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

Miklos Banati, Zsolt Hosszu, Anita Trauninger, L. Szereday, Zsolt Illes

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)720-726
Number of pages7
JournalMuscle and Nerve
Volume44
Issue number5
DOIs
Publication statusPublished - Nov 2011

Fingerprint

Glycogen Storage Disease Type II
Enzyme Replacement Therapy
T-Lymphocytes
Interferon-gamma
Perforin
Interleukin-17
Rare Diseases
Interleukin-4
Antibody Formation
Late Onset Disorders
Anti-Idiotypic Antibodies
Interleukin-6
Tumor Necrosis Factor-alpha
human GAA protein

Keywords

  • A-glucosidase
  • Enzyme replacement therapy
  • Inherited muscle diseases
  • Late-onset glycogenosis ii
  • Myozyme
  • Pompe disease
  • T-cell response

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Physiology (medical)
  • Physiology

Cite this

Enzyme replacement therapy induces T-cell responses in late-onset Pompe disease. / Banati, Miklos; Hosszu, Zsolt; Trauninger, Anita; Szereday, L.; Illes, Zsolt.

In: Muscle and Nerve, Vol. 44, No. 5, 11.2011, p. 720-726.

Research output: Contribution to journalArticle

Banati, Miklos ; Hosszu, Zsolt ; Trauninger, Anita ; Szereday, L. ; Illes, Zsolt. / Enzyme replacement therapy induces T-cell responses in late-onset Pompe disease. In: Muscle and Nerve. 2011 ; Vol. 44, No. 5. pp. 720-726.
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