Telbivudine on IgG-associated hypergammaglobulinemia and TGF-β1 hyperactivity in hepatitis B virus-related liver cirrhosis


Autoři: Cheng-Hsun Ho aff001;  Ting-Tsung Chang aff002;  Rong-Nan Chien aff004
Působiště autorů: Department of Medical Laboratory Science, College of Medicine, I-Shou University, Kaohsiung, Taiwan aff001;  Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan aff002;  Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan aff003;  Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Linkou, Taiwan aff004
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225482

Souhrn

As debate rumbles on about whether anti-hepatitis B virus (HBV) nucleos(t)ide analogue treatments modulate host immune system during end-stage liver diseases, we studied effects of two potent anti-HBV agents, telbivudine or entecavir, on humoral immune activities including cytokine secretion, immunoglobulin production, and IgG-Fc agalactosylation, which is known to induce proinflammatory responses, in liver cirrhosis. Serum IgG-Fc N-glycan structures in patients with HBV-related liver cirrhosis, who had received either telbivudine treatment or entecavir treatment for at least 48 weeks were analyzed using liquid chromatography tandem-mass spectrometry. Levels of cytokines and each immunoglobulin isotype were measured using enzyme-linked immunosorbent assays. Results showed that 48 weeks of entecavir treatment caused HBV DNA loss, alanine aminotransferase normalization, and an amelioration of hypergammaglobulinemia in cirrhotic patients; however, telbivudine treatment, though possessing similar efficacies on HBV suppression and an improvement in liver inflammation to entecavir treatment, did not mitigate IgG-related hypergammaglobulinemia. Levels of IgG and transforming growth factor (TGF)-β1 in sera of the cirrhotic patients before and during treatment were positively correlated. In vitro assays revealed that telbivudine treatment induced TGF-β1 expression in human macrophagic cells. Moreover, recombinant TGF-β1 treatment stimulated cell proliferation and IgG overproduction in human IgG-producing B cell lines. Finally, we found that telbivudine treatment enhanced the proportion of serum IgG-Fc agalactosylation in cirrhotic patients, which was associated with enhanced levels of TGF-β1 and IgG. In conclusion, telbivudine therapy was associated with TGF-β1 hyperactivity, IgG-related hypergammaglobulinemia, and IgG-Fc agalactosylation in HBV-related liver cirrhosis.

Klíčová slova:

Aminotransferases – B cells – Cirrhosis – Cytokines – Hepatitis B virus – Liver diseases – TGF-beta signaling cascade – Hypergammaglobulinemia


Zdroje

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