Perturbed Microbiota/Immune Homeostasis in Multiple Sclerosis
| العنوان: | Perturbed Microbiota/Immune Homeostasis in Multiple Sclerosis |
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| المؤلفون: | Catherine Juste, Catherine Lubetzki, Marina Vignes, Gaëlle Autaa, Romain Deschamps, Jennifer Aboab, Caroline Papeix, Christophe Parizot, Patricia Lepage, Karim Dorgham, Jehane Fadlallah, Savine Vicart, Guy Gorochov, Delphine Sterlin, Martin Larsen, Olivier Gout, Elisabeth Maillart |
| المساهمون: | HAL-SU, Gestionnaire, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) |
| المصدر: | Neurology Neuroimmunology & Neuroinflammation Neurology Neuroimmunology & Neuroinflammation, 2021, 8 (4), pp.e997. ⟨10.1212/nxi.0000000000000997⟩ Neurology® Neuroimmunology & Neuroinflammation article-version (Version of Record) 3 Neurology Neuroimmunology & Neuroinflammation, American Academy of neurology, 2021, 8 (4), pp.e997. ⟨10.1212/nxi.0000000000000997⟩ |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Adult, Male, Multiple Sclerosis, Adolescent, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Context (language use), Gut flora, digestive system, Article, Flow cytometry, Young Adult, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Immune system, Immunity, RNA, Ribosomal, 16S, medicine, Homeostasis, Humans, 030304 developmental biology, 0303 health sciences, biology, medicine.diagnostic_test, business.industry, Microbiota, Multiple sclerosis, Patient Acuity, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Middle Aged, medicine.disease, biology.organism_classification, Commensalism, Gastrointestinal Microbiome, Immunoglobulin A, 3. Good health, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Neurology, Immunoglobulin G, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, Immunology, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Bacteria |
| الوصف: | ObjectiveBased on animal models and human studies, there is now strong suspicion that host/microbiota mutualism in the context of gut microbial dysbiosis could influence immunity and multiple sclerosis (MS) evolution. Our goal was to seek evidence of deregulated microbiota-induced systemic immune responses in patients with MS.MethodsWe investigated gut and systemic commensal-specific antibody responses in healthy controls (n = 32), patients with relapsing-remitting MS (n = 30), and individuals with clinically isolated syndromes (CISs) (n = 15). Gut microbiota composition and diversity were compared between controls and patients by analysis of 16S ribosomal ribonucleic acid (rRNA) sequencing. Autologous microbiota and cultivable bacterial strains were used in bacterial flow cytometry assays to quantify autologous serum IgG and secretory IgA responses to microbiota. IgG-bound bacteria were sorted by flow cytometry and identified using 16S rRNA sequencing.ResultsWe show that commensal-specific gut IgA responses are drastically reduced in patients with severe MS, disease severity being correlated with the IgA-coated fecal microbiota fraction (r = −0.647, p < 0.0001). At the same time, IgA-unbound bacteria elicit qualitatively broad and quantitatively increased serum IgG responses in patients with MS and CIS compared with controls (4.1% and 2.5% vs 1.9%, respectively, p < 0.001).ConclusionsGut and systemic microbiota/immune homeostasis are perturbed in MS. Our results argue that defective IgA responses in MS are linked to a breakdown of systemic tolerance to gut microbiota leading to an enhanced triggering of systemic IgG immunity against gut commensals occurring early in MS. |
| وصف الملف: | application/pdf |
| تدمد: | 2332-7812 |
| DOI: | 10.1212/nxi.0000000000000997 |
| DOI: | 10.1212/nxi.0000000000000997⟩ |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::097ddc44c26470d354f785086b21cc23 https://doi.org/10.1212/nxi.0000000000000997 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....097ddc44c26470d354f785086b21cc23 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23327812 |
|---|---|
| DOI: | 10.1212/nxi.0000000000000997 |