Enzyme replacement therapy induces T‐cell responses in late‐onset Pompe disease

INTRODUCTION: 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.