Increased levels of soluble HLA-G molecules in Tunisian patients with chronic hepatitis B infection

J Viral Hepat. 2017 Nov;24(11):1016-1022. doi: 10.1111/jvh.12718. Epub 2017 Jun 10.

Abstract

Hepatitis B virus (HBV) infection is a global health problem. The mechanisms of immune tolerance in HBV infection are still unclear. The host immune response plays a critical role in determining the outcome of HBV infection. Human leucocyte antigen-G (HLA-G) is involved in immunotolerogenic process and infectious diseases. This study aimed to explore the implication of soluble HLA-G (sHLA-G) and its isoforms in HBV infection. Total sHLA-G (including shedding HLA-G1 and HLA-G5) was analysed by ELISA in 95 chronic HBV patients, 83 spontaneously resolvers and 100 healthy controls (HC). To explore the presence of sHLA-G dimers, we performed an immunoprecipitation and a Western blot analysis on positive samples for sHLA-G in ELISA. The serum levels of sHLA-G were significantly increased in patients with chronic HBV patients compared to spontaneously resolvers and HC (P<.0001). Interestingly, we found an increased level of sHLA-G1 in chronic HBV patients than in spontaneously resolvers and HC (P<.001). In addition, the expression of HLA-G5 seems to be higher in the sera of chronic HBV patients than spontaneously resolvers (P=.026). The analysis of HLA-G dimers showed the presence of homodimers in 93% of chronic HBV patients, 67% in spontaneously resolvers and 60% in HC. These results provide evidence that sHLA-G may have a crucial role in the outcome of HBV infection and could be proposed as a biomarker for infection outcome. Based on its tolerogenic function, HLA-G might be considered as a new promising immunotherapeutic approach to treat the chronic infection with HBV.

Keywords: hepatitis B virus clearance; hepatitis B virus infection; human leucocyte antigen-G isoforms; soluble human leucocyte antigen-G.

MeSH terms

  • Adult
  • Biomarkers
  • Blotting, Western
  • Female
  • HLA-G Antigens / blood*
  • HLA-G Antigens / chemistry
  • HLA-G Antigens / immunology*
  • Hepatitis B virus / immunology
  • Hepatitis B, Chronic / blood*
  • Hepatitis B, Chronic / epidemiology*
  • Hepatitis B, Chronic / virology
  • Humans
  • Liver Function Tests
  • Male
  • Population Surveillance
  • Protein Multimerization
  • Tunisia / epidemiology
  • Young Adult

Substances

  • Biomarkers
  • HLA-G Antigens