Immune signatures link myelin oligodendrocyte glycoprotein antibody–associated disease to other autoantibody-mediated conditions
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently defined neurological autoimmune condition. The pathogenesis of the disease remains poorly understood, and no specific therapies are currently approved. Here, a comprehensive single-cell immunophenotyping of peripheral blood mononuclear cells from two independent cohorts of patients with MOGAD revealed pronounced immune perturbations in MOGAD when compared with healthy controls and patients with multiple sclerosis. Patients with MOGAD displayed an expansion of CXCR5<sup>-</sup>CD21<sup>-</sup> activated naïve and double-negative B cell subsets, a feature shared with patients with systemic lupus erythematosus. In addition, we observed altered Fc gamma receptor expression in natural killer cells, monocytes, and dendritic cells. Within the T cell compartment, CXCR3<sup>+</sup>CD4<sup>+</sup> memory T cells were reduced in the circulation of patients with MOGAD compared with healthy controls, and this result was mirrored in a transgenic mouse model that showed retention of these cells in the inflamed central nervous system. Together, these results demonstrate profound systemic immune cell alterations in MOGAD and contribute to a better understanding of this distinct disease entity.
Authors
- Ana Beatriz Ayroza Galvão Ribeiro Gomes (ORCID: https://orcid.org/0000-0003-1657-6891)
- Laila Kulsvehagen (ORCID: https://orcid.org/0000-0001-5236-8323)
- Sofia Tyystjärvi (ORCID: https://orcid.org/0000-0002-5057-1923)
- Victor Kreiner (ORCID: https://orcid.org/0000-0002-7784-9286)
- Roland Liblau (ORCID: https://orcid.org/0000-0001-5477-5475)
- Donatella De Feo (ORCID: https://orcid.org/0000-0003-0121-5364)
- Stefanie Kreutmair (ORCID: https://orcid.org/0000-0001-8466-6675)
- Burkhard Becher (ORCID: https://orcid.org/0000-0002-1541-7867)
- Laura Power (ORCID: https://orcid.org/0000-0001-7913-931X)
- Susanne Unger (ORCID: https://orcid.org/0000-0001-6916-7544)
- Can Ulutekin (ORCID: https://orcid.org/0000-0003-4406-5423)
- Nicolás Gonzalo Núñez (ORCID: https://orcid.org/0000-0003-3837-270X)
- Thomas Korn (ORCID: https://orcid.org/0000-0002-3633-0955)
- Patrick Lipps (ORCID: https://orcid.org/0009-0002-5910-7622)
- Florian Ingelfinger (ORCID: https://orcid.org/0000-0001-6890-9753)
- Jonas Schmid (ORCID: https://orcid.org/0000-0001-9105-9144)
- Camille Chaubet
- Anne‐Katrin Pröbstel (ORCID: https://orcid.org/0000-0002-7748-1872)
- Stijn Swinnen (ORCID: https://orcid.org/0000-0003-1028-197X)
- Romain Marignier (ORCID: https://orcid.org/0000-0002-5967-2800)
- Chiara Alberti (ORCID: https://orcid.org/0000-0002-6857-9261)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Allen Institute for Brain Science (US)
- Inserm (FR)
- Université Fédérale de Toulouse Midi-Pyrénées (FR)
- University of Zurich (CH)
- University Hospital Bonn (DE)
- German Center for Neurodegenerative Diseases (DE)
- University Hospital of Basel (CH)
- Centre de Recherche en Neurosciences de Lyon (FR)
- University Hospital of Zurich (CH)
- Research Centre in Biological Chemistry of Córdoba (AR)
- Munich Cluster for Systems Neurology (DE)
- Life Science Zurich (CH)
- Department of Biomedicine Basel (CH)
- Centro Científico Tecnológico - Córdoba (AR)
- Institute of Neuroimmunology of the Slovak Academy of Sciences (SK)
- Institut des Maladies Métaboliques et Cardiovasculaires (FR)
- VIB-KU Leuven Center for Brain & Disease Research (BE)
- KU Leuven (BE)
Publication Details
- Journal
- Science Translational Medicine
- Published
- 2025-10-08
- DOI
- https://doi.org/10.1126/scitranslmed.adw0358
- Citations
- 1
- Primary Topic
- Systemic Lupus Erythematosus Research
- Type
- article
- Field-Weighted Citation Impact
- 1.67