OP0097 Stimulated monocyte-derived macrophages from patients with enthesitis related arthritis secrete higher levels of il23 and lower levels of interferon gamma compared to healthy controls
Authors: C Fisher, D. Eleftheriou, D. Sen, Y. Ioannou
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Enthesitis related arthritis (ERA) is the subtype of juvenile idiopathic arthritis most closely related to adult spondyloarthropathy (SpA). Macrophages, the IL23/IL17 pathway and dysregulation of IFNγ are strongly implicated in the pathogenesis of adult SpA but remain relatively unexplored in ERA. <h3>Objectives</h3> To compare levels of IL23 and IFNγ produced by monocyte-derived macrophages (MDMs) in the presence of lipopolysaccharide (LPS) from patients with ERA compared to healthy controls. The effect of clinical features such as enthesitis, peripheral and axial arthritis on IL23 and IFNγ expression was also studied. <h3>Methods</h3> Peripheral blood monocytes from 39 patients (68% HLA B27 positive, 84% male, median age 16 years 4 months, median disease duration 3 years 10 months) and 21 age and gender-matched healthy controls were differentiated <i>in vitro</i> with macrophage-colony stimulating factor in to macrophages. Differentiated cells were treated with IFNγ for 24 hours to upregulate HLA B after which the cells were washed and stimulated with LPS (50 ng/mL). IL23 and IFNγ expression from the cell culture supernatants were measured by ELISA and luminex assay respectively. <h3>Results</h3> IL23 expression was significantly higher in patients with ERA [median 53580 pg/mL (IQR 35735–83945 pg/mL) vs 32110 pg/mL (IQR 13745–48235 pg/mL), p=0.01], particularly in patients who were HLA B27 positive [median 64650 pg/mL (IQR 36400–99650 pg/mL), p=0.0067]. IL23 was not significantly different between patients with and without peripheral arthritis or axial arthritis. However, patients who had active enthesitis (assessed clinically or on scan within 6 months of the sample) had significantly higher IL23 expression compared to patients without enthesitis [median 75905 pg/mL (IQR 36728–99425 pg/mL vs 38485 pg/mL (IQR 29923–63725 pg/mL, p=0.014] and healthy controls [p=0.0017]. Interestingly, patients who had both HLA B27 and active enthesitis had even higher levels of IL23 [median 79380 pg/mL (IQR 36540–103200 pg/mL), p=0.0018]. Conversely, levels of IFNγ were found to be lower from MDMs of patients with ERA compared to healthy controls, at baseline [median 3985 pg/mL (IQR 2820–6849 pg/mL) vs 6305 pg/mL (IQR 3938–8744 pg/mL), p=0.0054] and after LPS stimulation [median 9146 pg/mL (IQR 7438–11255 pg/mL) vs 11693 pg/mL (IQR 9481–13435 pg/mL), p=0.013]. No difference was found between patients who were HLA B27 positive and negative, although there was a trend towards lower levels of IFNγ in patients with enthesitis, this was not statistically significant. <h3>Conclusions</h3> IL23 expression is significantly higher from stimulated MDMs of patients with ERA compared to healthy controls, especially in HLA B27 positive patients with active enthesitis. This suggests a role for IL23 in the pathogenesis of ERA and supports the hypothesis that this sub-population of patients might benefit from IL23 blockade. Interestingly, IFNγ expression is lower in patients with ERA. Dysregulation of IFNγ has been shown to cause upregulation of the IL23/17 pathway in animal models<sup>1</sup> and thus may also contribute to the pathogenesis of ERA. <h3>Reference</h3> [1] Chu CQ, Swart D, Alcorn D, Tocker J, Elkon KB. Interferon-gamma regulates susceptibility to collagen-induced arthritis through suppression of interleukin-17. Arthritis Rheum2007Apr;56(4):1145–51. <h3>Disclosure of Interest</h3> None declared