title: Pegylated Interferon α-2a Triggers NK-Cell Functionality and Specific T-Cell Responses in Patients with Chronic HBV Infection without HBsAg Seroconversion.
abstract: Pegylated interferon α-2a (Peg-IFN-α) represents a therapeutic alternative to the prolonged use of nucleos(t)ide analog (NA) in chronic hepatitis B (CHB) infection. The mechanisms leading to a positive clinical outcome remain unclear. As immune responses are critical for virus control, we investigated the effects of Peg-IFN-α on both innate and adaptive immunity, and related it to the clinical evolution. The phenotypic and functional features of the dendritic cells (DCs), natural killer (NK) cells and HBV-specific CD4/CD8 T cells were analyzed in HBeAg-negative CHB patients treated for 48-weeks with NA alone or together with Peg-IFN-α, before, during and up to 2-years after therapy. Peg-IFN-α induced an early activation of DCs, a potent expansion of the CD56bright NK subset, and enhanced the activation and functionality of the CD56dim NK subset. Peg-IFN-α triggered an increase in the frequencies of Th1- and Th17-oriented HBV-specific CD4/CD8 T cells. Peg-IFN-α reversed the unresponsiveness of patients to a specific stimulation. Most of the parameters returned to baseline after the stop of Peg-IFN-α therapy. Peg-IFN-α impacts both innate and adaptive immunity, overcoming dysfunctional immune responses in CHB patients. These modulations were not associated with seroconversion, which questioned the benefit of the add-on Peg-IFN-α treatment.
authors.affiliation: University Grenoble Alpes, Grenoble, F-38041 France; INSERM, U1209, Immunobiology and Immunotherapy of Chronic Deseases, La Tronche, F-38706 France.|CHU Grenoble, Michallon Hospital, Hepato-gastroenterology unit, Grenoble, F-38043 France.
authors.forename: Juliana
authors.initials: J
authors.lastname: Bruder Costa
authors.affiliation: CHU Grenoble, Michallon Hospital, Hepato-gastroenterology unit, Grenoble, F-38043 France.|University Grenoble Alpes, Grenoble, F-38041 France; INSERM, U1209, Analytic Immunology of chronic pathologies, La Tronche, F-38706 France.
authors.forename: Tania
authors.initials: T
authors.lastname: Dufeu-Duchesne
authors.affiliation: CHU Grenoble, Michallon Hospital, Hepato-gastroenterology unit, Grenoble, F-38043 France.|University Grenoble Alpes, Grenoble, F-38041 France; INSERM, U1209, Analytic Immunology of chronic pathologies, La Tronche, F-38706 France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Leroy
authors.affiliation: ANRS (France REcherche Nord & sud Sida-hiv Hépatites: FRENSH), Paris, France.
authors.forename: Inga
authors.initials: I
authors.lastname: Bertucci
authors.affiliation: Department of Virology, Henri Mondor Hospital, University Paris-Est and Inserm U955, Creteil, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Bouvier-Alias
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), 75012, Paris, France.
authors.forename: Noelle
authors.initials: N
authors.lastname: Pouget
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), 75012, Paris, France.
authors.forename: Ophelie
authors.initials: O
authors.lastname: Brevot-Lutton
authors.affiliation: Hepato-gastroenterology department Hospital Saint Joseph, Marseille, 13008 France.
authors.forename: Marc
authors.initials: M
authors.lastname: Bourliere
authors.affiliation: INSERM U1052-CNRS 5286, Cancer Research Center of Lyon (CRCL), Lyon, France.|Hepatology Department, Hospices Civils de Lyon, Lyon, France.|Université de Lyon, Lyon, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Zoulim
authors.affiliation: University Grenoble Alpes, Grenoble, F-38041 France; INSERM, U1209, Immunobiology and Immunotherapy of Chronic Deseases, La Tronche, F-38706 France.|EFS Rhone-Alpes, R&D Laboratory, La Tronche, F-38701 France.
authors.forename: Joel
authors.initials: J
authors.lastname: Plumas
authors.affiliation: University Grenoble Alpes, Grenoble, F-38041 France; INSERM, U1209, Immunobiology and Immunotherapy of Chronic Deseases, La Tronche, F-38706 France.|EFS Rhone-Alpes, R&D Laboratory, La Tronche, F-38701 France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Aspord
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D004279:DNA, Viral; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology* / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D008111:Liver Function Tests; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011092:Polyethylene Glycols / Q000494:pharmacology* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D015415:Biomarkers; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a