SAT0030 Active PMR and GCA Is Associated with Changes in Monocyte Subset Composition. (15th July 2016) - Wang, Q.
Abstract : Background: Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are two closely related syndromes affecting older people. Pro-inflammatory cytokine IL-6 is found increased in both GCA/PMR patients and in the aged healthy population [1]. Pro-inflammatory monocytes, identified by CD16 and CD14 expression, increase with age and are potent producers of IL-6 [2]. Importantly, monocyte-derived macrophages have been identified in the inflamed arteries of GCA and contribute to the immunopathology of GCA [3]. Yet, peripheral monocyte subsets are less well studied in GCA and PMR patients. Objectives: To assess the distribution of different monocyte subsets in newly diagnosed GCA and PMR patients before and after glucocorticoid (GC) treatment as well as the presence of CD16+ monocytes/macrophages in GCA temporal artery biopsies. Methods: Peripheral blood samples of 24 newly-diagnosed GCA patients, 22 newly-diagnosed PMR patients and 24 age-matched, healthy controls (HCs) were studied. In a prospective, longitudinal study design, samples were obtained from 17 GCA and 15 PMR patients who were in remission after 3 month of treatment with GCs. Absolute numbers of total monocytes and non-classical (CD14 dim CD16 bright ), intermediate (CD14 bright CD16 dim ) and classical (CD14 bright CD16 – ) monocytes were determined by truecount and flow cytometry. Immunohistochemical staining for detection of CD16 and CD68 was performed on sections of TAB from 15 GCA patients. Co-localization of CD16 and CD68 cells was performed using immunofluorescence. Results: Total numbers of circulating monocytes were increased in newly-diagnosed GCA and PMR patients compared to age-matched HCs. Following 3 months of GC treatment, monocyte numbers normalized in PMR patients. When analysing absolute numbers of non-classical, intermediate and classical monocytes, we found the classical monocytes increased in newly-diagnosed GCA and PMR. GC treatment in GCA and PMR decreased numbers of non-classical and intermediate monocytes but not classical monocytes. CD16 + cells were readily identified in GCA TABs. CD16 staining was detected in macrophage rich area's as evidenced by CD68 staining. Double Immunofluorescence using CD16 and CD68 showed the presence of double positive CD16+ CD68+ macrophages in GCA lesional tissue. Conclusions: We show that peripheral monocyte numbers are modulated in active GCA and PMR. Treatment with GCs decreased CD16+ monocytes in GCA/PMR. CD16+ macrophages were readily detected in inflamed temporal artery biopsy tissue. The data may suggest a role for CD16+ monocytes in the pathogenesis of GCA/PMR. References: van der Geest K.S.M, et al. "Serum markers associated with disease activity in giant cell arteritis and polymyalgia rheumatica." Rheumatology (2015) Nyugen J., et al. "Impaired functions of peripheral blood monocyte subpopulations in aged humans." Journal of clinical immunology 30.6 (2010): 806–813 Rittner H.L., et al: Tissue-destructive macrophages in giant cell arteritis. Circulation research 1999, 84(9):1050–1058 Disclosure of Interest: None declared