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Association of serum neurofilament light chain levels with clinicopathology of chronic inflammatory demyelinating polyneuropathy, including NF155 reactive patients

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Abstract

Objectives

To clarify whether serum neurofilament light chains (NfLs) serve as a biomarker of axonal damage in patients with chronic inflammatory demyelinating polyneuropathy (CIDP), especially in patients with anti-neurofascin 155 (NF155) antibodies.

Methods

The Simoa system was used to examine serum NfL levels from 58 patients with CIDP, including 13 anti-NF155 antibody-positive patients, and from 14 age- and sex-matched healthy individuals. Serum NfL levels were evaluated before and after treatment in eight patients with anti-NF155 antibodies. Clinical features, electrophysiological findings, and cerebrospinal fluid (CSF) protein levels, were evaluated. The pathological features of sural nerves from 40 patients were also examined.

Results

Serum NfL levels were significantly higher in patients with CIDP than in healthy individuals (median 29.63 vs. 7.71 pg/mL, p < 0.001) and were correlated with both modified Rankin Scale scores (r = 0.584, p < 0.001) and CSF protein levels (r = 0.432, p = 0.001). The NfL levels of anti-NF155 antibody-positive patients were higher than those of antibody-negative patients (p = 0.005). Serum NfL levels were negatively correlated with compound muscle action potential amplitudes of the tibial nerves (r =  − 0.404, p = 0.004) and positively correlated with the degree of active axonal degeneration in the pathological findings (r = 0.485, p = 0.001). In the antibody-positive group, NfL levels and antibody titers decreased after treatment in all examined patients.

Conclusion

Serum NfL correlated with pathological indices of axonal degeneration, and may serve as a biomarker that reflects active axonal damage of CIDP.

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Data availability

The data that support the findings are available from the corresponding author upon reasonable request.

References

  1. Dyck PJ, Lais AC, Ohta M et al (1975) Chronic inflammatory polyradiculoneuropathy. Mayo Clin Proc 50(11):621–637

    CAS  PubMed  Google Scholar 

  2. Van den Bergh PY, Hadden RD, Bouche P et al (2010) European Federation of neurological societies/peripheral nerve society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint Task Force of the European Federation of Neurological societies and the peripheral nerve society – first revision. J Peripher Nerv Syst 15(3):185–195

    Article  Google Scholar 

  3. Dalakas MC (2011) Advances in the diagnosis, pathogenesis and treatment of CIDP. Nat Rev Neurol 7(9):507–517

    Article  Google Scholar 

  4. Latov N (2014) Diagnosis and treatment of chronic acquired demyelinating polyneuropathies. Nat Rev Neurol 10(8):435–446

    Article  CAS  Google Scholar 

  5. Bunschoten C, Jacobs BC, Van den Bergh PYK et al (2019) Progress in diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy. Lancet Neurol 18(8):784–794

    Article  CAS  Google Scholar 

  6. Koike H, Katsuno M (2020) Pathophysiology of chronic inflammatory demyelinating polyneuropathy: insights into classification and therapeutic strategy. Neurol Ther. https://doi.org/10.1007/s40120-020-00190-8

    Article  PubMed  PubMed Central  Google Scholar 

  7. Ng JK, Malotka J, Kawakami N et al (2012) Neurofascin as a target for autoantibodies in peripheral neuropathies. Neurology 79(23):2241–2248

    Article  CAS  Google Scholar 

  8. Querol L, Nogales-Gadea G, Rojas-Garcia R et al (2013) Antibodies to contactin-1 in chronic inflammatory demyelinating polyneuropathy. Ann Neurol 73(3):370–380

    Article  CAS  Google Scholar 

  9. Querol L, Nogales-Gadea G, Rojas-Garcia R et al (2014) Neurofascin IgG4 antibodies in CIDP associate with disabling tremor and poor response to IVIg. Neurology 82(10):879–886

    Article  CAS  Google Scholar 

  10. Doppler K, Appeltshauser L, Wilhelmi K et al (2015) Destruction of paranodal architecture in inflammatory neuropathy with anti-contactin-1 autoantibodies. J Neurol Neurosurg Psychiatry 86(7):720–728

    Article  Google Scholar 

  11. Miura Y, Devaux JJ, Fukami Y et al (2015) Contactin 1 IgG4 associates to chronic inflammatory demyelinating polyneuropathy with sensory ataxia. Brain 138(6):1484–1491

    Article  Google Scholar 

  12. Ogata H, Yamasaki R, Hiwatashi A et al (2015) Characterization of IgG4 anti-neurofascin 155 antibody-positive polyneuropathy. Ann Clin Transl Neurol 2(10):960–971

    Article  CAS  Google Scholar 

  13. Devaux JJ, Miura Y, Fukami Y et al (2016) Neurofascin-155 IgG4 in chronic inflammatory demyelinating polyneuropathy. Neurology 86(9):800–807

    Article  CAS  Google Scholar 

  14. Koike H, Kadoya M, Kaida KI et al (2017) Paranodal dissection in chronic inflammatory demyelinating polyneuropathy with anti-neurofascin-155 and anti-contactin-1 antibodies. J Neurol Neurosurg Psychiatry 88(6):465–473

    Article  Google Scholar 

  15. Vallat JM, Yuki N, Sekiguchi K et al (2017) Paranodal lesions in chronic inflammatory demyelinating polyneuropathy associated with anti-Neurofascin 155 antibodies. Neuromuscul Disord 27(3):290–293

    Article  Google Scholar 

  16. Koike H, Nishi R, Ikeda S et al (2018) Ultrastructural mechanisms of macrophage-induced demyelination in CIDP. Neurology 91(23):1051–1060

    Article  CAS  Google Scholar 

  17. Iijima M, Yamamoto M, Hirayama M et al (2005) Clinical and electrophysiologic correlates of IVIg responsiveness in CIDP. Neurology 64(8):1471–1475

    Article  CAS  Google Scholar 

  18. Rajabally YA (2015) Long-term immunoglobulin therapy for chronic inflammatory demyelinating polyradiculoneuropathy. Muscle Nerve 51(5):657–661

    Article  CAS  Google Scholar 

  19. Notturno F, Capasso M, DeLauretis A et al (2009) Glial fibrillary acidic protein as a marker of axonal damage in chronic neuropathies. Muscle Nerve 40(1):50–54

    Article  CAS  Google Scholar 

  20. Wong AH, Fukami Y, Sudo M et al (2016) Sialylated IgG-Fc: a novel biomarker of chronic inflammatory demyelinating polyneuropathy. J Neurol Neurosurg Psychiatry 87(3):275–279

    Article  Google Scholar 

  21. Allen JA, Merkies ISJ, Lewis RA (2020) Monitoring clinical course and treatment response in chronic inflammatory demyelinating polyneuropathy during routine care: a review of clinical and laboratory assessment measures. JAMA Neurol 77(9):1159–1166

    Article  Google Scholar 

  22. Lu CH, Macdonald-Wallis C, Gray E et al (2015) Neurofilament light chain: a prognostic biomarker in amyotrophic lateral sclerosis. Neurology 84(22):2247–2257

    Article  CAS  Google Scholar 

  23. Steinacker P, Feneberg E, Weishaupt J et al (2016) Neurofilaments in the diagnosis of motoneuron diseases: a prospective study on 455 patients. J Neurol Neurosurg Psychiatry 87(1):12–20

    PubMed  Google Scholar 

  24. Preische O, Schultz SA, Apel A et al (2019) Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease. Nat Med 25(2):277–283

    Article  CAS  Google Scholar 

  25. Mattsson N, Andreasson U, Zetterberg H et al (2017) Alzheimer’s disease neuroimaging initiative. Association of plasma neurofilament light with neurodegeneration in with alzheimer disease. JAMA Neurol 74(5):557–566

    Article  Google Scholar 

  26. Lycke JN, Karlsson JE, Andersen O et al (1998) Neurofilament protein in cerebrospinal fluid: a potential marker of activity in multiple sclerosis. J Neurol Neurosurg Psychiatry 64(3):402–404

    Article  CAS  Google Scholar 

  27. Malmeström C, Haghighi S, Rosengren L et al (2003) Neurofilament light protein and glial fibrillary acidic protein as biological markers in MS. Neurology 61(12):1720–1725

    Article  Google Scholar 

  28. Gunnarsson M, Malmeström C, Axelsson M et al (2011) Axonal damage in relapsing multiple sclerosis is markedly reduced by natalizumab. Ann Neurol 69(1):83–89

    Article  CAS  Google Scholar 

  29. Kuhle J, Kropshofer H, Haering DA et al (2019) Blood neurofilament light chain as a biomarker of MS disease activity and treatment response. Neurology 92(10):e1007–e1015

    Article  CAS  Google Scholar 

  30. Sandelius Å, Zetterberg H, Blennow K et al (2018) Plasma neurofilament light chain concentration in the inherited peripheral neuropathies. Neurology 90(6):e518–e524

    Article  CAS  Google Scholar 

  31. Mariotto S, Farinazzo A, Magliozzi R et al (2018) Serum and cerebrospinal neurofilament light chain levels in patients with acquired peripheral neuropathies. J Peripher Nerv Syst 23(3):174–177

    Article  CAS  Google Scholar 

  32. van Lieverloo GGA, Wieske L, Verhamme C et al (2019) Serum neurofilament light chain in chronic inflammatory demyelinating polyneuropathy. J Peripher Nerv Syst 24(2):187–194

    Article  Google Scholar 

  33. Ikeda S, Koike H, Nishi R et al (2019) Clinicopathological characteristics of subtypes of chronic inflammatory demyelinating polyradiculoneuropathy. J Neurol Neurosurg Psychiatry 90(9):988–996

    Article  Google Scholar 

  34. Dyck PJ, Dyck PJB, Engelstad J (2005) Pathologic alterations of nerves. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy, 4th edn. Elsevier, pp 733–829

    Chapter  Google Scholar 

  35. Gafson AR, Barthélemy NR, Bomont P et al (2020) Neurofilaments: neurobiological foundations for biomarker applications. Brain 143(7):1975–1998

    Article  Google Scholar 

  36. Lombardi V, Querin G, Ziff OJ et al (2019) Muscle and not neuronal biomarkers correlate with severity in spinal and bulbar muscular atrophy. Neurology 92(11):e1205–e1211

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Kapoor M, Foiani M, Heslegrave A et al (2019) Plasma neurofilament light chain concentration is increased and correlates with the severity of neuropathy in hereditary transthyretin amyloidosis. J Peripher Nerv Syst 24(4):314–319

    Article  CAS  Google Scholar 

  38. Shimizu F, Sawai S, Sano Y et al (2014) Severity and patterns of blood-nerve barrier breakdown in patients with chronic inflammatory demyelinating polyradiculoneuropathy: correlations with clinical subtypes. PLoS ONE 9(8):e104205

    Article  Google Scholar 

  39. Mariotto S, Carta S, Bozzetti S et al (2020) Sural nerve biopsy: current role and comparison with serum neurofilament light chain levels. J Neurol 267(10):2881–2887

    Article  CAS  Google Scholar 

  40. Fujita A, Ogata H, Yamasaki R et al (2018) Parallel fluctuation of anti-neurofascin 155 antibody levels with clinico-electrophysiological findings in patients with chronic inflammatory demyelinating polyradiculoneuropathy. J Neurol Sci 384:107–112

    Article  CAS  Google Scholar 

  41. Shimizu S, Iijima M, Fukami Y et al (2020) Efficacy and safety of rituximab in refractory CIDP with or without IgG4 autoantibodies (RECIPE): protocol for a double-blind, randomized Placebo-Controlled Clinical Trial. JMIR Res Protoc 9(4):e17117

    Article  Google Scholar 

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Acknowledgements

We thank Bronwen Gardner, PhD, from Edanz Group (https://en-author-services.edanzgroup.com/) for editing a draft of this manuscript.

Funding

Dr. Fukami, Dr. Koike, Dr. Yamada and Dr. Hashizume report no disclosures. Dr. Iijima is supported by grants by JSPS KAKENHI (JP20K07864), the Japan Agency for Medical Research and Development (20lk0201080), Zenyaku Kogyo Co. Ltd., and Japan Blood Products Organization (JBPO). He also received honoraria from CSL Behring Co. Ltd. Dr. Katsuno is supported by a JSPS KAKENHI Grant Number JP20H00527, grants from the Japan Agency for Medical Research and Development (Nos. 19ek0109221, 19ek0109359, 19dk0207027, 19lk0201101, and 19dm0107155), a grant from the Naito Foundation and a grant from the Hori Sciences and Arts Foundation. He received honoraria from Takeda Pharmaceutical Co. Ltd., Alnylam Japan, Daiichi Sankyo Co. Ltd., Otsuka Pharmaceutical Co. Ltd., Novartis Pharma Co. Ltd., Biogen Japan and UCB Japan and grants from Zenyaku Kogyo Co. Ltd., Japan Blood Products Organization, Mitsubishi-Tanabe Pharma, CSL Behring Co. Ltd., Dainippon Sumitomo Pharma Co. Ltd., Otsuka Pharmaceutical Co. Ltd. and Daiichi Sankyo Co. Ltd.

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Authors and Affiliations

  1. Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Yuki Fukami, Masahiro Iijima, Haruki Koike, Shinichiro Yamada, Atsushi Hashizume & Masahisa Katsuno

  2. Division of Advanced Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8560, Japan

    Masahiro Iijima

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  1. Yuki Fukami
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Contributions

Drafting/revising the manuscript for content: YF, MI, HK, and MK. Study concept and design: YF, MI, and MK. Acquisition of samples, data, analysis and interpretation of data: YF, MI, HK, SY, AH and MK.

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Correspondence to Masahiro Iijima or Masahisa Katsuno.

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Ethics Review Committee of the Nagoya University Graduate School of Medicine, Nagoya, Japan.

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Not commissioned; externally peer reviewed.

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Cite this article

Fukami, Y., Iijima, M., Koike, H. et al. Association of serum neurofilament light chain levels with clinicopathology of chronic inflammatory demyelinating polyneuropathy, including NF155 reactive patients. J Neurol 268, 3835–3844 (2021). https://doi.org/10.1007/s00415-021-10537-2

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  • DOI: https://doi.org/10.1007/s00415-021-10537-2

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