POLYARTICULAR JIA HAS A DISTINCT CO-INHIBITOR RECEPTOR PROFILE AMONG OTHER JIA SUBTYPES

BackgroundJuvenile idiopathic arthritis (JIA) is the most common inflammatory joint disease in children, driven by continuous T-cell activation.[1] T cell activation is counter-balanced by signals generated by co-inhibitory receptors (co-IRs) such CTLA-4, PD-1, LAG-3, and TIM-3.[2]ObjectivesWe aimed to identify the role of co-IRs in the pathogenesis of different subtypes of JIA.MethodsIn total, we included 107 patients with oligoarticular JIA (n=67), polyarticular JIA (n=12), enthesitis related arthritis (n=17), systemic JIA (n=11) and healthy controls (HC, n=10). We collected plasma samples from the patients during the active phase of their disease. We measured the soluble plasma levels of co-IRs by commercial pre-defined cytometric bead array kits and their cellular expression by flow cytometry in blood mononuclear cells. We compared the plasma levels and cellular expressions of different coIRs within different JIA subgroups.ResultsIL-2 levels were lower than HC in all JIA subgroups. The polyarticular JIA group distinguished from the four different JIA subgroups, by having different co-IR pattern. In this specific subgroup, CTLA4, PD-1 and 4-1BB levels were higher than other groups. Polyarticular JIA is the more chronic and severe form of JIA, especially when compared to oligoarticular JIA. (Figure 1).Figure 1.We investigated the correlations between disease activity markers and plasma co-IRs. Plasma TIM3 levels correlated with erythrocyte sedimentation rate, C-reactive proteins and JADAS in the polyarticular JIA group. In oligoarticular JIA group, JADASs correlated with plasma PD-1 levels, C-reactive protein with PD-L1 plasma levels. Erythrocyte sedimentation rates correlated with IL-2, CD86, PD-L1 and PD-1 plasma levels. There was no correlation between disease activity markers and co-IRs levels in the systemic JIA group and enthesitis related arthritis group.Finally, we analysed the cellular surface expression of different co-IRs on the PBMCs of different JIA subtypes. Similar to plasma levels, both the percentage and the MFI (mean fluorescence intensity) of CTLA4 expression was higher in polyarticular JIA subgroup.ConclusionThis is the first report studying the effects of different co-IRs in different subtypes of JIA. Polyarticular JIA patients had a different coIR profile, having more CTLA-4, PD-1 and 4-1BB in their plasma than the other subtypes of JIAReferences[1]Wedderburn, L.R., et al., Int Immunol, 2001. 13(12): p. 1541-50.[2]Wherry, E.J. and M. Kurachi, Nat Rev Immunol, 2015. 15(8): p. 486-99.AcknowledgementsThis work was supported by a research grant from FOREUM Foundation for Research in RheumatologyDisclosure of InterestsNone declared