S849 TNF‐α BLOCKADE CORRECTS THE MONOCYTE/MACROPHAGE IMBALANCE IN PRIMARY IMMUNE THROMBOCYTOPENIA (ITP)

Abstract

Background:Primary immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder. Deviation of monocyte/macrophage subsets plays an important role in the pathogenesis of ITP. TNF‐α blockade is widely used in many autoimmune diseases with satisfactory effects. However, the effect of TNF‐α blockade on monocyte/macrophage system in ITP remains unknown.Aims:Our study aimed to investigate whether TNF‐α could restore the disturbed balance of monocyte/macrophage subsets and be a potential therapeutic strategy for ITP.Methods:Plasma TNF‐α was detected by ELISA. The monocyte/macrophage subsets were analyzed using flow cytometry and immune fluorescence. Macrophage polarization was analyzed using western blot, q‐PCR, and flow cytometry. Phagocytic capacity of macrophages was measured by the engulfment of opsonized platelets. T‐cell priming ability of macrophages was determined through co‐culturing with CD4+ T cells and CD8+ T cells. We established a passive model of murine ITP. Platelet count was measured every other day. The retention of platelets in liver and spleen was assessed by the fluorescence intensity detected using the in vivo imaging system.Results:ITP patients manifested with an increased TNF‐α expression which was inversely correlated with platelet count. Moreover, the numbers of TNF‐α‐expressing macrophages in spleen and CD16+ monocytes were more than that of healthy controls. TNF‐α blockade inhibited M1 macrophage polarization by suppressing the NF‐κB signaling pathway, and dampened the phagocytic capacity and T‐cell priming ability of macrophages. Moreover, anti‐TNF‐α therapy reduced the number of non‐classical monocytes and M1 macrophages, ameliorated the retention of platelets in spleen and liver, and significantly increased the platelet count of ITP mice.Summary/Conclusion:Our study demonstrated that TNF‐α blockade could decrease the number and functions of pro‐inflammatory subsets of monocytes/macrophages by inhibiting NF‐κB signaling pathway, leading to remarkable attenuation of antibody‐mediated platelet destruction both in vitro and in vivo, thus might be a promising therapeutic strategy for the management of ITP.image