AB1301 Role of nuclear factor-κB and basic fibroblast growth factor in synovial pathology of rheumatoid synovitis
Authors: S.E. Ibrahim, N. Kamel, M. Zamzam, H. Elshamy, M. Salman
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> 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. <h3>Objectives</h3> 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. <h3>Methods</h3> 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. <h3>Results</h3> NF-κB was highly significantly increased in RA synovial lining cells and endothelial cells as compared with synovial cells of post- traumatic controls (P&gt;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&gt;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&gt;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&gt;0.05 and p&gt;0.001). <h3>Conclusions</h3> 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 angiogenesis. Inhibition of NF-κB and bFGF may represent a new tool for future therapeutic strategies. <h3>Disclosure of Interest</h3> None Declared