title: Enzyme replacement therapy induces T-cell responses in late-onset Pompe disease.
abstract: BACKGROUND
  Enzyme replacement therapy (ERT) in ultra-orphan Pompe disease generates anti-rhGAA antibodies, which may interfere with efficacy.
  
  
  METHODS
  rhGAA-specific T-cell responses were examined at different time-points in 6 Hungarian patients treated with rhGAA and compared with 1 untreated patient and 5 healthy controls.
  
  
  RESULTS
  The ex vivo percentage of activated T cells was increased in treated patients. rhGAA stimulation in vitro generated a dose-dependent increase in intracellular interferon-gamma (IFN-γ) expression in CD4(+) and CD8(+) T cells. Isolated CD4(+) and CD8(+) T cells produced increased amounts of IFN-γ and tumor necrosis factor-alpha (TNF-α) in half of the patients after in vitro stimulation with rhGAA, whereas interleukin (IL)-4, IL-6, and IL-17 levels were not elevated. Expression of cytotoxic FasL and perforin molecules by natural killer (NK), NKT-like, and CD8(+) T cells were not increased ex vivo.
  
  
  CONCLUSIONS
  We found that enzyme replacement therapy (ERT) induces pro-inflammatory T-cell responses in addition to the antibody response in Pompe disease.
authors.affiliation: Department of Neurology, Ret u.2, University of Pécs, Pécs 7623, Hungary.
authors.forename: Miklos
authors.initials: M
authors.lastname: Banati
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Hosszu
authors.forename: Anita
authors.initials: A
authors.lastname: Trauninger
authors.forename: Laszlo
authors.initials: L
authors.lastname: Szereday
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Illes
mesh_terms: D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D002478:Cells, Cultured; D056947:Enzyme Replacement Therapy / Q000379:methods*; D005260:Female; D006009:Glycogen Storage Disease Type II / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D000520:alpha-Glucosidases / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: C509951:GAA protein, human; D000520:alpha-Glucosidases