Dynamic Changes and Differences of B-cell Responses between Severe Dengue Disease and Mild Dengue Fever / 中山大学学报(医学科学版)

ABSTRACT

@#【Objective】 To find out the possible marker for early warning or therapeutic target of severe dengue disease ，we studied B cell responses during natural dengue virus（DENV）infection and their association with disease severity.【Methods】Sixty-two cases and their blood samples were collected from the patients hospitalized during September to December in 2014 and three groups were designated as mild dengue（DF，n=33），severe dengue（SD，n=29）and control group（Control ，n=6）. Multicolor flow cytometrywas used to analyze the dynamic changes of B cells and plasmablasts in the peripheral blood of patients during the acute phase and the critical phase. The plasmablasts in a succession of samplesfrom the same infected patients （including 3 mild and 3 severe cases） were further analyzed. We also observed the changes of B cells and their subsets ，including naive B cells ，memory B cells and plasmablasts，during primary and secondary infections. 【Results】 The expansion of B cells in the severe group was significantly higher than that in the mild group（P=0.013），especially on day 5 and day 6 after the symptom onset（P = 0.017 and 0.002，respectively）. Compared with those in the control group，the plasmablasts in the mild and severe groups showed significant proliferation（P=0.011 and 0.032，respectively），but no statistical difference was observed between these two groups. The analysis of the serial blood samples showed that the plasmablasts，in mild cases，peaked on day 7 and 8 and returned to baseline on day 10，whereas in the severe group，peaked on day 7 to 9，and still existed at a certain rate after day 10. In mild dengue group，more proliferative B cells，less naive B cells and memory B cells were found in secondary infection than in primary infection（P = 0.028，0.010 and 0.037，respectively），but plasmablasts revealed no difference. In severe dengue group， only naïve B cells significantly decreased in secondary infection （P = 0.018）. 【Conclusion】 B cell responses between mild and severe dengue after DENV- 1 infection present different trends. The significant proliferation of B cells in the early stage of the disease and the persistent existence of plasmablasts may be related to the severity of the dengue disease.