Long-term exposure to Myozyme results in a decrease of anti-drug antibodies in late-onset Pompe disease patients.
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.
University Pierre and Marie Curie, INSERM, UMR974, Paris, France.
Elisa
E
Masat
University Pierre and Marie Curie, INSERM, UMR974, Paris, France.|Paris-Est neuromuscular center, Institute of Myology, Pitié-Salpêtrière Hospital, AP-HP, Paris, France.
Pascal
P
Laforêt
University Paris Descartes, INSERM, UMR1138, Paris, France.
Marie
M
De Antonio
Genethon, INSERM, UMR951, Evry, France.
Guillaume
G
Corre
Paris-Est neuromuscular center, Institute of Myology, Pitié-Salpêtrière Hospital, AP-HP, Paris, France.
Barbara
B
Perniconi
Paris-Est neuromuscular center, Institute of Myology, Pitié-Salpêtrière Hospital, AP-HP, Paris, France.
Nadjib
N
Taouagh
Department of Internal Medicine and Clinical Immunology, DHUI2B, Pitié-Salpêtrière Hospital, AP-HP, Paris, France.
Kuberaka
K
Mariampillai
University Pierre and Marie Curie, INSERM, UMR974, Paris, France.
Damien
D
Amelin
University Pierre and Marie Curie, INSERM, UMR974, Paris, France.
Wladimir
W
Mauhin
Neuromuscular Physiology and Evaluation Lab, Institute of Myology, Paris, France.
Jean-Yves
JY
Hogrel
Department of Metabolic Biochemistry, Necker Hospital, Paris, France.
Catherine
C
Caillaud
Genethon, INSERM, UMR951, Evry, France.
Giuseppe
G
Ronzitti
Genethon, INSERM, UMR951, Evry, France.
Francesco
F
Puzzo
University Pierre and Marie Curie, INSERM, UMR974, Paris, France.
Klaudia
K
Kuranda
Genethon, INSERM, UMR951, Evry, France.
Pasqualina
P
Colella
Institute Cochin, INSERM U1016, CNRS UMR8104, Paris, France.|University Paris Descartes, Faculty of Medicine, Paris, France.|Department of diabetology, Cochin Hospital, AP-HP, Paris, France.
Roberto
R
Mallone
University Pierre and Marie Curie, INSERM, UMR974, Paris, France.|Department of Internal Medicine and Clinical Immunology, DHUI2B, Pitié-Salpêtrière Hospital, AP-HP, Paris, France.
Olivier
O
Benveniste
University Pierre and Marie Curie, INSERM, UMR974, Paris, France.|Genethon, INSERM, UMR951, Evry, France.
Federico
F
Mingozzi
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000906:Antibodies / Q000097:blood*; D016022:Case-Control Studies; D003713:Dendritic Cells / Q000276:immunology; D056947:Enzyme Replacement Therapy / Q000009:adverse effects* / Q000379:methods; D005260:Female; D006009:Glycogen Storage Disease Type II / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome; D000520:alpha-Glucosidases / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*
D000906:Antibodies; C508594:IL2 protein, human; D007074:Immunoglobulin G; D007376:Interleukin-2; C509951:GAA protein, human; D000520:alpha-Glucosidases