Deep characterization of the anti-drug ...
Type de document :
Article dans une revue scientifique
PMID :
URL permanente :
Titre :
Deep characterization of the anti-drug antibodies developed in Fabry disease patients, a prospective analysis from the French multicenter cohort FFABRY
Auteur(s) :
Mauhin, Wladimir [Auteur]
Centre de recherche en Myologie – U974 SU-INSERM
Lidove, Olivier [Auteur]
Centre de recherche en Myologie – U974 SU-INSERM
Amelin, Damien [Auteur]
Centre de recherche en Myologie – U974 SU-INSERM
Lamari, Foudil [Auteur]
Université Pierre et Marie Curie - Paris 6 [UPMC]
Caillaud, Catherine [Auteur]
Institut Necker Enfants-Malades [INEM - UM 111 (UMR 8253 / U1151)]
Mingozzi, Federico [Auteur]
Centre de recherche en Myologie – U974 SU-INSERM
Dzangue-Tchoupou, Gaelle [Auteur]
Centre de recherche en Myologie – U974 SU-INSERM
Arouche-Delaperche, Louiza [Auteur]
Centre de recherche en Myologie – U974 SU-INSERM
Douillard, Claire [Auteur]
Dussol, Bertrand [Auteur]
Aix Marseille Université [AMU]
Leguy-Seguin, Vanessa [Auteur]
D''halluin, Pauline [Auteur]
Université Francois Rabelais [Tours]
Noel, Esther [Auteur]
Zenone, Thierry [Auteur]
Matignon, Marie [Auteur]
Université Paris-Est Créteil Val-de-Marne - Paris 12 [UPEC UP12]
Maillot, Francois [Auteur]
Université de Tours [UT]
Ly, Kim-Heang [Auteur]
Besson, Gerard [Auteur]
Willems, Marjolaine [Auteur]
Labombarda, Fabien [Auteur]
Masseau, Agathe [Auteur]
Lavigne, Christian [Auteur]
Froissart, Roseline [Auteur]
Lacombe, Didier [Auteur]
Université de Bordeaux [UB]
Ziza, Jean-Marc [Auteur]
Hachulla, Eric [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Benveniste, Olivier [Auteur]
Centre de recherche en Myologie – U974 SU-INSERM
Centre de recherche en Myologie – U974 SU-INSERM
Lidove, Olivier [Auteur]
Centre de recherche en Myologie – U974 SU-INSERM
Amelin, Damien [Auteur]
Centre de recherche en Myologie – U974 SU-INSERM
Lamari, Foudil [Auteur]
Université Pierre et Marie Curie - Paris 6 [UPMC]
Caillaud, Catherine [Auteur]
Institut Necker Enfants-Malades [INEM - UM 111 (UMR 8253 / U1151)]
Mingozzi, Federico [Auteur]
Centre de recherche en Myologie – U974 SU-INSERM
Dzangue-Tchoupou, Gaelle [Auteur]
Centre de recherche en Myologie – U974 SU-INSERM
Arouche-Delaperche, Louiza [Auteur]
Centre de recherche en Myologie – U974 SU-INSERM
Douillard, Claire [Auteur]
Dussol, Bertrand [Auteur]
Aix Marseille Université [AMU]
Leguy-Seguin, Vanessa [Auteur]
D''halluin, Pauline [Auteur]
Université Francois Rabelais [Tours]
Noel, Esther [Auteur]
Zenone, Thierry [Auteur]
Matignon, Marie [Auteur]
Université Paris-Est Créteil Val-de-Marne - Paris 12 [UPEC UP12]
Maillot, Francois [Auteur]
Université de Tours [UT]
Ly, Kim-Heang [Auteur]
Besson, Gerard [Auteur]
Willems, Marjolaine [Auteur]
Labombarda, Fabien [Auteur]
Masseau, Agathe [Auteur]
Lavigne, Christian [Auteur]
Froissart, Roseline [Auteur]
Lacombe, Didier [Auteur]
Université de Bordeaux [UB]
Ziza, Jean-Marc [Auteur]
Hachulla, Eric [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Benveniste, Olivier [Auteur]
Centre de recherche en Myologie – U974 SU-INSERM
Titre de la revue :
Orphanet Journal of Rare Diseases
Nom court de la revue :
Orphanet J. Rare Dis.
Numéro :
13
Date de publication :
2018-07-31
ISSN :
1750-1172
Mot(s)-clé(s) :
Fabry disease
Anti-drug antibodies
Agalsidase
Lysosomal storage disease
Enzyme replacement therapy
IgG4
Anti-drug antibodies
Agalsidase
Lysosomal storage disease
Enzyme replacement therapy
IgG4
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
Background: Fabry disease (OMIM #301500) is an X-linked disorder caused by alpha-galactosidase A deficiency with two major clinical phenotypes: classic and non-classic of different prognosis. From 2001, enzyme replacement ...
Lire la suite >Background: Fabry disease (OMIM #301500) is an X-linked disorder caused by alpha-galactosidase A deficiency with two major clinical phenotypes: classic and non-classic of different prognosis. From 2001, enzyme replacement therapies (ERT) have been available. We aimed to determine the epidemiology and the functional characteristics of anti-drug antibodies. Patients from the French multicenter cohort FFABRY (n = 103 patients, 53 males) were prospectively screened for total anti-agalsidase IgG and IgG subclasses with a home-made enzyme-linked immunosorbent assay (ELISA), enzyme-inhibition assessed with neutralization assays and lysoGb3 plasma levels, and compared for clinical outcomes. Results: Among the patients exposed to agalsidase, 40% of men (n = 18/45) and 8% of women (n = 2/25) had antibodies with a complete cross-reactivity towards both ERTs. Antibodies developed preferentially in men with non-missense GLA mutations (relative risk 2.88, p = 0.006) and classic phenotype (58.6% (17/29) vs 6.7% (1/16), p = 0.0005). Specific anti-agalsidase IgG1 were the most frequently observed (16/18 men), but the highest concentrations were observed for IgG4 (median 1.89 μg/ml, interquartile range (IQR) [0.41–12.24]). In the men exposed to agalsidase, inhibition was correlated with the total IgG titer (r = 0.67, p < 0.0001), especially IgG4 (r = 0.75, p = 0.0005) and IgG2 (r = 0.72, p = 0.001). Inhibition was confirmed intracellularly in Fabry patient leucocytes cultured with IgG-positive versus negative serum (median: 42.0 vs 75.6%, p = 0.04), which was correlated with IgG2 (r = 0.67, p = 0.017, n = 12) and IgG4 levels (r = 0.59, p = 0.041, n = 12). Plasma LysoGb3 levels were correlated with total IgG (r = 0.66, p = 0.001), IgG2 (r = 0.72, p = 0.004), IgG4 (r = 0.58, p = 0.03) and IgG1 (r = 0.55, p = 0.04) titers. Within the classic group, no clinical difference was observed but lysoGb3 levels were higher in antibody-positive patients (median 33.2 ng/ml [IQR 20.6–55.6] vs 12.5 [10.1–24.0], p = 0.005). Conclusion: Anti-agalsidase antibodies preferentially develop in the severe classic Fabry phenotype. They are frequently associated with enzyme inhibition and higher lysoGb3 levels. As such, they could be considered as a hallmark of severity associated with the classic phenotype. The distinction of the clinical phenotypes should now be mandatory in studies dealing with Fabry disease and its current and future therapies.Lire moins >
Lire la suite >Background: Fabry disease (OMIM #301500) is an X-linked disorder caused by alpha-galactosidase A deficiency with two major clinical phenotypes: classic and non-classic of different prognosis. From 2001, enzyme replacement therapies (ERT) have been available. We aimed to determine the epidemiology and the functional characteristics of anti-drug antibodies. Patients from the French multicenter cohort FFABRY (n = 103 patients, 53 males) were prospectively screened for total anti-agalsidase IgG and IgG subclasses with a home-made enzyme-linked immunosorbent assay (ELISA), enzyme-inhibition assessed with neutralization assays and lysoGb3 plasma levels, and compared for clinical outcomes. Results: Among the patients exposed to agalsidase, 40% of men (n = 18/45) and 8% of women (n = 2/25) had antibodies with a complete cross-reactivity towards both ERTs. Antibodies developed preferentially in men with non-missense GLA mutations (relative risk 2.88, p = 0.006) and classic phenotype (58.6% (17/29) vs 6.7% (1/16), p = 0.0005). Specific anti-agalsidase IgG1 were the most frequently observed (16/18 men), but the highest concentrations were observed for IgG4 (median 1.89 μg/ml, interquartile range (IQR) [0.41–12.24]). In the men exposed to agalsidase, inhibition was correlated with the total IgG titer (r = 0.67, p < 0.0001), especially IgG4 (r = 0.75, p = 0.0005) and IgG2 (r = 0.72, p = 0.001). Inhibition was confirmed intracellularly in Fabry patient leucocytes cultured with IgG-positive versus negative serum (median: 42.0 vs 75.6%, p = 0.04), which was correlated with IgG2 (r = 0.67, p = 0.017, n = 12) and IgG4 levels (r = 0.59, p = 0.041, n = 12). Plasma LysoGb3 levels were correlated with total IgG (r = 0.66, p = 0.001), IgG2 (r = 0.72, p = 0.004), IgG4 (r = 0.58, p = 0.03) and IgG1 (r = 0.55, p = 0.04) titers. Within the classic group, no clinical difference was observed but lysoGb3 levels were higher in antibody-positive patients (median 33.2 ng/ml [IQR 20.6–55.6] vs 12.5 [10.1–24.0], p = 0.005). Conclusion: Anti-agalsidase antibodies preferentially develop in the severe classic Fabry phenotype. They are frequently associated with enzyme inhibition and higher lysoGb3 levels. As such, they could be considered as a hallmark of severity associated with the classic phenotype. The distinction of the clinical phenotypes should now be mandatory in studies dealing with Fabry disease and its current and future therapies.Lire moins >
Langue :
Anglais
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
Inserm
Université de Lille
CHU Lille
Université de Lille
CHU Lille
Équipe(s) de recherche :
Immunity, inflammation and fibrsis in auto and allo-reactivity
Date de dépôt :
2019-03-01T14:35:26Z
2024-01-25T11:35:00Z
2024-01-25T11:35:00Z
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