Intrahepatic expression of programmed death-1 and its ligands in patients with HBV-related acute-on-chronic liver failure.
Hepatitis B virus (HBV) infection is a major public health problem, and HBV-related acute-on-chronic liver failure (HBV-ACLF) has an extremely poor prognosis due to a lack of understanding of pathogenesis as well as a lack of effective treatments. Signals from the inhibitory receptor programmed death-1 (PD-1) have been demonstrated to be involved in regulating the pathogenesis of infectious diseases. However, the expression of PD-1 and its ligands in HBV-ACLF patients has yet to be evaluated. In this study, the expression of PD-1 and its ligands, PD-L1 and PD-L2, in liver biopsies from HBV-ACLF as well as chronic hepatitis B (CHB) patients were analyzed by immunohistochemistry. The results showed that all three molecules were observed in the HBV-ACLF samples and their levels were significantly higher than they were in CHB. Immunofluorescence double-staining showed that PD-1 was found on CD3(+), CD8(+) T cells, CD56(+) NK cells, CD68(+) macrophages, CK-18(+) epithelial cells, and CD16(+) monocytes. The PD-L1 expression was observed on all cell types detected and the PD-L2 was chiefly on CK-18(+) epithelial cells and CD31(+) endothelial cells. Interestingly, high levels of virus-induced procoagulant molecule fibrinogen-like protein 2 (FGL2) were observed in liver sections from HBV-ACLF, and PD-L1 and PD-L2 expression was also observed on FGL2(+) cells in these patients. Our combined results suggest that the expression of PD-L1 and PD-L2 may be biomarkers to identify and diagnose ACLF, and a clear understanding of their functional roles should further elucidate the pathogenesis of this disease.
Institute of Immunology, PLA, Third Military Medical University, Chongqing, 400038, People's Republic of China.
Dayan
D
Cao
Huan
H
Xu
Guoning
G
Guo
Zhihua
Z
Ruan
Lei
L
Fei
Zhunyi
Z
Xie
Yuzhang
Y
Wu
Yongwen
Y
Chen
D017209:Apoptosis; D060890:B7-H1 Antigen / Q000096:biosynthesis*; D015415:Biomarkers; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D058625:End Stage Liver Disease / Q000378:metabolism / Q000821:virology; D004847:Epithelial Cells / Q000378:metabolism; D005340:Fibrinogen / Q000096:biosynthesis; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism; D008024:Ligands; D008099:Liver / Q000378:metabolism; D017114:Liver Failure, Acute / Q000378:metabolism / Q000821:virology; D008264:Macrophages / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000096:biosynthesis*; D061026:Programmed Cell Death 1 Receptor / Q000096:biosynthesis*; D019562:Viral Load
D060890:B7-H1 Antigen; D015415:Biomarkers; C423236:CD274 protein, human; C095202:FGL2 protein, human; D008024:Ligands; C105992:PDCD1 protein, human; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D005340:Fibrinogen