of placental growth factor [PIGF] in the serum and synovial fluid of in psoriatic arthritis [PsA] patients. Also, to evaluate any possible role of high resolution US in the angiogenesis observed in this disease. The study was conducted on 25 PsA patients and 10 apparently healthy age and sex matched subjects who served as controls. All subjects were subjected to thorough clinical and laboratory examination. PIGF levels were measured in the serum of all of them with ELISA technique. This was confirmed with Western blotting for PIGF in synovial fluid. Assessment of vascularity of the small joints of the hands and other affected knee joints with high resolution US was performed. The mean value of serum PIGF level in the serum of PsA patients was [66.52 +/- 12.44 pg/ml] and that in the synovial fluid was 79.82 +/- 14.92]. There was a highly statistical significant difference between them and serum/synovial fluid levels in controls [16.20 +/- 7.33 and 19.44 +/- 8.79 pg/ml] respectively [p<0.001]. Moreover, there was a highly significant association [p<0.001] and a statistically significant positive correlation [p<0.05] between serum and synovial fluid levels of PIGF in PsA patients. There was a statistically significant difference between PsA patients and controls as regard Hb levels, ESR and serum uric acid [p<0.05]. Also, there was a significant positive correlation between synovial fluid PIGF levels and the onset of joint affection [p<0.05]. High resolution US can measure the synovial thickness in the small joints of the hands as well as knee joints in PsA patient. It can also detect increased blood flow in joints, so can measure the resistive index and can detect effusion. Our results showed that there was a highly statistical significant difference between PsA patients and controls as regard synovial thickness [p<0.001]. Also, there was a significant negative correlation between serum PIGF and resistive index of PsA patients Angiogenesis plays an important role in the pathogenesis of PsA. This is confirmed by the presence of higher PIGF levels in both serum and synovial fluid. Inhibition of PIGF and its receptor [Flt-1] constitute potential candidates for therapeutic modulation of angiogenesis and inflammatory joint destruction in arthritis. High resolution ultrasound can be very useful to detect early hypervascularization and joint inflammation which guide treatment towards an early or more aggressive therapy

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

Clinical significance of serum thrombomodulin level in rheumatoid arthritis patients

To determine the soluble thrombomodulin [TM] level in sera of rheumatoid arthritis [RA] patients and to evaluate its relationship to disease activity in those patients. Twenty rheumatoid arthritis patients were included in this study. They were 18 females and 2 males. Their age ranged from 25 to 62 years. The Disease Activity Score [DAS] was used for the assessment of disease activity in the patients. The DAS was divided into 3 categories: 2.4 and 3.7 [high disease activity]. Ten age and sex-matched healthy subjects were included as a control group. The soluble thrombomodulin level was measured with a solid phase sandwish-Enzyme-Linked-Immuno-Sorbent Assay [ELISA] in the sera of the twenty RA patients and ten controls. The relationship between serum TM levels and disease activity in the patients was assessed. The frequency of patients with high serum TM levels [> 5.33 ng/ml] was 7/20 [35%]. Serum TM levels in the patients were significantly higher than those in the control group [p < 0.05] and there was a significant positive correlation between serum TM levels and the DAS [p < 0.05]. Comparison between patients with different categories of the DAS and controls regarding serum TM level showed that patients with high disease activity [DAS > 3.7] had a highly significant higher serum TM levels than the control group [p < 0.001]. Patients with moderate disease activity [DAS > 2.4 and 0.05]. Serum TM levels were elevated in RA patients and correlated with the disease activity score. These results may indicate that serum TM measurement may be valuable in the evaluation of the RA disease activity