AB0041 Serum Amyloid A Stimulates The Induction of Inflammatory Mediators in Monocytes from Behçet's Disease Patients: A Proof of Concept Study. (15th July 2016) - Lopalco, G.
Abstract : Background: Behcet's disease (BD) is a complex inflammatory disorder characterised by an abnormal innate and adaptive immune response leading to hyper-activation of pro-inflammatory mediators. Recurrent oral aphthous, genital ulcers and chronic relapsing bilateral uveitis are the hallmarks of the disease. Serum amyloid-A (SAA) is a biomarker of inflammation recently associated to BD, and pro-inflammatory stimuli including IL-6, IL-1 and TNF are known to be involved in the SAA production. Moreover, several innate immune cells such as neutrophils, monocytes and macrophages have been reported to produce pro-inflammatory cytokines also through inflammasome activation after SAA stimulation. Objectives: The purpose of this study was to investigate the involvement of SAA in the pathogenesis of Behçet's disease Methods: Monocytes obtained from heparinised venous blood of Behçet's disease patients (BD, n=14) and healthy controls (HC, n=7) were stimulated or not with SAA, and serum cytokine levels of IL-1β, IL-18, IL-6 and TNF-α were analysed in the medium using a multiplex bead analysis. Statistical approaches included two-tailed Mann-Whitney test (for two non-parametric groups) and Student's t-test (for two parametric groups) were used for statistical comparisons between groups. Correlations were calculated using Spearman's correlation (two-tailed p-value) analysis. Results: BD monocytes showed an increased IL-1β (p=0.0017), TNF-α (p=0.0003) and IL-6 (p=0.0003) secretion after SAA stimulation. No differences were observed in the amounts of pro-inflammatory cytokines production between HC and BD. We also found that IL-1β levels positively correlated with IL-6 (r=0.842, p<0.001), and TNF-α (r=0.889, p<0.001), whilst TNF-α levels positively correlated with IL-6 (r=0.894, p<0.001) levels. Moreover, also IL-18 showed a positive trend with no significant differences between the two groups Conclusions: These findings suggest that SAA can promote inflammatory mediators production thereby contributing to the inflammatory manifestations typically observed in BD. References: Hatemi G, Yazici Y, Yazici H. Behçet's syndrome. Rheum Dis Clin North Am 2013; 39:245–611. Vitale A, Rigante D, Lopalco G, Brizi MG, Caso F, Franceschini R, Denaro R, Galeazzi M, Punzi L, Iannone F, Lapadula G, Simpatico A, Marrani E, Costa L, Cimaz R, Cantarini L. Serum amyloid-A in Behçet's disease. Clin Rheumatol. 2014. Lopalco G, Lucherini OM, Vitale A, Talarico R, Lopalco A, Galeazzi M, Lapadula G, Cantarini L, Iannone F. Putative Role of Serum Amyloid-A and Proinflammatory Cytokines as Biomarkers for Behcet's Disease. Medicine (Baltimore). 2015 Oct;94(42):e1858. Uhlar CM, Grehan S, Steel DM, Steinkasserer A, Whitehead AS. Use of the acute phase serum amyloid A2 (SAA2) gene promoter in the analysis of pro- and anti-inflammatory mediators: differential kinetics of SAA2 promoter induction by IL-1 beta and TNF-alpha compared to IL-6. J Immunol Methods 1997;203:123–30. Disclosure of Interest: None declared