Op0029 neutrophil Extracellular Traps in Giant Cell Arteritis Inflamed Temporal Arteries: Localization, Co-Expression of Inflammatory Cytokines and Association With Disease Extension

Abstract

Background:Giant cell arteritis (GCA) represents the most prevalent form of systemic vasculitis in elderly, characterized by a remarkable heterogeneity in terms of clinical and histological phenotype, the pathogenetic mechanisms and treatment selection (1). An interplay between cells of both innate and adaptive immunity, appear to govern the pathophysiologic mechanisms (2). Among the different cellular populations, neutrophils may hold a central role in GCA pathogenesis, since they are present in abundance in tissue injury (3,4). Most importantly, they are a source of neutrophil extracellular traps (NETs) that may deliver immunocompetent substances, necessary for the perpetuation of the inflammatory response (5). The detection and function of NETs have not been studied in GCA.Objectives:To explore the presence and clinical significance of NETs in temporal artery biopsies (TABs) of patients with GCA.Methods:Ten patients with GCA [5 with limited cranial vasculitis (CV) and 5 with associated generalized large vessel vasculitis (LVV), as defined by 18F-fluorodeoxyglucose (FDG) positron-emission tomography with computed tomography (PET/CT)] and 8 patients with polymyalgia rheumatica (PMR) were studied. GCA and PMR patients fulfilled the 1990 ACR and 2012 EULAR/ACR provisional classification criteria, respectively. The presence, location, quantitation and decoration of NETs with IL-6, IL-1β, and IL-17A were assessed in TABs at the time of disease diagnosis by tissue immunofluorescence and confocal microscopy. Quantification of NETs in tissue sections was performed using the Imaris v.9.3 software that counts the total measure volume instead of only the projection area (6). Serum levels of IL-6 and IL-17A around the time of tissue biopsy were also evaluated in all patients.Results:All temporal artery biopsies from GCA patients had NETs located mainly in the adventitia, adjacent to the vasa vasorum, whereas TABs from PMR patients had no NET structures. LVV was associated with a higher NETs to total tissue volume ratio, compared to CV-GCA [p=0.0317]. NETs decorated with IL-6 were present in TABs of all LVV and 3 of 5 CV-GCA patients, while IL-17A positive NETs were observed in all GCA patients. IL-1β-positive NETs were not detected in any GCA patient. No relation was found between serum IL-6 and IL17A levels and NETs containing IL-6 and/or IL-17A.Conclusion:NETs bearing IL-6 and IL-17A cytokines are present in inflamed GCA-TABs. IL-6 positive NETs are associated with the LVV phenotype and might be useful as a tissue biomarker for disease severity and extent.References:[1]K. S. M. van der Geest et al. Arthritis Rheumatol, 2018;70:1366-76.[2]C. Salvarani et al. Lancet, 2008;372:234-45.[3]D. Chatelain et al. Ann Rheum Dis, 2009;68:84-8.[4]S. Nadkarni et al. Circ Res, 2014;114:242-8.[5]V. Mutua et al. Clin Rev Allergy Immunol, 2020.[6]S. V. Costes et al. Biophys J, 2004;86:3993-4003.Disclosure of Interests:None declared