Muscle regeneration failure may lead to clinical features of myopathy in anti-IgLON5 disease
Crijnen YS, Endmayr V, Franken SC, Van Der Beek NAME, Louter M, Ströbel T, Gelpi E, Koneczny I, Shigemoto R, Lewerenz J, Högl B, Wanschitz JV, Hofstadt-Van Oy UH, Van Steenhoven RW, Nagtzaam MMP, Kerstens J, Brenner J, Bastiaansen AEM, Verdijk RM, Van Den Bosch TPP, Schreurs M, Veenbergen S, Verbeek MM, Roelen DL, Guasp M, Sillevis Smitt PAE, Sabater L, De Vries JM, Höftberger R, Titulaer MJ. 2026. Muscle regeneration failure may lead to clinical features of myopathy in anti-IgLON5 disease. Neurology, Neuroimmunology & Neuroinflammation. 13(5), e200525.
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Journal Article
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Scopus indexed
Author
Crijnen, Yvette S.;
Endmayr, Verena;
Franken, Suzanne C.;
Van Der Beek, Nadine A.M.E.;
Louter, Maartje;
Ströbel, Thomas;
Gelpi, Ellen;
Koneczny, Inga;
Shigemoto, RyuichiISTA 
;
Lewerenz, Jan;
Högl, Birgit;
Wanschitz, Julia V.
All
;
Lewerenz, Jan;
Högl, Birgit;
Wanschitz, Julia V.
All
Department
Abstract
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.
Publishing Year
Date Published
2026-09-01
Journal Title
Neurology, Neuroimmunology & Neuroinflammation
Publisher
Wolters Kluwer
Acknowledgement
One author (Manuela Paunovic) was removed from the paper due to personal circumstances. Her contributions were removed from the manuscript before final review. The authors thank all patients for their participation and all referring physicians. The authors thank Professor Joachim Weis at the Medical Faculty RWTH Aachen University for his contribution to the manuscript. The authors would like to thank Andrea Polt and Irene Erber at the Medical University of Vienna, and Jacqueline Montanaro at IST Austria, for their assistance in the laboratory. N.A.M.E. van der Beek participates in EURO-NMD. M.W.J. Schreurs, P.A.E. Sillevis Smitt, J.M. de Vries, and M.J. Titulaer are members of the European Reference Network for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases–Project ID No 739543 (ERN-RITA; HCP Erasmus MC). IK was funded by the Austrian Science Fund (FWF, T996-B30). RS was funded by the Austrian Science Fund (FWF, SYNABS, I6565-B). JL was funded by German Federal Ministry of Education and Research (BMBF, Forschungsverbund CONNECT-GEN-
ERATE, 01 GM2208B). RvS was funded by AEA Seed Grant 2023 and InterAct Grant of Alzheimer Nederland 2023. LS was funded by Instituto de Salud Carlos III (ISCIII, PI21/ 00165) and the Networking Support Scheme funded from the European Union’s Horizon 2020 research and innovation program (EJP RD COFUND-EJP N° 825575). JdV was funded by AEA Seed Grant 2021. RH was funded by grants from the Austrian Science Fund (FWF, SYNABS, I4685-B, I6565-B), Forschungsf¨orderungsgesellschaft (FFG, IGNITE-
MIND, FO999920011), and the Austrian Society of
Neurology (
¨
Osterreichische Gesellschaft f¨ur Neurologie).
MT was funded by the Dutch EpilepsieNL Foundation (NEF 19-08), an Interlaken Leadership award, Dioraphte (2001 0403) the Dutch Research Council (ZonMW, PARADE-
VIMP) and E-RARE JTC 2018 (UltraAIE, 90030376505).
Volume
13
Issue
5
Page
e200525
eISSN
IST-REx-ID
Cite this
Crijnen YS, Endmayr V, Franken SC, et al. Muscle regeneration failure may lead to clinical features of myopathy in anti-IgLON5 disease. Neurology, Neuroimmunology & Neuroinflammation. 2026;13(5):e200525. doi:10.1212/NXI.0000000000200525
Crijnen, Y. S., Endmayr, V., Franken, S. C., Van Der Beek, N. A. M. E., Louter, M., Ströbel, T., … Titulaer, M. J. (2026). Muscle regeneration failure may lead to clinical features of myopathy in anti-IgLON5 disease. Neurology, Neuroimmunology & Neuroinflammation. Wolters Kluwer. https://doi.org/10.1212/NXI.0000000000200525
Crijnen, Yvette S., Verena Endmayr, Suzanne C. Franken, Nadine A.M.E. Van Der Beek, Maartje Louter, Thomas Ströbel, Ellen Gelpi, et al. “Muscle Regeneration Failure May Lead to Clinical Features of Myopathy in Anti-IgLON5 Disease.” Neurology, Neuroimmunology & Neuroinflammation. Wolters Kluwer, 2026. https://doi.org/10.1212/NXI.0000000000200525.
Y. S. Crijnen et al., “Muscle regeneration failure may lead to clinical features of myopathy in anti-IgLON5 disease,” Neurology, Neuroimmunology & Neuroinflammation, vol. 13, no. 5. Wolters Kluwer, p. e200525, 2026.
Crijnen YS, Endmayr V, Franken SC, Van Der Beek NAME, Louter M, Ströbel T, Gelpi E, Koneczny I, Shigemoto R, Lewerenz J, Högl B, Wanschitz JV, Hofstadt-Van Oy UH, Van Steenhoven RW, Nagtzaam MMP, Kerstens J, Brenner J, Bastiaansen AEM, Verdijk RM, Van Den Bosch TPP, Schreurs M, Veenbergen S, Verbeek MM, Roelen DL, Guasp M, Sillevis Smitt PAE, Sabater L, De Vries JM, Höftberger R, Titulaer MJ. 2026. Muscle regeneration failure may lead to clinical features of myopathy in anti-IgLON5 disease. Neurology, Neuroimmunology & Neuroinflammation. 13(5), e200525.
Crijnen, Yvette S., et al. “Muscle Regeneration Failure May Lead to Clinical Features of Myopathy in Anti-IgLON5 Disease.” Neurology, Neuroimmunology & Neuroinflammation, vol. 13, no. 5, Wolters Kluwer, 2026, p. e200525, doi:10.1212/NXI.0000000000200525.
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