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Association of PD-L1 gene polymorphisms and circulating sPD-L1 levels with HBV infection susceptibility and related liver disease progression

Xuan Hoan, Nghiem ; Thi Minh Huyen, Pham ; Dinh Tung, Bui ; Phuong Giang, Dao ; Tat Trung, Ngo ; Tien Sy, Bui ; Thi Tuan, Nguyen ; Thi Ngoc Dung, Dang ; Reddy Pallerla, Srinivas ; Velavan, Thirumalaisamy P. ; Hong Bang, Mai ; Huu Song, Le

Gene, 2022-01, Vol.806, p.145935-145935, Article 145935 [Periódico revisado por pares]

Elsevier B.V

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  • Título:
    Association of PD-L1 gene polymorphisms and circulating sPD-L1 levels with HBV infection susceptibility and related liver disease progression
  • Autor: Xuan Hoan, Nghiem ; Thi Minh Huyen, Pham ; Dinh Tung, Bui ; Phuong Giang, Dao ; Tat Trung, Ngo ; Tien Sy, Bui ; Thi Tuan, Nguyen ; Thi Ngoc Dung, Dang ; Reddy Pallerla, Srinivas ; Velavan, Thirumalaisamy P. ; Hong Bang, Mai ; Huu Song, Le
  • Assuntos: Chronic hepatitis B ; Hepatitis B virus ; Hepatocellular carcinoma ; Liver cirrhosis ; PD-1/PD-L1, sPD-L1 ; PD-L1 polymorphism
  • É parte de: Gene, 2022-01, Vol.806, p.145935-145935, Article 145935
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
  • Descrição: •Activation of PD-1/PD-L1 signaling pathway is considered to cause HBV-specific CD8+T cell exhaustion in chronic HBV infection.•Increased expression of PD-L1 involves in various health conditions, including infectious diseases, chronic inflammations, cancers.•The missense variant PD-L1 rs2297136 is associated with HBV infection susceptibility and liver disease progression.•Plasma sPD-L1 correlated with liver inflammation and associated with clinical outcomes in HBV infected patients. Soluble molecules of programmed death ligand 1 (sPD-L1) are known to modulate T-cell depletion, an important mechanism of hepatitis B virus (HBV) persistence and liver disease progression. In addition, PD-L1 polymorphisms in the 3′-UTR can influence PD-L1 expression and have been associated with cancer risk, although not definitively. The purpose of this study was to investigate the association of PD-L1 polymorphisms and circulating levels of sPD-L1 in HBV infection and live disease progression. In this study, five hundred fifty-one HBV infected patients of the three clinically well-defined subgroups chronic hepatitis B (CHB, n = 186), liver cirrhosis (LC, n = 142) and hepatocellular carcinoma (HCC, n = 223) and 240 healthy individuals (HC) were enrolled. PD-L1 polymorphisms (rs2297136 and rs4143815) were genotyped by in-house validated ARMS assays. Logistic regression models were applied in order to determine the association of PD-L1 polymorphisms with HBV infection as well as with progression of related liver diseases. Plasma sPD-L1 levels were quantified by ELISA assays. The PD-L1 rs2297136 AA genotype was associated with HBV infection susceptibility (HBV vs. HC: OR = 1.6; 95%CI = 1.1–2.3; p = 0.0087) and disease progression (LC vs. CHB: OR = 1.8; 95%CI = 1.1–2.9; p = 0.018). Whereas, the rs2297136 GG genotype was a protective factor for HCC development. Plasma sPD-L1 levels were significantly high in HBV patients (p < 0.0001) and higher in the LC followed by CHB and HCC groups. High sPD-L1 levels correlated with increased liver enzymes and with advanced liver disease progression (Child-pugh C > B > A, p < 0.0001) and BCLC classification (BCLC D > C > B > A, p = 0.031). We could, for the first time, conclude that PD-L1 rs2297136 polymorphism and plasma sPD-L1 protein levels associate with HBV infection and HBV-related liver disease progression.
  • Editor: Elsevier B.V
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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