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

Scientific Reports2016Vol. 6(1), pp. 36182–36182

Citations Over TimeTop 11% of 2016 papers

Elisa Masat, Pascal Laforêt, Marie De Antonio, Guillaume Corre, Barbara Perniconi, Nadjib Taouagh, K. Mariampillai, Damien Amelin, Wladimir Mauhin, Jean‐Yves Hogrel, Catherine Caillaud, Giuseppe Ronzitti, Francesco Puzzo, Klaudia Kuranda, Pasqualina Colella, Roberto Mallone, Olivier Benvéniste, Federico Mingozzi, French Pompe Registry Study Group, Guillaume Bassez, A.-L. Bédat-Millet, Anthony Béhin, B. Eymard, Sarah Léonard-Louis, T. Stojkovic, A. Canal, V. Decostre, Françoise Bouhour, F. Boyer, Y. Castaing, Françoise Chapon, Pascal Cintas, I. Durieu, Andoni Echaniz‐Laguna, Léonard Feasson, A. Furby, Dalil Hamroun, Xavier Ferrer, Guilhem Solé, Roseline Froissart, Monique Piraud, Dominique P. Germain, Karelle Bénistan, N. Guffon-Fouilhoux, Hubert Journel, Pierre Labauge, A. Lacour, Antonin Lévy, Armelle Magot, Yann Péréon, Marie-Christine Minot-Myhié, Aleksandra Nadaj‐Pakleza, C. Nathier, David Orlikowski, N. Pellegrini, P. Petiot, Julien Praline, Frédéric Lofaso, Hélène Prigent, A. Dutry, Dimitri Renard, Sabrina Sacconi, Claude Desnuelle, Emmanuelle Salort‐Campana, Jean Pouget, V. Tiffreau, Didier Vincent, Fabien Zagnoli

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.

Citations Over TimeTop 11% of 2016 papers

Abstract

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