https://www.selleckchem.com/products/z-4-hydroxytamoxifen.html 998, (95%CI 0.992-1.000). TNF inhibitors treatment could restore the equilibrium of 21 metabolites. The most involved pathways in AS were amino acid biosynthesis, glycolysis, glutaminolysis, fatty acids biosynthesis and choline metabolism. This study characterized the serum metabolomics signatures of AS and TNF inhibitor therapy. We developed a five-metabolites-based panel serving as a diagnostic tool to separate patients from HCs. This serum metabolomics study yielded new knowledge about the AS pathogenesis and the systemic effects of TNF inhibitors.Cytotoxic T lymphocytes (CTLs)-mediated platelet destruction plays an important role in the pathogenesis of primary immune thrombocytopenia (ITP). The programmed cell death protein 1 (PD-1) signaling can turn off autoreactive T cells and induce peripheral tolerance. Herein, we found that the expression of PD-1 and its ligand PD-L1 on CD8+ T cells from ITP patients was decreased. Activating PD-1 pathway by PD-L1-Fc fusion protein inhibited CTLs-mediated platelet destruction in ITP in vitro. PD-1 promoter hypermethylation in CD8+ T cells was found in ITP patients, resulting in decreased PD-1 expression. The demethylating agent decitabine at a low dose was proved to restore the methylation level and expression of PD-1 on CD8+ T cells and reduce the cytotoxicity of CTLs of ITP patients. The phosphorylation levels of phosphatidylinositol 3-kinase (PI3K) and AKT in CD8+ T cells were significantly downregulated by low-dose decitabine. Furthermore, blocking PD-1 could counteract the effect of low-dose decitabine on CTLs from ITP patients. Therefore, our data suggest that the aberrant PD-1/PD-L1 pathway is involved in the pathophysiology of ITP and enhancing PD-1/PD-L1 signaling is a promising therapeutic approach for ITP management. Our results reveal the immunomodulatory mechanism of low-dose decitabine in ITP by inhibiting CTLs cytotoxicity to autologous platelets