OP0062 CYTOKINE PRODUCING B CELLS SKEW MACROPHAGES TOWARDS A PRO-INFLAMMATORY PHENOTYPE IN GIANT CELL ARTERITIS

Background: Giant cell arteritis (GCA) is the most frequent form of systemic vasculitis affecting temporal artery (TA) and aorta. Macrophages T cells are well recognized players in pathogenesis GCA while B often not taken into account. Recently, changes circulating compartment were documented found to organize tertiary lymphoid organs at site vascular inflammation (TA aorta). 1,2 The exact role still unknown as no disease-specific antibodies have been defined. However, beside their humoral immunity, can also produce various cytokines. In GCA, peripheral treated patients, showed an enhanced capacity pro-inflammatory cytokine Interleukin (IL)6 3 which nowadays important target treatment GCA. 4 We hypothesize that help shape inflammatory response by producing effector regulatory Objectives: aimed assess profile lesional studied effects on macrophage skewing. Methods: To with cytokines, cryopreserved blood mononuclear 11 untreated patients 15 age- sex-matched healthy controls (HC) cultured for days presence CpG-ODN 2006. During last 5 hours phorbol myristate acetate Calcium Ionophore added. Thereafter, intracellular (IL6, TNFa, IFNy, LTb) cell-related cytokines (IL10) measured flow cytometry. potential skewing macrophages products, THP-1 differentiated stimulated 24 supernatant from (n=6). Expression IL23, IL6, IL1b, MMP9 YKL40 was assessed mRNA level qPCR. local production, TA (n=11) aorta tissue samples (n=10) histologically-proven stained detect CD20, LTb, IL10 expression. For comparison, 14 tissues atherosclerosis-related aortic aneurysm included. Results: vitro percentage IL6+ (median (IQR); 44 (41-52)) IL6+TNFa+ (12 (8-24)) compared HC (IL6+: 28 (23-39), IL6+TNFa+: 6 (4-24)). addition, soluble factors, secreted derived cells, skewed towards a phenotype expression TNFa. Furthermore, these higher remodelling factor pro-angiogenic YKL40. At inflammation, detected regions clear IFNY, LTb both patients. Conclusion: This study demonstrates express (IL6 TNFa) influence other cellular Specifically, factors able skew phenotype. this provides evidence active shaping milieu thereby revealing new intervention References: [1]Ciccia, F. et al. Ectopic CXCL13, BAFF, April LT-? associated giant arteritis. Ann. Rheum. Dis. 76 , 235–243 (2017) [2]Graver, JC. Massive Infiltration Organization Into Artery Tertiary Lymphoid Organs Aorta Large Vessel Cell Arteritis. Front. Immunol. 10 83 (2019) [3]Van Der Geest, KSM. Disturbed homeostasis newly diagnosed polymyalgia rheumatica. Arthritis Rheumatol. 66 1927–1938 (2014) [4]Stone, JH. Trial tocilizumab giant-cell N. Engl. J. Med. 377 317–328 Disclosure Interests: Jacoba Carolien Graver: None declared, William Febry Jiemy: Dania Altulea: Annemieke Boots Consultant of: Grunenthal, Peter Heeringa: Wayel Abdulahad: Elisabeth Brouwer Speakers bureau: Roche, fees paid UMCG, Maria Sandovici: declared