Soluble human leukocyte antigen‐G expression in hepatitis B virus infection and hepatocellular carcinoma

Park, Yongjung; Lim, Hwan Sub; Kim, Y. S.; Hong, Duck Jin; Kim, H. S.

doi:10.1111/j.1399-0039.2011.01814.x

Cited by 33 publications

(28 citation statements)

References 29 publications

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“…7 Soluble HLA-G isoforms can form homodimers (78-kDa) through the generation of Cys42-Cys42 disulfide bond. 8 Several reports were interested into the study of HLA-G implication in the pathogenesis of HBV infection, [9][10][11] whereas other studies focused only on the total sHLA-G levels and its correlation to clinical outcomes of HBV infection. In this study, we evaluated sHLA-G serum levels as well as its dimerization in patients with chronic HBV infections, spontaneous resolvers and healthy controls (HC).…”

Section: Discussionmentioning

confidence: 99%

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

Laaribi

Bortolotti

Hannachi

et al. 2017

Journal of Viral Hepatitis

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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.

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Section: Discussionmentioning

confidence: 99%

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

Laaribi

Bortolotti

Hannachi

et al. 2017

Journal of Viral Hepatitis

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“…Park et al detected higher levels of sHLA-G in patients with active HBV and HCC than healthy controls. Their results also showed increased levels of sHLA-G in early stages of HBV-mediated HCC [89]. However, in a recent study, we observed no correlation between HLA-G expression and the presence of HBV genome in HCC tissues [48].…”

Section: (41)mentioning

confidence: 64%

HLA-G: Facts and Fictions

Shahraki

Alavianmehr

Farjadian

2018

Asian Pac J Cancer Biol

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Human leukocyte antigen (HLA)-G is a nonclassical MHC class I molecule with modulatory effects on NK and T cells. Unlike classical HLA class I molecules, HLA-G has seven isoforms, three of which are soluble. Soluble HLA-G molecules are reportedly able to transduce negative signals to immune cells after interacting with their corresponding receptors. The expression of these molecules plays significant roles in maternal tolerance against semi-allogenic fetuses. Overexpression of HLA-G in tumors and increased serum levels of soluble HLA-G have been reported in different malignancies, and these changes may be involved in tumoral immune evasion and cancer progression. To improve immune responses against tumor cells, the downmodulation of HLA-G by siRNA or blocking monoclonal antibodies can be helpful in cancer immunotherapy. Additionally, HLA-G can be considered a potential biomarker for the diagnosis and/or prognosis of certain cancers. Although polymorphism of the HLA-G gene-coding region is more limited than in classical HLA class I, some genetic variations in regulatory regions of the gene control the expression level of this molecule. Furthermore, epigenetic factors such as infections may affect the expression of HLA-G in infection-related cancers.

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“…Moreover, the concentrations of sHLA‐G were higher in the patients with HCC than in those with liver cirrhosis or active hepatitis B, suggesting that serum sHLA‐G concentrations may be associated with the different phases of hepatitis B infection. They did not find any association between sHLA‐G concentrations and HCC stage, number of tumors, pathologic grade and presence of vascular invasion . Other study, examining 15 SNPs in the nonclassical class I alleles, found that the SNPs rs17875380, rs41557518, rs114465251, and rs115492845 were associated with susceptibility to chronic hepatitis B infection or HCC, and HLA‐F*01:04 , HLA‐G*01:05N , and HLA‐E*01:01 were associated with hepatitis B or hepatitis B with HCC, concluding that these polymorphisms may play an important role in immune surveillance of hepatitis B and HCC, possibly leading to immune responses to virus or cancer cells .…”

Section: Discussionmentioning

confidence: 96%

The 14bp‐deletion allele in the HLA‐G gene confers susceptibility to the development of hepatocellular carcinoma in the Brazilian population

et al. 2013

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Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class I molecule involved in tumor escape mechanisms. Considering that the HLA-G 14bp insertion/deletion polymorphism is located at the 3' untranslated region (3'UTR) in exon 8, and since it has been associated with the magnitude of HLA-G production, we studied the association of 14bp insertion/deletion polymorphism with the risk of developing hepatocellular carcinoma (HCC). A total of 109 HCC patients followed at the University Hospital, Faculty of Medicine of Ribeirão Preto, São Paulo, Brazil, and 202 healthy controls from the same geographic area were genotyped for the 14bp insertion/deletion polymorphism using polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis. Compared to controls, the frequency of the 14bp deletion allele was overrepresented in HCC patients (65% versus 56%, respectively, P = 0.0326). The 14bp deletion conferred an odds ratio (OR) of 1.46 [95% confidence interval (CI): 1.04-2.05]. Similarly, the deletion/deletion genotype was marginally overrepresented in HCC patients (45% versus 35% in controls, P = 0.0871), conferring an OR of 1.54 (95% CI: 0.96-2.48). The frequencies of the deletion/insertion or insertion/insertion genotypes observed in patients were not statistically different from those observed in controls (P > 0.05). Our results suggest that the 14bp-deletion allele in HLA-G gene is associated with HCC susceptibility in a Brazilian population.

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Soluble human leukocyte antigen‐G expression in hepatitis B virus infection and hepatocellular carcinoma

Cited by 33 publications

References 29 publications

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

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

HLA-G: Facts and Fictions

The 14bp‐deletion allele in the HLA‐G gene confers susceptibility to the development of hepatocellular carcinoma in the Brazilian population

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