Decreased myeloid dendritic cells indicate a poor prognosis in patients with severe fever with thrombocytopenia syndrome

Abstract

Objectives: Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerging infectious disease caused by a novel bunyavirus in which host immune system suppression is thought to be crucial in the development of disease. This study was designed to study the frequencies and activation status of dendritic cells (DCs) at different stages of SFTS and their association with disease severity. Methods: All confirmed SFTS patients (N = 115) were recruited from the Wuhan Union Hospital in 2015; routine laboratory parameters were collected. The frequencies, phenotypes, and subsets of circulating DCs, including myeloid and plasmacytoid dendritic cells (mDCs and pDCs), were analyzed by flow cytometry. Serum levels of interleukin (IL)-6, IL-10, and tumor necrosis factor alpha (TNF-α) were detected by ELISA. The laboratory parameters and other clinical events related to mortality were assessed by multivariate logistic regression analysis and receiver operating characteristic (ROC) curves. Results: The frequency of circulating mDCs, especially from day 9 after disease onset, could serve as a valuable prognostic biomarker for the outcome in SFTS patients (area under the curve = 0.929, p < 0.0001). In addition, persistent down-regulation of the co-stimulatory molecules CD80/CD86 on the mDCs was observed during the disease process. Moreover, levels of mDCs were inversely correlated with the production of IL-6, IL-10, and TNF-α and with viral load at admission. Conclusions: The present results indicate that DCs might be functionally impaired in SFTS. A decreased level of circulating mDCs was closely correlated with the severity of SFTS.

Keywords

• Severe fever with thrombocytopenia syndrome
• Acute phase
• Mortality
• Dendritic cell
• Prognosis