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




Long-term exposure to Myozyme results in a decrease of anti-drug antibodies in late-onset Pompe disease patients - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

1 Centre de recherche en myologie 2 Institut de Myologie 3 CRC - Centre de Recherche des Cordeliers 4 GENETHON 5 DHUI2B 6 Biochimie métabolique CHU Necker 7 Institut Cochin 8 Service de diabétologie Cochin

Abstract : Immunogenicity of recombinant human acid-alpha glucosidase rhGAA in enzyme replacement therapy ERT is a safety and efficacy concern in the management of late-onset Pompe disease LOPD. However, long-term effects of ERT on humoral and cellular responses to rhGAA are still poorly understood. To better understand the impact of immunogenicity of rhGAA on the efficacy of ERT, clinical data and blood samples from LOPD patients undergoing ERT for >4 years n = 28 or untreated n = 10 were collected and analyzed. In treated LOPD patients, anti-rhGAA antibodies peaked within the first 1000 days of ERT, while long-term exposure to rhGAA resulted in clearance of antibodies with residual production of non-neutralizing IgG. Analysis of  T cell responses to rhGAA showed detectable T cell reactivity only after in vitro restimulation. 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. These results indicate that long-term ERT in LOPD patients results in a decrease in antibody titers and residual production of non-inhibitory IgGs. Immune responses to GAA following long-term ERT do not seem to affect efficacy of ERT and are consistent with an immunomodulatory effect possibly mediated by regulatory T cells.





Autor: Elisa Masat - Pascal Laforêt - Marie De Antonio - Guillaume Corre - Barbara Perniconi - Nadjib Taouagh - Kuberaka Mariampillai -

Fuente: https://hal.archives-ouvertes.fr/



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