The Expression And Significance Of Myeloid-derived Suppressor Cells In The Peripheral Blood Of Patients With Severe Fever With Thrombocytopenia Syndrome

Purposes Severe fever with thrombocytopenia syndrome(SFTS) is a new emerging infectious disease caused by a novel Bunyavirus. Acute fever, respiratory or gastrointestinal symptoms may be the main clinical presentation of SFTS. The most common abnormalities in laboratory test results are thrombocytopenia, leukocytopenia, and elevated levels of serum enzymes. Severe SFTS patients can quickly progress to multiple organ dysfunction even death. The exact mechanism of SFTSV pathogenesis remains unclear but it is generally suspected that immunopathology plays a key role. Myeloid-derived suppressor cells(MDSCs) are a heterogeneous population of cells that derive from bone marrow, which could differentiate into mature granulocytes, macrophages or dendritic cells(DCs). The suppressive activity of MDSCs contributes to the negative regulation of immune responses. Due to the heterogeneity of MDSCs, there are not specific markers to define these cells in human. CD15+ granulocytic(G-MDSCs) and CD14+ monocytic MDSCs(M-MDSCs) have been reported to be the two main MDSC subtypes. Here we analyzed MDSC subsets in the in peripheral blood of SFTS patients, and their possible relationship with the disease severity of SFTS.Methods The 40 confirmed SFTS patients and 18 healthy controls were included in our study. All these patients were admitted to the department of infectious diseases of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between May 2014 and September 2015. According to the disease severity, SFTS patients were divided into 2 groups, namely severe cases group and non-severe cases group. Clinical data and key lab test results were collected in this study. Peripheral blood samples from 20 severe and 20 non-severe SFTS patients were collected to explore myeloid-derived suppressor cells(MDSCs) subsets levels and proportion of immune cells by flow cytometric analysis; serum levels of G-CSF in severe cases and non-severe cases were measured using enzyme-linked immunosorbent assays.Results Granulocytic myeloid-derived suppressor cells(G-MDSCs) levels were significantly higher in SFTS patients than in healthy controls; when compared with non-severe cases, G-MDSCs were markedly increased in severe cases. Correlations between the G-MDSCs levels and immune cells showed G-MDSCs levels were negatively associated with the percentage of cytotoxic T cells(CTL), while positively correlated with the percentage of natural killer(NK) cells. And G-MDSCs levels were found to be positively associated with SFTS viral loads. Serum concentration of G-CSF was increased in severe cases than in non-severe cases. The levels of G-CSF were 387.9±144.1pg/m L and 788.3±349.1pg/m L in non-severe cases and severe cases separately. The difference was significant(p<0.01).Conclusions Proportion of G-MDSCs were significantly increased in SFTS, but proportion of M-MDSCs were nearly normal, which predicting that G-MDSCs may be the predominant cells of MDSCs subsets to depress the immunofunction of SFTS. G-MDSCs may be associated with disease severity of SFTS by suppressing the cytotoxic T cells expansion and immunofunction of NK cells. The increased concentration of serum G-CSF indicated that they may play a role in activating MDSCs and promoting MDSCs to gather in peripheral blood.