The characteristic expression of B7-H3 and B7-H4 in liver biopsies from patients with HBV-related acute-on-chronic liver failure

Pathol Int. 2012 Oct;62(10):665-74. doi: 10.1111/j.1440-1827.2012.02856.x.

Abstract

Hepatitis B virus (HBV) 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 effective treatments. B7-H3 and B7-H4 are two novel members of the B7 superfamily that are actively involved in regulating the pathogenesis of infectious diseases. However, the intrahepatic expression of both members in HBV-ACLF patients has yet to be described. In this study, we analyzed the expression of B7-H3 and B7-H4 in HBV-ACLF biopsies by immunohistochemistry. Our results showed that both members were observed in all HBV-ACLF samples, and their expression was chiefly observed on infiltrating inflammatory cells and the damaged bile ducts. Immunofluorescence double staining showed that B7-H4 was expressed chiefly on CD3(+) T cells, CD68(+) macrophages, CK-18(+) bile ducts, and CD31(+) endothelial cells, while B7-H3 was found on all cell types detected. The expression of the programmed death (PD)-1 ligands, PD-L1 and PD-L2, was also detected in these liver tissues and they were found to be co-expressed with B7-H3 and B7-H4. These results suggest that the B7-family signaling is most likely to affect the pathogenesis of this disease, and a clear understanding of their functional roles may further elucidate the disease process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • B7 Antigens / metabolism*
  • B7-H1 Antigen / metabolism
  • Bile Ducts
  • Biomarkers / metabolism
  • Biopsy
  • Disease Progression
  • End Stage Liver Disease / immunology
  • End Stage Liver Disease / metabolism*
  • End Stage Liver Disease / virology
  • Hepatitis B virus / pathogenicity*
  • Hepatitis B, Chronic / immunology
  • Hepatitis B, Chronic / metabolism*
  • Hepatitis B, Chronic / virology
  • Humans
  • Immunohistochemistry
  • Liver / metabolism
  • Liver Failure, Acute / immunology
  • Liver Failure, Acute / metabolism*
  • Liver Failure, Acute / virology
  • Macrophages / immunology
  • Male
  • Middle Aged
  • Phenotype
  • Prognosis
  • Programmed Cell Death 1 Ligand 2 Protein / metabolism
  • T-Lymphocytes / immunology
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1 / metabolism*

Substances

  • B7 Antigens
  • B7-H1 Antigen
  • Biomarkers
  • CD274 protein, human
  • CD276 protein, human
  • PDCD1LG2 protein, human
  • Programmed Cell Death 1 Ligand 2 Protein
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1
  • VTCN1 protein, human