PuSH - Publication Server of Helmholtz Zentrum München: Antibodies against MLC1 found in patients with NMOSD-like disease mediate astrocytopathy in rodent models.

Navigation

Home

Deutsch

Research

Advanced Search

Browse by ...

... Journal

... Publication Type

... Research Data

... Publication Year

Publication overview

Support & Contact

Contact persons

Help

Data protection

Wong, H.K.* ; Ho, S.* ; Yu, Q.* ; Given, K.S.* ; Shqau, D.* ; Baier, S.* ; Winklmeier, S.* ; Rübsamen, H.* ; Kendirli, A.* ; Schanda, K.* ; Oswald, E.* ; Bräuer, K. ; Thaler, F.S.* ; Gerdes, L.A.* ; Feederle, R. ; Kerschensteiner, M.* ; Reindl, M.* ; Khademi, M.* ; Piehl, F.* ; Olsson, T.* ; Bennett, J.L.* ; Kümpfel, T.* ; Kawakami, N.* ; Bradl, M.* ; Meinl, E.* ; Mader, S.*

Antibodies against MLC1 found in patients with NMOSD-like disease mediate astrocytopathy in rodent models.

Sci. Transl. Med. 18:eady0403 (2026)

DOI

PMC

Abstract
Metrics
Extra information

The identification of autoantibodies against aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) has been essential in distinguishing neuromyelitis optica spectrum disorder (NMOSD) and MOG antibody-associated disease (MOGAD) from classical multiple sclerosis (MS), with important implications for treatment. However, for several patients within this disease spectrum, the target of the autoimmune response remains unknown. Here, we describe the modulator of VRAC current 1 (MLC1), a membrane protein with extracellular epitopes enriched at astrocytic end feet, as an autoantigen. Serum MLC1 antibodies were verified with a cell-based assay, identifying four MLC1 immunoglobulin G (IgG)-positive patients among 297 patients with inflammatory autoimmune diseases of the central nervous system who were screened. All four MLC1 IgG-positive patients exhibited overlapping yet atypical clinical features of MS and NMOSD and tested negative for AQP4 and MOG antibodies. Moreover, treatment with a monoclonal MLC1 antibody induced astrocytopathy in mouse cerebellar slice cultures and in a rat encephalitis model. Thus, MLC1 antibodies identify a subset of patients with an NMOSD-like phenotype, underscoring their potential as a disease marker with pathogenic relevance.

Altmetric

Additional Metrics?

[➜Log in]

Edit extra informations Login

Publication type Article: Journal article

Document type Scientific Article

Keywords Myelin Oligodendrocyte Glycoprotein ; Neuromyelitis Optica ; Autoantibody ; Multiple Sclerosis ; Antibody ; Epitope ; Oligodendrocyte ; Monoclonal Antibody ; Demyelinating Disease; Myelin-oligodendrocyte Glycoprotein; Multiple-sclerosis; Megalencephalic Leukoencephalopathy; Neuromyelitis-optica; Subcortical Cysts; Autoantibodies; Mog; Spectrum; Brain; Cells

ISSN (print) / ISBN 1946-6234

e-ISSN 1946-6242

Journal Science Translational Medicine

Quellenangaben Volume: 18, Issue: 864, Article Number: eady0403

Publisher American Association for the Advancement of Science (AAAS)

Publishing Place 1200 New York Ave, Nw, Washington, Dc 20005 Usa

Reviewing status Peer reviewed

Institute(s) Core Facility Monoclonal Antibodies (CF-MAB)

Grants NINDS
Else Kroener Fresenius Stiftung
Schering Stiftung and the Fritz Thyssen Foundation
DFG
Verein "Therapieforschung fur MS-Kranke e.V."
Austrian Science Fund (FWF)
Guthy-Jackson Charitable Foundation