{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:40:16Z","timestamp":1792172416253,"version":"4.4.0"},"reference-count":33,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:00:00Z","timestamp":1755216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Research Council Advanced Grant","award":["340733"],"award-info":[{"award-number":["340733"]}]},{"name":"Clinical Research Priority Programs (CRPPs) \u201cHeterogeneity MS\u201d and \u201cPrecision MS\u201d of the University Zurich","award":["340733"],"award-info":[{"award-number":["340733"]}]},{"name":"Clinical, Swiss National Science Foundation (Sinergia UnmetMS)","award":["340733"],"award-info":[{"award-number":["340733"]}]},{"name":"Swiss MS Society","award":["340733"],"award-info":[{"award-number":["340733"]}]},{"name":"Region Pays de la Loire","award":["340733"],"award-info":[{"award-number":["340733"]}]},{"name":"ANTARES","award":["340733"],"award-info":[{"award-number":["340733"]}]},{"name":"FranceSEP","award":["340733"],"award-info":[{"award-number":["340733"]}]},{"name":"NotreScl\u00e9rose","award":["340733"],"award-info":[{"award-number":["340733"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Gut microbial dysbiosis, leaky gut, and increased transepithelial translocation of commensal bacteria have been documented in multiple sclerosis (MS). Intrathecal IgGs specific for Akkermansia muciniphila, a gut bacterium, are increased in patients with MS and associated with clinical disability. Our objective here was to explore the putative involvement of intrathecal anti-A. muciniphila IgG in MS pathogenesis by characterizing patients with different anti-A. muciniphila IgG indices. Methods: Serum and intrathecal IgG specific for A. muciniphila and other gut bacteria, as well as routine cerebrospinal fluid (CSF) parameters, were measured in 61 patients with MS. Examination of these patients included immunophenotyping of CSF-infiltrating and paired circulating lymphocytes, intrathecal markers of neurodegeneration and inflammation, and a detailed characterization of demographic, clinical, and magnetic resonance imaging (MRI) features. Results: Plasma blasts (p &lt; 0.01), B cells (p &lt; 0.01), and Th2 cells (p &lt; 0.01), which might be involved in antibody production, were increased in the CSF of these patients, as well as blood pro-inflammatory Th17 cells (p &lt; 0.05). Anti-A. muciniphila IgG indices were negatively associated with blood-brain barrier (BBB) permeability and circulating monocytes (p &lt; 0.001), and positively with brain lesion load (p &lt; 0.01). Conclusions: The differences between patients with low and high anti-A. muciniphila IgG indexes regarding BBB permeability, CSF cell infiltrates, and pro-inflammatory peripheral immune cells, as well as imaging features, support a role of anti-A. muciniphila immune response in MS pathogenesis.<\/jats:p>","DOI":"10.3390\/jcm14165771","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T08:39:07Z","timestamp":1755247147000},"page":"5771","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Intrathecal Anti-Akkermansia muciniphila IgG Responses in Multiple Sclerosis Patients Linked to CSF Immune Cells and Disease Activity"],"prefix":"10.3390","volume":"14","author":[{"given":"Carolina","family":"Cruciani","sequence":"first","affiliation":[{"name":"Neuroimmunology and MS Research (NIMS), Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Math\u00e9","sequence":"additional","affiliation":[{"name":"Centre de Recherche Translationnelle en Transplantation et Immunologie, CR2TI UMR1064, Inserm, Universit\u00e9 de Nantes, CHU de Nantes, CEDEX 01, 44093 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2313-8462","authenticated-orcid":false,"given":"Marco","family":"Puthenparampil","sequence":"additional","affiliation":[{"name":"Neuroimmunology and MS Research (NIMS), Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091 Z\u00fcrich, Switzerland"},{"name":"Department of Neuroscience DNS, University Hospital of Padova, Via Giustiniani, 5, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Tomas-Ojer","sequence":"additional","affiliation":[{"name":"Neuroimmunology and MS Research (NIMS), Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1242-222X","authenticated-orcid":false,"given":"Maria Jos\u00e9","family":"Docampo","sequence":"additional","affiliation":[{"name":"Neuroimmunology and MS Research (NIMS), Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Opfer","sequence":"additional","affiliation":[{"name":"Jung Diagnostics GmbH, HIP\u2014Health Innovation Port, R\u00f6ntgenstra\u00dfe 24, 22335 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3090-7319","authenticated-orcid":false,"given":"Ilijas","family":"Jelcic","sequence":"additional","affiliation":[{"name":"Neuroimmunology and MS Research (NIMS), Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2695-3304","authenticated-orcid":false,"given":"Arnaud B.","family":"Nicot","sequence":"additional","affiliation":[{"name":"Centre de Recherche Translationnelle en Transplantation et Immunologie, CR2TI UMR1064, Inserm, Universit\u00e9 de Nantes, CHU de Nantes, CEDEX 01, 44093 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David-Axel","family":"Laplaud","sequence":"additional","affiliation":[{"name":"Centre de Recherche Translationnelle en Transplantation et Immunologie, CR2TI UMR1064, Inserm, Universit\u00e9 de Nantes, CHU de Nantes, CEDEX 01, 44093 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0982-1329","authenticated-orcid":false,"given":"Roland","family":"Martin","sequence":"additional","affiliation":[{"name":"Neuroimmunology and MS Research (NIMS), Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireia","family":"Sospedra","sequence":"additional","affiliation":[{"name":"Neuroimmunology and MS Research (NIMS), Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9306-9247","authenticated-orcid":false,"given":"Laureline","family":"Berthelot","sequence":"additional","affiliation":[{"name":"Centre de Recherche Translationnelle en Transplantation et Immunologie, CR2TI UMR1064, Inserm, Universit\u00e9 de Nantes, CHU de Nantes, CEDEX 01, 44093 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/S1474-4422(21)00063-6","article-title":"Cellular immunology of relapsing multiple sclerosis: Interactions, checks, and balances","volume":"20","author":"Li","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/s41582-022-00700-2","article-title":"Pathogenic autoantibodies in multiple sclerosis\u2014From a simple idea to a complex concept","volume":"18","author":"Hoftberger","year":"2022","journal-title":"Nat. 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