AB0147 The Effect of B Cells Activated by CYPA-CD147 on the Pathogenesis of Rheumatoid Arthritis
Authors: Z. Wu, X. Li, P. Zhu
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Rheumatoid arthritis (RA) is one of the most common rheumatic diseases, and Its main pathological manifestation is a highly vascularized tissue caused by infiltration of T, B cells and macrophages. CyPA could regulate the expression level of CD147 on cell membrane. which to promote leukocytes of inflammatory response to infiltrate the lesion tissues and played an important role in RA. It suggests that CyPA may induce the chemical chemotaxis by CD147 of neutrophils and monocytes, and induce the chemotaxis of inflammatory cells into synovial fluid of joint cavity, which leads to articular cartilage and bone destruction of RA patients and eventually promotes the development of the disease. However, the underlying inflammatory response of acquired immune response and the interaction between cyclophilin A and CD147 at the B-cell activation stage when specific antibodies are produced still remains unclear. <h3>Objectives</h3> To study the effect of CypA on CD147 expression on B cells in synovium and synovial fluid, and its effect on autoantibodies secreted by B cells. <h3>Methods</h3> Immunohistochemical staining (B cell, follicular dendritic cell, and plasma cell were labeled by CD19, CD35, and CD38) was used to observe the formation of germinal center of B cell in RA synovial tissues. Mononuclear cells in RA synovial fluid were separated and treated with CypA, BAFF and LPS to detect the changes of CD147 expression (the percentage of positive cells and mean fluorescence intensity were recorded) on CD19+ B cells surface by flow cytometry. Supernatant was collected to detect RF subtypes and the level of anti-CCP antibody. <h3>Results</h3> There were special structures like germinal centers in synovial specimens in 13 out of 35 RA patients. The expression of CD147 at different degrees was noted. In CD147-positive cells in RA synovial lymphatic follicle, 30±8% was lymphocyte, 32±7% was follicular dendritic cells, and 38±11% was endothelial cells. Weak expression or no expression of plasma cell was also recorded. The highest CD147 MFI of CD19+ B appeared 48 h after CypA, BAFF and LPS treatment. After treatment, RF and anti-CCP of supernatant were significantly higher than those before treatment (p&lt;0.01). There was no significant difference among CypA, BAFF and LPS (p&gt;0.05). <h3>Conclusions</h3> The interaction between CypA and CD147 involves in the pathogenesis of B cell activation and inflammatory response in RA. Further study will provide new clues for targeted anti-inflammatory therapies. <h3>References</h3> Shlomchik MJ. Sites and stages of autoreactive B cell activation and regulation. Immunity. 2008;28:18-28. Mauri C, Ehrenstein MR. Cells of the synovium in rheumatoid arthritis: B cells. Arthritis Res Ther. 2007;9:205. Zuckerman NS, Hazanov H, Barak M, et al. Somatic hypermutation and antigen-driven selection of B cells are altered in autoimmune diseases. J Autoimmun. 2010;35:325-35. Ohata J, Zvaifler NJ, Nishio M, Boyle DL, Kalled SL, Carson DA. Fibroblast-like synoviocytes of mesenchymal origin express functional B cell-activating factor of the TNF family in response to proinflammatory cytokines. J Immunol. 2005;174:864-70. Cheema GS, Roschke V, Hilbert DM, et a1. Elevated selalm B lymphocyte stimulator levels in patients with systemic immunebased rheumatic diseases. Arthritis Rheum. 2001;44:1313-9. <h3>Disclosure of Interest</h3> None declared