POS0114 ABERRANT MONOCYTE SUBSETS IN PATIENTS WITH BEHÇET’S DISEASE
Authors: C. Li, J. Liu, H. Chen, W. Zheng
Journal: Annals of the Rheumatic Diseases (2021)

Background: Behçet’s Disease (BD) is a systemic vasculitis of unknown etiology[1]. Monocytes closely related to inflammation potentially contribute to BD’s pathogenesis. They are classified into three subsets: classical monocytes (CM), intermediate monocytes (IM) and non-classical monocytes (NCM). Abnormalities of monocyte subsets have been reported in many infectious, inflammatory and autoimmune diseases[2-6], but their implication in BD remains elusive. Objectives: To investigate the distribution, phenotypes and functions of monocyte subsets in BD and explore their roles in BD pathogenesis. Methods: The frequencies and phenotypes of monocyte subsets in BD and healthy controls (HC) were determined by flow cytometry, and their correlation with clinical parameters was analyzed. Intracellular cytokines and phosphorylated signal proteins [phosphorylated p65(p-p65) and phosphorylated p38(p-p38)] were determined in LPS-activated monocyte subsets by flow cytometry. Monocyte subsets of BD and HC were sorted and co-cultured with naïve CD4 + T cells, and Th1 cell frequencies were measured on day 5. Results: A higher IM (9.0±3.6 % vs. 4.5±2.0%, p&lt;0.01) and lower NCM (2.6±1.2% vs. 4.2±2.0%, p&lt;0.01) population in BD patients were noted. BD IM were positively correlated with CRP (r=0.5456, p&lt;0.05), ESR (r=0.4683, p=0.05), and the serum level of TNF-a (r=0.7372, p&lt;0.001) and IL-6(r=0.5013, p&lt;0.05). BD NCM were negatively correlated with CRP (r=0.4822, p&lt;0.05) and the serum level of IgM (r=-0.7830, p&lt;0.001). Moreover, BD IM decreased (12.3±3.8% vs. 5.7±3.6%, p&lt;0.05), while BD NCM increased (2.6±1.3% vs. 3.5±1.5%, p&lt;0.01) after BD patients achieved remission. CD11b and CD64 expression on CM, IM and NCM in BD were enhanced. BD CM promoted TNF-a (61.0±11.4% vs 48.3±9.9%, p&lt;0.05) and IL-6 (7.2±5.4% vs1.9±1.7%, p&lt;0.05) production and facilitated Th1 differentiation. BD IM promoted IL-6 production (6.2±3.8% vs 2.6±1.6%, p&lt;0.05). Furthermore, we demonstrated a higher level of p-p65 (12.8±2.9% vs 3.3±1.1%, p&lt;0.01) in BD CM and increased p-p65 (3.2±0.6% vs 0.01±0.01%, p&lt;0.01) and p-p38 (1.1±0.6% vs 0.03±0.01%, p&lt;0.01) in BD IM. Conclusion: To our knowledge, our study is the first study on monocyte subsets in BD. Our data highlighted the aberrant populations of IM and CM in BD, potentially implicated in BD pathogenesis. References: [1]Ahmet, Gül, Pathogenesis of Behçet’s disease: autoinflammatory features and beyond, Semin. Immunopathol. 37 (2015) 413-418. [2]G.Fingerle, A.Pforte, B.Passlick, et al.The novel subset of CD14+/CD16+ blood monocytes is expanded in sepsis patients, Blood. 82 (1993) 3170-3176. [3]M.Moniuszko, A. Bodzenta-Lukaszyk, K. Kowal, et al. Enhanced frequencies of CD14++CD16+, but not CD14+CD16+, peripheral blood monocytes in severe asthmatic patients, Clin. Immunol. 130 (2009) 338-346. [4]M.D.Sanchez, Y.Garcia, C.Montes,et al.Functional and phenotypic changes in monocytes from patients with tuberculosis are reversed with treatment, Microbes. Infec. 8 (2006) 2492-2500. [5]S.Koch, T.Kucharzik, J.Heidemann,et al. Investigating the role of proinflammatory CD16+ monocytes in the pathogenesis of inflammatory bowel disease, Clin. Exp. Immunol. 161 (2010) 332-341. [6]H. Zhu, F. Hu, X. Sun,et al.CD16(+) Monocyte Subset Was Enriched and Functionally Exacerbated in Driving T-Cell Activation and B-Cell Response in Systemic Lupus Erythematosus, Front. immunol. 7 (2016) 512. Disclosure of Interests: None declared