IL-18 and IL-18 binding protein are related to severity of myelodysplastic syndromes

Abstract

Abstract Background Myelodysplastic syndromes (MDS) was defined as a clonal hematopoietic disorder disease. Although current stratified therapy for MDS has greatly improved overall survival, there is still a subset of them who suffered from progression to AML with a poor prognosis. Immune factors play essential roles in the pathogenesis and evolution of MDS. It is known that the level of plasma IL-18 which has anti-tumor and immunomodulatory effects increased in MDS patients. Recent research found that the presence of IL-18 binding protein(IL-18BP) depresses its effect. In this study, we intended to discuss the importance of IL-18 and IL-18BP on the severity of MDS and the potential mechanisms affecting the efficacy and explore new targets for MDS further therapy. Methods 43 MDS patients, 14 AML patients, and 16 healthy volunteers were enrolled in our study. The levels of IL-18, IL-18BP of bone marrow supernatant were tested by ELISA and clinical information was collected. The expression of perforin, granzyme B, and IFN-γ, as well as PD-1 and TIM-3 expression on the surface CD8 + T and NK cells, was tested in MDS patients by flow cytometry, and correlations among all these data were analyzed by SPSS. Results We found that the levels of IL-18, IL-18BP, and free IL-18 (fIL-18) in the bone marrow supernatants of both MDS and AML were higher than those of healthy controls. FIL-18 were negatively correlated with the severity of MDS. CD8 + T cells in MDS were hypofunctional, with a lower secretion of perforin, granzyme B, and IFN-γ than in healthy controls. The level of fIL-18 was positively correlated with perforin and IFN-γ; the expression of IL-18Rα on the surface of CD8 + T cells was low in MDS patients. The expression of IL-18Rα was negatively correlated with perforin, granzyme B, and IFN-γ. In addition, elevated levels of PD-1 and TIM-3 on the surface of CD8 + T cells in MDS seemed no significant correlation with fIL-18 and IL-18BP. Conclusion MDS is in a state of immunosuppression as evidenced by the decreased number and depressed function of CD8 + T cells and NK cells. Increased expression of fIL-18 in MDS patients was shown, compared to healthy controls. Due to the presence of IL-18BP, fIL-18 is relatively insufficient. Thus antagonizing IL-18BP is a promising new target for MDS.