Elevation of human leukocyte antigen-G expression is associated with the severe encephalitis associated with neurogenic pulmonary edema caused by Enterovirus 71

Abstract

Enterovirus 71 (EV71) infection can develop devastating clinical outcomes such as brain stem encephalitis (BE) and pulmonary edema (PE). Alteration of human leukocyte antigen-G (HLA-G) expression or cytokine production was considered playing important roles in virus-related pathogenesis. However, clinical relevance of HLA-G in EV71 infection remains unknown. In the current study, patients were stratified by disease severity as BE (n=107) and PE (n=18). HLA-G expression on peripheral blood monocytes from patients with BE (n=15), patients with PE (n=15) and control subjects (n=31) was analyzed with flow cytometry. Plasma soluble HLA-G (sHLA-G) (in 67 BE, 18 PE and 120 control subjects), IL-6 and IL-10 (in 50 patients with BE, 18 patients with PE and 45 control subjects) were determined with enzyme-linked immunosorbent assay. Data showed that the percentage of HLA-G-positive monocytes (mean 7.76 vs 3.68%, p<0.001), levels for sHLA-G (median 129.2 vs 70.6U/ml, p<0.001), IL-10 (median 160.5 vs 29.5pg/ml, p<0.001) and IL-6 (median 20.50 vs 5.21pg/ml, p=0.002) was significantly higher in patients with PE than in patients with BE. Taken together, our findings indicated that elevation of HLA-G expression on monocytes, plasma sHLA-G, IL-10 and IL-6 levels was associated with PE in patients infected with EV71.