PS1486 INTERLEUKIN‐33 IN PEDIATRIC PATIENTS WITH IMMUNE THROMBOCYTOPENIA: RELATION TO PROGNOSIS AND TREATMENT OUTCOME

Abstract

Background:The pathogenesis of thrombocytopenia in immune thrombocytopenia (ITP) has shifted from the traditional view of increased platelet destruction mediated by autoantibodies to more complex mechanisms where both impaired platelet production and T‐cell‐mediated effects play a role. Interleukin‐33 (IL‐33) is a newly identified cytokine of the IL‐1 family. There is increasing evidence to suggest that IL‐33 is a key inflammatory mediator in a complex network of immune cells and non‐immune cells. IL‐33 signals via its ST2 receptor and is involved in several autoimmune diseases by regulating T cell immune responses.Aims:To assess the level of IL‐33 in children and adolescents with ITP and correlate it with disease severity, treatment response and outcome.Methods:Fifty young patients with ITP were compared with 40 age‐ and sex‐matched healthy controls. Patients were studied stressing on bleeding manifestations, organomegaly/lymphadenopathy and therapy. Bleeding score was calculated to each patient according to the ITP Bleeding Scale (IBLS). The studied ITP Patients were further classified into 3 subgroups: “newly diagnosed ITP” (ITP within 3 months from diagnosis), “persistent ITP” (ongoing ITP between 3 and 12 months from diagnosis), and “chronic ITP” (ITP lasting more than 12 months). ITP Patients were also classified into active ITP defined as platelet count below 100 x 109/L accompanying with or without bleeding episode or complete response (CR) which was defined as any platelet count of at least 100 × 109/L and absence of bleeding.Results:IL‐33 levels were significantly lower in ITP patients than controls (median [IQR], 150 [100 – 230] versus 210 [180–260] pg/mL; p = 0.011). Levels were also lower in chronic than newly diagnosed ITP. IL‐33 levels are lower among active ITP (median [IQR], 105 [85 – 120] pg/mL) compared with those in complete remission (median [IQR], 240 [200 – 250] pg/mL) and healthy controls (p < 0.001) while no significant difference was found among the two latter groups (p = 0.197). Patients who had splenectomy had lower IL‐33 levels than non‐splenectomized ones. Lower IL‐33 levels were found among patients with corticosteroid‐dependence and relapse (p < 0.05). No significant difference as regards IL‐33 between treated and un‐treated patients with active ITP. IL‐33 was positively correlated to platelet count at sampling (r = 0.714, p < 0.001).Summary/Conclusion:Conclusions: Alterations of IL‐33 levels in pediatric patients with ITP highlight the role of T‐cell immune response in the pathogenesis of ITP. It may be considered as a potential prognostic marker for the development of chronic ITP as it correlates with disease activity. Further studies investigating the role of IL‐33 in the pathogenesis of ITP may provide a new therapeutic target for ITP.