Prevalence and long-term monitoring of humoral immunity against adeno-associated virus in Duchenne Muscular Dystrophy patients

Autor: Olivier Boyer, Fabienne Jouen, Virginie Latournerie, Carole Masurier, Marcelo Simon Sola, Federico Mingozzi, Diana Desgue, Severine Charles, Philippe Veron, Aliénor Quéré, Elisa Masat, Christian Leborgne, Elodie Pignot, Sylvie Boutin, Fanny Collaud
Přispěvatelé: Généthon, Approches génétiques intégrées et nouvelles thérapies pour les maladies rares (INTEGRARE), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Centre de recherche en myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Généthon, Evry, Centre de recherche et d'applications sur les thérapies géniques (CRATG), Université d'Évry-Val-d'Essonne (UEVE)-GENETHON 3-Centre National de la Recherche Scientifique (CNRS), École pratique des hautes études (EPHE)-Université d'Évry-Val-d'Essonne (UEVE)-GENETHON 3-Institut National de la Santé et de la Recherche Médicale (INSERM), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Immunologie moléculaire et biothérapies innovantes, École pratique des hautes études (EPHE)-Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Genethon, Laboratoire des Sciences de l'Information et des Systèmes (LSIS), Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Arts et Métiers Paristech ENSAM Aix-en-Provence-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Adult
AAV humoral immunity
Adolescent
Duchenne muscular dystrophy
Genetic enhancement
[SDV]Life Sciences [q-bio]
viruses
Immunology
Genetic Vectors
Duchenne Muscular Dystrophy
Biology
medicine.disease_cause
Antibodies
Viral
Virus
Cohort Studies
03 medical and health sciences
Young Adult
0302 clinical medicine
Gene therapy
Seroepidemiologic Studies
medicine
Humans
Longitudinal Studies
Seroconversion
Adeno-associated virus
ComputingMilieux_MISCELLANEOUS
Immunosuppression Therapy
Antibody titer
Age Factors
Dependovirus
medicine.disease
Antibodies
Neutralizing
3. Good health
Immunity
Humoral
Muscular Dystrophy
Duchenne
030104 developmental biology
[SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology
Immunoglobulin G
Humoral immunity
biology.protein
[SDV.IMM]Life Sciences [q-bio]/Immunology
Antibody
030215 immunology
Zdroj: Cellular Immunology
Cellular Immunology, Elsevier, 2018, pp.103780. ⟨10.1016/j.cellimm.2018.03.004⟩
Cellular Immunology, 2018, pp.103780. ⟨10.1016/j.cellimm.2018.03.004⟩
Cellular Immunology, Elsevier, 2019, 342, pp.103780. ⟨10.1016/j.cellimm.2018.03.004⟩
ISSN: 0008-8749
1090-2163
Popis: International audience; Adeno-associated virus (AAV) vectors are promising candidates for gene therapy and have been explored as gene delivery vehicles in the treatment of Duchenne Muscular Dystrophy (DMD). Recent studies showed compelling evidence of therapeutic efficacy in large animal models following the intravenous delivery of AAV vectors expressing truncated forms of dystrophin. However, to translate these results to humans, careful assessment of the prevalence of anti-AAV neutralizing antibodies (NAbs) is needed, as presence of preexisting NABs to AAV in serum have been associated with a drastic diminution of vector transduction. Here we measured binding and neutralizing antibodies against AAV serotype 1, 2, and 8 in serum from children and young adults with DMD (n = 130). Results were compared with to age-matched healthy donors (HD, n = 113). Overall, approximately 54% of all subjects included in the study presented IgG to AAV2, 49% to AAV1, and 41% to AAV8. A mean of around 80% of IgG positive sera showed neutralizing activity with no statistical difference between DMD and HD. NAb titers for AAV2 were higher than AAV1, and AAV8 in both populations studied. Older DMD patients (13-24 years old) presented significantly lower anti-AAV8 IgG4 subclass. Anti-AAV antibodies were found to be decreased in DMD patients subjected to a 6-month course of corticosteroids and in subjects receiving a variety of immunosuppressive drugs including B cell targeting drugs. Longitudinal follow up of humoral responses to AAV over up to 6 years showed no change in antibody titers, suggesting that in this patient population, seroconversion is a rare event in humans.
Databáze: OpenAIRE
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