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

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.