title: Association of serum IgG N-glycome and transforming growth factor-β1 with hepatitis B virus e antigen seroconversion during entecavir therapy.
abstract: Aberrant serum IgG N-glycome has been demonstrated in various autoimmune diseases and viral infections. However, the correlation between serum IgG N-glycome and cytokine is unclear. In addition, the clinical relevance of IgG glycosylation and cytokine changes in the treatment outcome of chronic hepatitis B (CHB) has never been assessed. One hundred and three treatment-naive patients with CHB and 101 healthy controls were enrolled in this retrospective cohort study. Serum samples in patients before and after 48weeks of entecavir treatment were collected. In-gel trypsinized serum IgG heavy chain was analyzed using liquid chromatography-tandem mass spectrometry. Selected ion chromatograms corresponding to 10 N-glycoforms on asparagine 297 were individually extracted to calculate the percentage of each glycoforms. Serum cytokine profiles were examined using enzyme-linked immunosorbent assay. Forty-eight weeks of entecavir treatment resulted in decreases in galactose-deficient (total G0) IgG and transforming growth factor (TGF)-β1 levels (both P<0.001) in patients with CHB. The changes in TGF-β1 (ΔTGF-β1) and IgG total G0 (Δtotal G0) levels during treatment were significantly correlated (r=0.403, P<0.001). Furthermore, higher levels of Δtotal G0 (P<0.01) and ΔTGF-β1 (P<0.001) were found in hepatitis B virus e antigen (HBeAg)-positive patients than in HBeAg-negative patients and were also found in patients with HBeAg seroconversion at week 48. The area under the receiver operating characteristic (ROC) curves for Δtotal G0 and ΔTGF-β1 to discriminate a week-48 HBeAg seroconversion were 0.835 and 0.830, respectively. These results suggested a correlation between serum cytokine and IgG N-glycome and its effect on the outcome of entecavir treatment in patients with CHB.
authors.affiliation: Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; Infectious Disease and Signaling Research Center, National Cheng Kung University, Tainan, Taiwan. Electronic address: chenghsunho@gmail.com.
authors.forename: Cheng-Hsun
authors.initials: CH
authors.lastname: Ho
authors.affiliation: Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung, Taiwan. Electronic address: ronald@adm.cgmh.org.tw.
authors.forename: Rong-Nan
authors.initials: RN
authors.lastname: Chien
authors.affiliation: Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan. Electronic address: pncheng@mail.ncku.edu.tw.
authors.forename: Pin-Nan
authors.initials: PN
authors.lastname: Cheng
authors.affiliation: Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung, Taiwan. Electronic address: coolsean0912@gmail.com.
authors.forename: Cheng-Kun
authors.initials: CK
authors.lastname: Liu
authors.affiliation: Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung, Taiwan. Electronic address: roro89121@hotmail.com.
authors.forename: Chih-Sheng
authors.initials: CS
authors.lastname: Su
authors.affiliation: Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan. Electronic address: wichin@mail.ncku.edu.tw.
authors.forename: I-Chin
authors.initials: IC
authors.lastname: Wu
authors.affiliation: Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; Infectious Disease and Signaling Research Center, National Cheng Kung University, Tainan, Taiwan. Electronic address: graceliu8911@gmail.com.
authors.forename: Wen-Chun
authors.initials: WC
authors.lastname: Liu
authors.affiliation: Department of Chemistry, National Cheng Kung University, Tainan, Taiwan. Electronic address: shchen@mail.ncku.edu.tw.
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; Infectious Disease and Signaling Research Center, National Cheng Kung University, Tainan, Taiwan; Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan. Electronic address: ttchang@mail.ncku.edu.tw.
authors.forename: Ting-Tsung
authors.initials: TT
authors.lastname: Chang
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D006031:Glycosylation; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000097:blood / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000378:metabolism* / Q000821:virology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D053773:Transforming Growth Factor beta1 / Q000097:blood*
chemical_list: D000914:Antibodies, Viral; D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; C413685:entecavir; D006147:Guanine
keywords: Chronic hepatitis B; Entecavir; Glycosylation; IgG; TGF-β1