ANTI-MITOFUSIN-1 AND THROMBOSPONDIN-1 AS POTENTIAL MARKERS FOR POLYMYALGIA RHEUMATICA

L. Johansson, D. Michailidou, S. Rantapää Dahlqvist, C. LoodUmeå University, Department of Public Health and Clinical Medicine, Umeå, Sweden University of Washington, Division of Rheumatology, Seattle, United States of America  Background Polymyalgia rheumatica (PMR) is a chronic, inflammatory disorder characterized by aching and stiffness in the proximal regions of the extremities and elevated markers of inflammation. PMR and giant cell arteritis (GCA) are two conditions frequently coexisting [1,2], with increased incidence of large vessel vasculitis and aneurysm development found at long term follow-up. Furthermore, PMR can be one of the manifestations of GCA in 20-40% of cases [3]. The etiology of the diseases are still largely unknown, and specific serological markers, including to monitor arterial disease, are lacking. Recent studies have shown that mitochondrial dysfunction may play a central role in immune activation and could act as a potential source of antigens, including mitofusin-1 (MFN1), in autoimmune diseases [4,5,6]. Objectives To determine whether patients with PMR, with or without overlapping GCA, have elevated levels of markers of platelet activation (e.g. thrombospondin-1; TSP-1), and mitochondrial autoantibodies (e.g. anti-MFN1). Methods Plasma levels of anti-MFN-1 IgG and TSP-1 were measured in healthy controls (HC) (n=30) and patients with PMR (n=60), before and after treatment with glucocorticoids using in-house and commercial ELISAs, respectively. Results Plasma levels of anti-MFN-1 IgG and TSP-1 were elevated in patients with PMR, compared with HC, both before and after treatment with corticosteroids (p<0.001). The highest levels of anti-MFN-1 and TSP-1 were found before treatment of corticosteroids (p<0.001). Co-existence of GCA did not affect levels of either anti-MFN1 or TSP-1, nor treatment response to corticosteroids. Elevated levels of TSP-1 were found to be significantly elevated in patients with symptoms from hips/glutes (n=39) as compared to patients without these symptoms (n=13), median (P25-P75) 27.11 ug/mL (22.5-35.0) vs 19.6 ug/mL (14.1-27.9), p=0.046. Lower concentration of anti-MFN1 IgG was found in patients with symptoms from the spine (n=31) in comparison with those without symptoms from the spine (n=21), median (P25-P75) 0.37 U/mL (0.27-0.57) vs 0.54 U/mL (0.47-0.96), p=0.043. Conclusion Increased levels of anti-MFN-1 IgG and TSP-1 were found in PMR patients and decreased significantly after treatment with corticosteroids, although still significantly higher than HC. The highest concentration of TSP-1 was found in individuals with symptoms from hips/glutes. Increased concentrations of anti-MFN-1 and TSP-1 are suggested as novel biomarkers for PMR and further, could serve as potential biomarkers for treatment response. References Michet CJ, Matteson EL. Polymyalgia rheumatica. BMJ. 2008 Apr 5;336(7647):765-9. Brooks RC, McGee SR. Diagnostic dilemmas in polymyalgia rheumatica. Arch Intern Med. 1997 Jan 27;157(2):162-8. Dejaco C et al. The spectrum of giant cell arteritis and polymyalgia rheumatica: revisiting the concept of the disease. Rheumatology (Oxford). 2017 Apr 1;56(4):506-515. Clayton SA et al. Mitochondria as Key Players in the Pathogenesis and Treatment of Rheumatoid Arthritis. Front Immunol. 2021 Apr 29;12:673916. Barrera MJ et al. Dysfunctional mitochondria as critical players in the inflammation of autoimmune diseases: Potential role in Sjögren’s syndrome. Autoimmun Rev. 2021 Aug;20(8):102867. Becker YLC et al. Identification of Mitofusin 1 and Complement Component 1q Subcomponent Binding Protein as Mitochondrial Targets in Systemic Lupus Erythematosus. Arthritis Rheumatol. 2022 Jul;74(7):1193-1203. Acknowledgements: NIL. Disclosure of Interests Linda Johansson: None declared, Despina Michailidou Consultant of: Advisory Board fees from ChemoCentryx., Grant/research support from: NIH grant award #5T32HL007028-44., Solbritt Rantapää Dahlqvist: None declared, Christian Lood Consultant of: Advisory board for Redd Pharma., Grant/research support from: Receives research funding from Eli Lilly, Gilead Sciences, Boehringer Ingelheim, Redd Pharma, Amytryx, Horizon Pharma, Pfizer, and Bristol Meyers Squibb. Keywords: Vasculitis, Biomarkers DOI: 10.1136/annrheumdis-2023-eular.3983Citation: , volume 82, supplement 1, year 2023, page 1267Session: Vasculitis - aetiology, pathogenesis and animal models (Publication only)