Background:Early definitive diagnosis and effective treatment are mandatory in rheumatoid arthritis (RA) as it can halt the disease progression and subsequent joints destruction.Objective:To investigate the diagnostic and prognostic value of anti-mutated citrullinated vimentin (anti-MCV) and its correlation with disease activity, peripheral and axial skeleton affection in RA patients.Patients and methods:A total of 123 patients with different rheumatic diseases were enrolled in a prospective-two year study at Ain Shams University hospital: 64 patients with RA and 59 patients with other rheumatic diseases as controls. RA patients were fulfilling the traditional and the new ACR/EULAR diagnostic criteria for RA. They have been followed up for two years. At baseline, all RA patients were subjected to: Clinical assessment of disease activity by taking full histories, general and local examination, measurement of 28 joint count of tender and swollen joints with calculation of disease activity score (DAS-28) for each patient. Complete blood count, erythrocytes sedimentation rate, C-reactive protein and rheumatoid factor titers were performed. Anti-MCV IgG immunoglobulins’ assay was performed at the study endpoint by ELISA. RA patients were then classified into; anti-MCV positive and anti-MCV negative groups for statistical comparison. Plain X-ray was performed on the peripheral joints and scored by the Simple Erosion Narrowing score (SEN-score). Magnetic Resonance Imaging (MRI) scans were carried out to 22 RA patients on cervical and lumbosacral regions.Results:Anti-MCV antibodies were found to be of high sensitivity (79.6%) and specificity (96.6%) in diagnosing RA. The area under the curve was 0.893 at 95% confidence interval (CI), confers an odds ratio of 23.5. Anti-MCV positive RA patients had significantly higher DAS-28 and SEN-scores than anti-MCV negative patients; who were found to have more benign disease with lower incidence of erosions (P < 0.05). MRI scans revealed that; 17/22 (77%) had cervical joints involvement while, 8 (36%) had lumbo-sacral joint lesions (P < 0.05), both were correlated significantly with aggressive peripheral joint disease.Conclusion:Anti-MCV antibodies are promising diagnostic and prognostic marker in RA, with high sensitivity and specificity. They may identify a subset of RA patients with aggressive early erosive disease. The axial skeleton—especially the cervical spine—could be affected in RA and this was correlated with aggressive peripheral joints’ disease. MRI scanning is a sensitive method for detecting axial skeleton involvement in RA, in attempt for better disease control and outcomes.
Background
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by erosive synovitis. Early changes in the synovium are marked by neovascularization, synoviocyte hyperplasia, and inflammatory cell infiltration, which produce a pannus of inflammatory vascular tissue (Brenchly, 2001). Nuclear Factor-κB (NF-κB) is a family of transcription factors central to immunity and inflammation. NF-κB plays a pivotal role in the regulation production by inducing transactivation of genes including TNFα, 1L-1, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and intercellular adhesion molecule-1 (ICAM- 1). Basic fibroblastic growth factor (bFGF- FGF2) is a 146 amino acid protein with molecular weight of 18000 and believed to be an autocrine and/or paracrine growth and angiogenic factor.
Objectives
find out and demonstrate the role of nuclear factor-κB (NF-κB) and basic fibroblast growth factor (bFGF) in synovial hyperplasia in rheumatoid arthritis (RA) patients and correlate them with disease activity and severity, if present, in order to throw light on possible new therapeutic strategies in the management of RA.
Methods
25 RA patients, diagnosed according to the American college of Rheumatology (ACR), as well as 10 patients with post-traumatic knee injury served as control group were recruited in this study. Patients and controls were scheduled for either knee joint replacement, arthroscopic knee joint surgery or diagnostic arthroscopy. Disease activity of RA patients was assessed using the modified disease activity score. Disease severity was assessed using the spread severity index (SS index) and larsen method. Synovial biopsies obtained from patients and controls were prepared for routine haematoxylin and eosin staining and immunohistochemical staining of NF-κB and bFGF.
Results
NF-κB was highly significantly increased in RA synovial lining cells and endothelial cells as compared with synovial cells of post- traumatic controls (P>0.001). A highly signficant positive correlation was found between immunostaining of NF-κB in lining, sublining and endothelial cells and each of disease activity assessed by modified DAS,SS index and mean number of synovial cells (P>0.001).A highly significant increased in bFGF expression in the cytoplasm of synoviocytes, fibroblasts, infiltrating cells and endothelial cells in RA synovium compared to synovial cells of post- traumatic controls (p>0.001).
A positive correlation was found between immunostaining of bFGF of RA synovial cells and each of modified DAS, SS index, mean number of synovial cells and mean percentage of vessels with perivascular lymphocytic infiltrates(p>0.05 and p>0.001).
Conclusions
NF-κB and bFGF play a crucial role in the pathogenesis of rheumatoid synovium by inducing synovial hyperplasia and angiogenesis. Inhibition of NF-κB and bFGF may represent a new tool for future therapeutic strategies.
NF-κB and bFGF play a crucial role in the pathogenesis of rheumatoid synovium by inducing synovial hyperplasia and angiogenesi...
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