title: Adaptive immune responses during acute uncomplicated and fulminant hepatitis E.
abstract: OBJECTIVE
  Hepatitis E virus (HEV) infection is endemic in several developing countries. Clinical manifestations of this infection vary widely from asymptomatic infection to uncomplicated acute viral hepatitis and fulminant hepatic failure. The pathogenesis of this disease and the reason of varying disease severity remain unknown. In viral infections, tissue injury can be caused either by virus itself or by host immune responses directed against infected cells. We therefore studied adaptive immune responses to HEV antigens in patients with hepatitis E of varying disease severity and healthy controls.
  
  
  METHODS
  Cytokine secreting CD4+ T cells and antibody-producing B cells specific for HEV were enumerated through intracellular cytokine staining and enzyme-linked immunosorbent spot assay, respectively.
  
  
  RESULTS
  Patients with fulminant hepatitis E had a less marked expansion of HEV-specific interferon-γ or tumor necrosis factor-a secreting CD4+ T cells than patients with uncomplicated hepatitis E and healthy controls. These patients also had fewer CD4+ T cells that produce γ-interferon or tumor necrosis factor-a upon in vitro polyclonal stimulation. In addition, patients with fulminant disease had a more marked expansion of B cells that can secrete immunoglobulin G anti-HEV than patients with uncomplicated infection and control patients.
  
  
  CONCLUSIONS
  These findings suggest that less-marked antiviral cellular immune responses and heightened antiviral humoral responses are associated with a more severe disease during HEV infection.
authors.affiliation: Department of Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Ratika
authors.initials: R
authors.lastname: Srivastava
authors.forename: Rakesh
authors.initials: R
authors.lastname: Aggarwal
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Sachdeva
authors.forename: Mohammad Intakhab
authors.initials: MI
authors.lastname: Alam
authors.forename: Shahid
authors.initials: S
authors.lastname: Jameel
authors.forename: Sita
authors.initials: S
authors.lastname: Naik
mesh_terms: D000208:Acute Disease; D056704:Adaptive Immunity / Q000187:drug effects; D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006508:Hepatitis Antibodies / Q000378:metabolism; D016751:Hepatitis E / Q000276:immunology*; D016752:Hepatitis E virus / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000378:metabolism; D012720:Severity of Illness Index; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism; D055815:Young Adult
chemical_list: D006508:Hepatitis Antibodies; D007074:Immunoglobulin G; C400971:ORF2 protein, Hepatitis E virus; C400973:ORF3 protein, Hepatitis E virus; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; D015759:Ionomycin; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate