Effects of costimulation on intrahepatic immunopathogenesis in patients with chronic HBV infection

Inflamm Res. 2014 Mar;63(3):217-29. doi: 10.1007/s00011-013-0691-3. Epub 2013 Dec 14.

Abstract

Objective: Chronic HBV infection can lead to "immune tolerance" in asymptomatic carriers (ACs), "immune injury" in active chronic hepatitis (ACH) patients or "immune abnormality" in cirrhosis (Cir) and hepatocellular carcinoma (HCC) patients. Previous investigations reported that chronic hepatitis presented abnormal expression of costimulatory molecules. We investigated the costimulation profile in the liver of ACs and patients with ACH, Cir and HCC.

Methods: Patients with ACH, Cir and HCC, ACs and normal controls were recruited into the present study. The costimulation profiles and cytokines in the liver of patients were investigated by Western blotting, immunohistochemistry and real-time quantitative PCR. Correlations between serum alanime aminotransferase (ALT) levels, necroinflammation scores, cytokines and costimulatory proteins were assessed.

Results: The ACs presented decreased inflammatory and increased inhibitory costimulation, which was negatively correlated with inflammatory costimulatory proteins and ALT, whereas the ACH patients exhibited increased inflammatory costimulation and decreased inhibitory costimulation, which was correlated with increased ALT. The Cir patients showed both increased inhibitory and inflammatory costimulation. The HCC patients exhibited both decreased inhibitory and inflammatory costimulation.

Conclusion: Costimulation participates in intrahepatic immune responses, and plays important roles in immune tolerance, immune injury and immune abnormalities in patients with chronic HBV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • B7-1 Antigen / metabolism
  • B7-2 Antigen / metabolism
  • Blotting, Western
  • CD28 Antigens / metabolism
  • CD40 Antigens / metabolism
  • CTLA-4 Antigen / metabolism
  • Carcinoma, Hepatocellular / complications
  • Carcinoma, Hepatocellular / immunology
  • Carcinoma, Hepatocellular / pathology
  • Cytokines / biosynthesis
  • Female
  • Hepatitis B, Chronic / immunology*
  • Hepatitis B, Chronic / pathology
  • Humans
  • Immune Tolerance
  • Immunohistochemistry
  • Indicators and Reagents
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-10 / biosynthesis
  • Liver / immunology*
  • Liver / pathology
  • Liver Cirrhosis / immunology
  • Liver Cirrhosis / pathology
  • Liver Function Tests
  • Liver Neoplasms / complications
  • Liver Neoplasms / immunology
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Young Adult

Substances

  • B7-1 Antigen
  • B7-2 Antigen
  • CD28 Antigens
  • CD40 Antigens
  • CTLA-4 Antigen
  • Cytokines
  • Indicators and Reagents
  • RNA, Messenger
  • Intercellular Adhesion Molecule-1
  • Interleukin-10