Laaribi A B, Bortolotti D, Hannachi N, Mehri A, Hazgui O, Ben Yahia H, Babay W, Belhadj M, Chaouech H, Yacoub S, Letaief A, Ouzari H I, Boudabous A, Di Luca D, Boukadida J, Rizzo R, Zidi I
Laboratory of Microorganisms and Actives Biomolecules, Sciences Faculty of Tunis, University of Tunis El Manar, Tunis, Tunisia.
Laboratory of Microbiology and Immunology, UR12SP34, University Hospital Farhat Hached, Sousse, Tunisia.
J Viral Hepat. 2017 Nov;24(11):1016-1022. doi: 10.1111/jvh.12718. Epub 2017 Jun 10.
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.
乙型肝炎病毒（HBV）感染是一个全球性的健康问题。HBV感染中免疫耐受的机制仍不清楚。宿主免疫反应在决定HBV感染的结果中起着关键作用。人类白细胞抗原-G（HLA-G）参与免疫耐受过程和传染病。本研究旨在探讨可溶性HLA-G（sHLA-G）及其异构体在HBV感染中的意义。采用酶联免疫吸附测定（ELISA）分析了95例慢性HBV患者、83例自然康复者和100例健康对照者（HC）的总sHLA-G（包括可溶性HLA-G1和HLA-G5）。为了探究sHLA-G二聚体的存在情况，我们对ELISA中sHLA-G呈阳性的样本进行了免疫沉淀和蛋白质印迹分析。与自然康复者和HC相比，慢性HBV患者的血清sHLA-G水平显著升高（P<0.0001）。有趣的是，我们发现慢性HBV患者的sHLA-G1水平高于自然康复者和HC（P<0.001）。此外，慢性HBV患者血清中HLA-G5的表达似乎高于自然康复者（P=0.026）。HLA-G二聚体分析显示，93%的慢性HBV患者、67%的自然康复者和60%的HC存在同源二聚体。这些结果提供了证据，表明sHLA-G可能在HBV感染的结果中起关键作用，并可被提议作为感染结果的生物标志物。基于其免疫耐受功能，HLA-G可能被认为是一种治疗慢性HBV感染的有前景的新免疫治疗方法。
