Furin mRNA expression in peripheral blood correlates with chronic hepatitis B virus infection.
OBJECTIVE
The mechanisms underlying development of chronic hepatitis B virus (HBV) infection are related to immune tolerance, but are as yet incompletely understood. Furin has been found to be essential for maintenance of peripheral immune tolerance mediated by regulatory T cells (Treg). Such effect of furin on chronic HBV infection was investigated in this study.


METHODS
Peripheral blood from 40 individuals with self-limited HBV infection, 40 patients with asymptomatic persistent HBV infection and 40 patients with chronic hepatitis B (CHB) was collected and mRNA expression levels of furin, transforming growth factor (TGF)-β1 and the Treg-function-related forkhead transcription factor FoxP3 were detected using quantitative real-time polymerase chain reaction. CD4(+) CD25(+) FoxP3(+)  Treg were detected using flow cytometry.


RESULTS
Furin mRNA expression in peripheral blood was significantly higher in patients with persistent HBV infection than in individuals with self-limited infection (P < 0.01), and was much higher in CHB patients than in those with asymptomatic persistent infection (P < 0.01). Furthermore, furin mRNA was relatively higher in patients with positive hepatitis B e antigen and higher levels of serum HBV DNA (>10 000 copies/mL). In patients with CHB, furin mRNA expression was found to correlate with TGF-β1 mRNA and FoxP3 mRNA expression using Spearman's rank correlation coefficient test. It was 5.7-times higher in CD4(+) CD25(+)  T cells than in CD4(+) CD25(-)  T cells and correlated with the frequency of Treg (P < 0.05).


CONCLUSIONS
Furin mRNA expression in peripheral blood correlates with chronic HBV infection and liver damage, and seems to participate in immune inhibitory and anti-inflammatory mechanisms in HBV infection, mediated by TGF-β1 and/or Treg.
Hepatology Laboratory, Hospital for Liver Disease             Department of Infectious Diseases, Third Affiliated Hospital, Sun Yat-Sen University             Liver Disease Key Laboratory of Guangdong Province, Guangzhou, Guangdong             Department of Infectious Diseases, First Affiliated Hospital of Nanhua University, Hengyang, Hunan, China.
Yan
Y
Chen
Xia
X
Xie
Lin
L
Gu
Xiao-Hui
XH
Huang
Xiao-Mou
XM
Peng