دورية أكاديمية
JAK Inhibition in Aicardi-Goutières Syndrome: a Monocentric Multidisciplinary Real-World Approach Study
| العنوان: | JAK Inhibition in Aicardi-Goutières Syndrome: a Monocentric Multidisciplinary Real-World Approach Study |
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| المؤلفون: | Frémond, Marie-Louise, Hully, Marie, Fournier, Benjamin, Barrois, Rémi, Lévy, Romain, Aubart, Mélodie, Castelle, Martin, Chabalier, Delphine, Gins, Clarisse, Sarda, Eugénie, Al Adba, Buthaina, Couderc, Sophie, D’ Almeida, Céline, Berat, Claire-Marine, Durrleman, Chloé, Espil, Caroline, Lambert, Laetitia, Méni, Cécile, Périvier, Maximilien, Pillet, Pascal, Polivka, Laura, Schiff, Manuel, Todosi, Calina, Uettwiller, Florence, Lepelley, Alice, Rice, Gillian, I, Seabra, Luis, Sanquer, Sylvia, Hulin, Anne, Pressiat, Claire, Goldwirt, Lauriane, Bondet, Vincent, Duffy, Darragh, Moshous, Despina, Bader-Meunier, Brigitte, Bodemer, Christine, Robin-Renaldo, Florence, Boddaert, Nathalie, Blanche, Stéphane, Desguerre, Isabelle, Crow, Yanick, J, Neven, Bénédicte |
| المساهمون: | Hôpital Necker - Enfants Malades AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Neurogénétique et neuroinflammation = Neurogenetics and neuroinflammation (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Sidra Medicine Doha, Qatar, Centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS Poissy, Centre Hospitalier Intercommunal Castres-Mazamet (CHIC-CM), CHU Bordeaux, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University of Manchester Manchester, Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hopital Saint-Louis AP-HP (AP-HP), Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur Paris (IP)-Université Paris Cité (UPCité), CHU Trousseau APHP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Edinburgh (Edin.), Immunogenetics of pediatric autoimmune diseases (Equipe Inserm U1163), M.-L. F. received a grant from the Institut National de la Santé et de la Recherche Médicale (reference: 000427993). Y. J. C. acknowledges the European Research Council (GA309449 and 786142-E-T1IFNs) and a state subsidy managed by the National Research Agency (France) under the “Investments for the Future” program bearing the reference ANR-10-IAHU-01. Y. J. C. is supported by a UK Medical Research Council Human Genetics Unit core grant (MRC, U127580972). Y. J. C. and D. D. acknowledge the ANR (grant CE17001002). D. D. thanks ImmunoQure AG for the provision of antibodies for the Simoa assay. The project was supported by MSDAVENIR (Devo-Decode Project)., ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), European Project: 786142,ERC-2017-ADG,E-T1IFNs(2018) |
| المصدر: | ISSN: 0271-9142. |
| بيانات النشر: | HAL CCSD Springer Verlag |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Aicardi-Goutières syndrome (AGS), interferon, JAK inhibitors, [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; The paradigm type I interferonopathy Aicardi-Goutières syndrome (AGS) is most typically characterized by severe neurological involvement. AGS is considered an immune-mediated disease, poorly responsive to conventional immunosuppression. Premised on a chronic enhancement of type I interferon signaling, JAK1/2 inhibition has been trialed in AGS, with clear improvements in cutaneous and systemic disease manifestations. Contrastingly, treatment efficacy at the level of the neurological system has been less conclusive. Here, we report our real-word approach study of JAK1/2 inhibition in 11 patients with AGS, providing extensive assessments of clinical and radiological status; interferon signaling, including in cerebrospinal fluid (CSF); and drug concentrations in blood and CSF. Over a median follow-up of 17 months, we observed a clear benefit of JAK1/2 inhibition on certain systemic features of AGS, and reproduced results reported using the AGS neurologic severity scale. In contrast, there was no change in other scales assessing neurological status; using the caregiver scale, only patient comfort, but no other domain of everyday-life care, was improved. Serious bacterial infections occurred in 4 out of the 11 patients. Overall, our data lead us to conclude that other approaches to treatment are urgently required for the neurologic features of AGS. We suggest that earlier diagnosis and adequate central nervous system penetration likely remain the major factors determining the efficacy of therapy in preventing irreversible brain damage, implying the importance of early and rapid genetic testing and the consideration of intrathecal drug delivery. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/37171742; info:eu-repo/grantAgreement// 786142/EU/Elaboration of the type I interferonopathies/E-T1IFNs; pasteur-04124249; https://pasteur.hal.science/pasteur-04124249Test; https://pasteur.hal.science/pasteur-04124249/documentTest; https://pasteur.hal.science/pasteur-04124249/file/s10875-023-01500-z.pdfTest; PUBMED: 37171742; PUBMEDCENTRAL: PMC10175907 |
| DOI: | 10.1007/s10875-023-01500-z |
| الإتاحة: | https://doi.org/10.1007/s10875-023-01500-zTest https://pasteur.hal.science/pasteur-04124249Test https://pasteur.hal.science/pasteur-04124249/documentTest https://pasteur.hal.science/pasteur-04124249/file/s10875-023-01500-z.pdfTest |
| حقوق: | http://creativecommons.org/licenses/byTest/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.ACB62BAE |
| قاعدة البيانات: | BASE |
| DOI: | 10.1007/s10875-023-01500-z |
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