SAT0019 HISTOPATHOLOGICAL CHANGES OF SYNOVIAL TISSUE IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH TNF INHIBITORS
Authors: Y. Takashima, K. Fukuda, S. Hayashi, T. Kamenaga, M. Fujita, K. Kikuchi, R. Kuroda, K. Funahashi, T. Matsubara
Journal: Annals of the Rheumatic Diseases (2020)

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by hyperplasia of synovial tissues [1]. Tumor necrosis factor (TNF)-α is one of the pro-inflammatory cytokines that play a crucial role in the pathogenesis of RA synovitis, and TNF inhibitors (TNFi) were reported to force the RA to go into remission or low disease activity and have brought revolutionary impacts on RA treatment [2]. TNFi have been shown to act on inflammatory cells and form the discoid fibrosis in the sublining layers [3,4]. However, the changes of synovial tissue and the cause of discoid fibrosis in RA patients treated with TNFi has not been determined in detail. Objectives: The purpose of this study is to demonstrate the histological changes and the types of cells around discoid fibrosis in RA synovium treated with TNFi . Methods: Synovial tissues were obtained from 30 patients with RA during joint surgeries. 6 patients were treated with TNFi (1 patient with golimumab, 3 patients with etanercept, 2 patients with infliximab). As a control, synovial tissues were obtained from 6 patients who were treated only with csDMARDs (6 patients with MTX). The frozen sections were stained by hematoxylin and eosin (HE). To detect the apoptosis, TdT-mediated dUTP nick end labeling (TUNEL) was performed. The immunohistochemical characterization of the synovial cells was performed by using following antibodies: CD20 and CD3 for detecting B and T lymphocytes respectively, CD163 and CD86 for detecting M1 and M2 macrophage respectively. Results: In the sections stained with HE, the formation of discoid fibrosis and the other characteristic changes including hydropic degeneration, vacuolation, sclerosis of small vasculature, and the number of multilayered synovial cells was decreased in synovium from RA patients treated with TNFi. In the sections with TUNEL stain, apoptosis of lining cells around the discoid fibrosis was detected in RA synovium treated with TNFi (Figure 1a, 1b). In the sections with immunohistochemistry stain, CD86 expression increased in lining layer of RA synovium treated with TNFi. CD163 positive cells showed diffuse expression in RA synovium treated with TNFi. In contrast, CD20 and CD3 positive cells decreased around discoid fibrosis compared to control sections. These results showed indicated that the types of cells in lining and sublining layers were mainly macrophages and that the apoptosis of macrophages might form the discoid fibrosis in lining layers. Conclusion: This study showed the apoptosis of lining cells derived from macrophages resulted in the formation of the discoid fibrosis. These findings indicated TNFi might induce apoptosis of macrophage leading to the suppression of RA synovitis. References: [1] Scott Dl, et al. Progression of radiological changes in rheumatoid arthritis. Ann Rheum Dis. 1984. [2]van der Heijde D,et al. Comparison of etanercept and methotrexate, alone and combined, in the treatment of rheumatoid arthritis: two-year clinical and radiographic results from the TEMPO study, a double-blind, randomized trial. Arthritis Rheum. 2006. [3] Hirohata S,et al. TNF inhibitors induce discoid fibrosis in the sublining layers of the synovium with degeneration of synoviocytes in rheumatoid arthritis. Rheumatol Int. 2013. [4] Yamanaka H,et al. Scoring evaluation for histopathological features of synovium in patients with rheumatoid arthritis during anti-tumor necrosis factor therapy. Rheumatol Int. 2010. Acknowledgments : This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Disclosure of Interests: None declared