Long-term exposure to Myozyme results in a decrease of anti-drug antibodies in late-onset Pompe disease patients

Area of Science:

• Immunology
• Biochemistry
• Genetics

Background:

• Immunogenicity of recombinant human acid-alpha glucosidase (rhGAA) is a key concern in enzyme replacement therapy (ERT) for late-onset Pompe disease (LOPD).
• Long-term humoral and cellular immune responses to rhGAA in LOPD patients undergoing ERT remain incompletely understood.
• Understanding these immune responses is crucial for assessing ERT safety and efficacy in LOPD management.

Purpose of the Study:

• To investigate the long-term immunogenicity of rhGAA in LOPD patients receiving ERT.
• To analyze the impact of sustained ERT on both antibody and T cell responses to rhGAA.
• To correlate immune responses with ERT efficacy in LOPD.

Main Methods:

• Clinical data and blood samples were collected from LOPD patients with >4 years of ERT (n=28) and untreated controls (n=10).
• Humoral responses were assessed by measuring anti-rhGAA antibody titers and IgG subclasses.
• Cellular responses were evaluated through T cell reactivity assays and cytokine/chemokine profiling following in vitro restimulation.

Main Results:

• Anti-rhGAA antibody titers peaked within the first 1000 days of ERT, followed by antibody clearance and residual production of non-neutralizing IgG in long-term treated patients.
• Detectable T cell reactivity to rhGAA was observed only after in vitro restimulation.
• Upregulation of cytokines and chemokines was noted in both treated and untreated LOPD subjects, with IL-2 secretion specific to ERT recipients.

Conclusions:

• Long-term ERT in LOPD patients leads to reduced antibody titers and the persistence of non-inhibitory IgGs.
• Immune responses to rhGAA during extended ERT do not seem to compromise treatment efficacy.
• These findings suggest a potential immunomodulatory effect of ERT, possibly involving regulatory T cells.