FRI0405 A novel animal model for systemic sclerosis induced by immunisation of angiotensin ii receptor 1. (12th June 2018)

• Record Type: Journal Article
• Authors: Yue, X.; Petersen, F.; Wang, X.; Heidecke, H.; Riemekasten, G.; Yu, X.
• Is Part Of: Annals of the rheumatic diseases. Volume 77(2018)Supplement 2
• Page Start: 735
• Page End: 735
• Publication Date: 2018-06-12
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2018-eular.1898
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Systemic sclerosis (SSc) is a complex connective tissue disease which is characterised by autoimmunity, vasculopathy and fibrosis 1 . Our recent study showed that the progression of SSc was strongly associated with the autoantibodies against angiotensin II receptor I (AT1R), suggesting a role of autoimmunity to AT1R in the pathogenesis of the disease 2 Objectives: In this study, we aimed to investigate the role of AT1R in the pathogenesis of SSc in mice. Methods: C57BL/6J mice were immunised with membrane extract (ME) of CHO cell overexpressing human AT1R or with ME of CHO cells as control. Serum, lung and skin samples were collected and assessed 63 days after immunisation for autoantibody production, inflammation and fibrosis, which are hallmarks for SSc. Results: Immunisation with hAT1R induced the production of autoantibodies against the receptor in mice, and autoantibody deposition was found in the lung. Histologically, mice immunised with hAT1R showed a SSc-like disease, including perivascular infiltrates and fibrosis in the skin as well as pulmonary inflammation. The inflammation in the skin and the lung were characterised by infiltration of T- and B-cells. Furthermore, transfer of immune cells from hAT1R-immunised mice into C57BL/6J mice induced inflammation in the lung. Conclusions: This study demonstrates that immunisation with hAT1R can induce a SSc-like disease, thus showing a pathogenic role of autoimmunity to AT1R and providng a novel mosue model for the diseases. Furthermore, this study also introduces a new immunisation strategy to generate functional autoantibodies against receptors on the cell membrane. References: [1] LeRoy EC, Black C, Fleischmajer R, et al. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol. 1988;15(2):202–205. [2] Riemekasten G, Philippe A, Nather M, et al. Involvement of functional autoantibodies against vascular receptors in systemic sclerosis. Ann Rheum Dis. 2011;70(3):530–536. Disclosure of Interest: None declared