Muscle regeneration failure may lead to clinical features of myopathy in anti-IgLON5 disease Crijnen, Yvette S. Endmayr, Verena Franken, Suzanne C. Van Der Beek, Nadine A.M.E. Louter, Maartje Ströbel, Thomas Gelpi, Ellen Koneczny, Inga Shigemoto, Ryuichi ; https://orcid.org/0000-0001-8761-9444 Lewerenz, Jan Högl, Birgit Wanschitz, Julia V. Hofstadt-Van Oy, Ulrich He Van Steenhoven, Robin W. Nagtzaam, Mariska M.P. Kerstens, Jeroen Brenner, Juliette Bastiaansen, Anna E.M. Verdijk, Robert M. Van Den Bosch, Thierry P.P. Schreurs, Marco Veenbergen, Sharon Verbeek, Marcel M. Roelen, Dave L. Guasp, Mar Sillevis Smitt, Peter A.E. Sabater, Lidia De Vries, Juna M. Höftberger, Romana Titulaer, Maarten J. ddc:570 Background and Objectives: Anti-immunoglobulin-like cell adhesion molecule 5 (IgLON5) disease is a novel and poten- tially treatable entity. Therefore, it is important to recognize all clinical symptoms and di- agnostic clues. We specifically investigated neuromuscular signs and symptoms and muscle biopsy pathology, providing a link between IgLON5 and clinical features of myopathy. Methods: All patients diagnosed with anti-IgLON5 disease in the Netherlands between 2016 and 2023 were included. Serum and CSF samples were tested with immunohistochemistry on rat brain and in-house cell-based assay using live cells. Biopsies of the vastus lateralis muscle were performed in patients with neuromuscular signs and symptoms and analyzed in Vienna to- gether with 3 biopsies of non-Dutch patients sent to Vienna for second opinion. Results: Twenty patients with anti-IgLON5 disease were included (10 male, 50%). The median age at onset was 61.5 years (range 45–85), and the median time from onset to diagnosis was 30 months (range 3–280). Neuromuscular symptoms were present in over half of the patients (11/20), including proximal limb weakness (n = 11), axial weakness (n = 1), muscle atrophy (n = 6), and fasciculations (n = 5). All 12 muscle biopsies (9 from the Dutch cohort, 3 external) showed mild myopathic alterations, 2 additionally presented target fibers and fiber type grouping (compatible with neu- rogenic myopathy), and 3 patients showed immune cell infiltration. We found a strong upregulation of IgLON5 expression in muscle fibers in all patients and also in different muscle disease controls, while immunoreactivity in healthy control muscle was faint/absent. Discussion: Our data support that IgLON5 might play a role in muscle regeneration, which might result in proximal myopathy as a prominent clinical feature in anti-IgLON5 disease. This finding broadens the clinical phenotype of anti-IgLON5 disease and can be an important clue for earlier diagnosis and start of immunotherapy. Wolters Kluwer 2026 info:eu-repo/semantics/article doc-type:article text http://purl.org/coar/resource_type/c_2df8fbb1 https://research-explorer.ista.ac.at/record/22615 https://research-explorer.ista.ac.at/download/22615/22631 Crijnen YS, Endmayr V, Franken SC, et al. Muscle regeneration failure may lead to clinical features of myopathy in anti-IgLON5 disease. <i>Neurology, Neuroimmunology &#38; Neuroinflammation</i>. 2026;13(5):e200525. doi:<a href="https://doi.org/10.1212/NXI.0000000000200525">10.1212/NXI.0000000000200525</a> eng info:eu-repo/semantics/altIdentifier/doi/10.1212/NXI.0000000000200525 info:eu-repo/semantics/altIdentifier/e-issn/2332-7812 info:eu-repo/semantics/altIdentifier/pmid/42441930 info:eu-repo/semantics/openAccess