IL-18 and IL-18 Binding Protein Are Related to Disease Severity of Myelodysplastic Syndromes

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-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, correlations among all these data were analyzed by SPSS.

Results: We found that the levels of IL-18, IL-18BP, and 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-18is relatively insufficient. Thus antagonizing IL-18BP is a promising new target for MDS.

No relevant conflicts of interest to declare.