Abstract
Neurofilament light chain (NfL) is a sensitive biomarker of axonal damage, but its clinical relevance in chronic autoimmune neuropathies remains incompletely defined. This study evaluated plasma NfL levels in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN), compared with hereditary neuropathy (Charcot–Marie–Tooth disease type 1 A, CMT1A) and healthy controls, focusing on disease activity rather than diagnostic discrimination. Plasma NfL concentrations were measured using single molecule array (Simoa) technology in 41 patients (CIDP n = 16, MMN n = 7, CMT1A n = 18) and 25 age- and sex-matched controls. Disease severity was assessed using the Inflammatory Rasch-built Overall Disability Scale for autoimmune neuropathies and the Charcot–Marie–Tooth Neuropathy Score version 2 for CMT. Plasma NfL levels were significantly higher in patients with autoimmune neuropathies and CMT compared with controls. No significant differences were observed between inflammatory and hereditary neuropathies, and NfL levels did not correlate with disability scores. However, patients with autoimmune neuropathies and an unstable disease course, defined by more than two relapses, exhibited significantly higher plasma NfL levels. Across all groups, NfL concentrations showed a strong correlation with age. These findings suggest that while plasma NfL lacks diagnostic specificity among chronic neuropathies, it may be associated with disease instability in autoimmune neuropathies.
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The raw data supporting the conclusions of this article will be made available by the authors upon a reasonable request.
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Acknowledgements
HZ is a Wallenberg Scholar and a Distinguished Professor at the Swedish Research Council supported by grants from the Swedish Research Council (#2023 − 00356; #2022 − 01018 and #2019–02397), the European Union’s Horizon Europe research and innovation programme under grant agreement No 101053962, Swedish State Support for Clinical Research (#ALFGBG-71320), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809–2016862), the AD Strategic Fund and the Alzheimer’s Association (#ADSF-21-831376-C, #ADSF-21-831381-C, #ADSF-21-831377-C, and #ADSF-24-1284328-C), the European Partnership on Metrology, co-financed from the European Union’s Horizon Europe Research and Innovation Programme and by the Participating States (NEuroBioStand, #22HLT07), the Bluefield Project, Cure Alzheimer’s Fund, the Olav Thon Foundation, the Erling-Persson Family Foundation, Familjen Rönströms Stiftelse, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2022-0270), the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE), the European Union Joint Programme – Neurodegenerative Disease Research (JPND2021-00694), the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, and the UK Dementia Research Institute at UCL (UKDRI-1003).
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IG and VK conceived and designed the study. IG, MR, VŽ, and NK contributed to patient recruitment and clinical data collection. IG and VK performed statistical analyses and drafted the first version of the manuscript. Plasma NfL measurements and analytical procedures were performed under the supervision of KB and HZ. VK supervised the project and provided clinical oversight. All authors contributed to interpretation of the results, critically revised the manuscript for important intellectual content, and approved the final version of the manuscript.
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Glāzere, I., Roddate, M., Žukova, V. et al. Plasma neurofilament light chain is associated with clinical instability in chronic autoimmune neuropathies. Sci Rep (2026). https://doi.org/10.1038/s41598-026-39803-x
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DOI: https://doi.org/10.1038/s41598-026-39803-x
