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In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Upregulation of several cytokines and chemokines was detectable in both treated and untreated LOPD subjects, while IL2 secretion was detectable only in subjects who received ERT.
The infantile form of PD is the most severe and, if not treated, is associated with early lethality 3 , 4. The adult form of the disease, known as late onset Pompe disease LOPD , is compatible with life, although it is associated with progressive deterioration of skeletal muscle function, leading in some cases to significant disability and need for assisted ventilation 5 , 6. The approval of recombinant human GAA rhGAA Myozyme for the treatment of Pompe disease resulted in a significant improvement of both life expectancy and quality of life of infantile PD patients 7 , although long-term follow up of children treated with enzyme replacement therapy ERT revealed occurrence of symptoms resulting from the incomplete correction of the enzyme deficiency in certain tissues 8.
One important common side effect of ERT for Pompe disease is the induction of antibody responses against the infused protein, a phenomenon particularly frequent in infantile patients who are cross-reactive immunological material CRIM -negative 4 , 12 , that is associated with lack of efficacy and poor prognosis 13 , In addition to neutralizing antibody responses, life-threatening allergic reactions associated with the production of immunoglobulin Ig E specific to the enzyme have been reported to occur following the infusion of rhGAA Moreover, mechanistic insights into the immunogenicity of rhGAA are lacking.
In this study we demonstrate that rhGAA infusion results in the early production of high-titer antibodies in a subset of subjects, however antibodies appear to drop over time with continuation of ERT. IgG subclass characterization shows production of non-inhibitory antibodies with no evident effect on enzyme activity or uptake, while rhGAA-specific T cell activation profile is consistent with immune modulation, possibly mediated by regulatory T cells.
