Download PDF
CC BY 4.0 · Arq Neuropsiquiatr 2025; 83(04): s00451805073
DOI: 10.1055/s-0045-1805073
Review Article

Immune-mediated insights into clinical and specific autoantibodies in acute and chronic immune-mediated nodo-paranodopathies

Marcus Vinícius Magno Gonçalves 
1   Universidade da Região de Joinville, Curso de Medicina, Departamento de Neurologia, Joinville SC, Brazil.
,
Pedro José Tomaselli 
2   Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Neurociências e Ciências do Comportamento, Ribeirão Preto SP, Brazil.
,
Wilson Marques Junior 
2   Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Neurociências e Ciências do Comportamento, Ribeirão Preto SP, Brazil.
3   Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Ribeirão Preto SP, Brazil.
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Abstract

The recognition of the molecular structures, namely the node of Ranvier and the axonal regions surrounding it (the paranode and juxtaparanode), as the primary target for specific autoantibodies has introduced a new site for neurological location (microtopographic structures), in contrast to the prevailing understanding, in which lesions to neural macrostructures (roots, nerves, and/or plexus) were the focus of semiologists and electrophysiologists for topographic, syndromic, and nosological diagnoses. Therefore, there was a need to understand and characterize the components of these neural microstructures that are grouped in small regions within the nerve to optimize clinical and therapeutic reasoning.

Keywords

Neuropathies - Neuritis

Authors' Contributions

All authors contributed to the conceptualization and design of the work, data acquisition, analysis and/or interpretation of data, and writing or review of the manuscript. All authors approved the final version of the manuscript and agree to be responsible for all aspects of the work.


Editor-in-Chief: Hélio A. G. Teive.


Associate Editor: Francisco Gondim.




Publication History

Received: 22 October 2024

Accepted: 26 December 2024

Article published online:
19 March 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

Thieme Revinter Publicações Ltda.
Rua Rego Freitas, 175, loja 1, República, São Paulo, SP, CEP 01220-010, Brazil

Bibliographical Record
Marcus Vinícius Magno Gonçalves, Pedro José Tomaselli, Wilson Marques Junior. Immune-mediated insights into clinical and specific autoantibodies in acute and chronic immune-mediated nodo-paranodopathies. Arq Neuropsiquiatr 2025; 83: s00451805073.
DOI: 10.1055/s-0045-1805073
 

  • References

  • 1 Van den Bergh PYK, van Doorn PA. European Academy of Neurology/Peripheral Nerve Society guideline on diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint Task Force-Second revision. J Peripher Nerv Syst 2021; 26 (03) 242-268
    CrossrefPubMedSearch in Google Scholar
  • 2 Bunschoten C, Jacobs BC, Van den Bergh PYK, Cornblath DR, van Doorn PA. Progress in diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy. Lancet Neurol 2019; 18 (08) 784-794
    CrossrefPubMedSearch in Google Scholar
  • 3 Koike H, Kadoya M, Kaida KI. et al. Paranodal dissection in chronic inflammatory demyelinating polyneuropathy with anti-neurofascin-155 and anti-contactin-1 antibodies. J Neurol Neurosurg Psychiatry 2017; 88 (06) 465-473
    CrossrefPubMedSearch in Google Scholar
  • 4 Schafer DP, Bansal R, Hedstrom KL, Pfeiffer SE, Rasband MN. Does paranode formation and maintenance require partitioning of neurofascin 155 into lipid rafts?. J Neurosci 2004; 24 (13) 3176-3185
    CrossrefPubMedSearch in Google Scholar
  • 5 Uncini A, Vallat JM. Autoimmune nodo-paranodopathies of peripheral nerve: the concept is gaining ground. J Neurol Neurosurg Psychiatry 2018; 89 (06) 627-635
    CrossrefPubMedSearch in Google Scholar
  • 6 Rinaldi S, Bennett DL. Pathogenic mechanisms in inflammatory and paraproteinaemic peripheral neuropathies. Curr Opin Neurol 2014; 27 (05) 541-551
    CrossrefPubMedSearch in Google Scholar
  • 7 Svahn J, Antoine JC, Camdessanché JP. Pathophysiology and biomarkers in chronic inflammatory demyelinating polyradiculoneuropathies. Rev Neurol (Paris) 2014; 170 (12) 808-817
    CrossrefPubMedSearch in Google Scholar
  • 8 Lonigro A, Devaux JJ. Disruption of neurofascin and gliomedin at nodes of Ranvier precedes demyelination in experimental allergic neuritis. Brain 2009; 132 (Pt 1): 260-273
    CrossrefPubMedSearch in Google Scholar
  • 9 Uncini A. Autoimmune nodo-paranodopathies 10 years later: Clinical features, pathophysiology and treatment. J Peripher Nerv Syst 2023; 28 (Suppl. 03) S23-S35
    CrossrefPubMedSearch in Google Scholar
  • 10 Becker EB, Zuliani L, Pettingill R. et al. Contactin-associated protein-2 antibodies in non-paraneoplastic cerebellar ataxia. J Neurol Neurosurg Psychiatry 2012; 83 (04) 437-440
    CrossrefPubMedSearch in Google Scholar
  • 11 Uncini A. A common mechanism and a new categorization for anti-ganglioside antibody-mediated neuropathies. Exp Neurol 2012; 235 (02) 513-516
    CrossrefPubMedSearch in Google Scholar
  • 12 Kira JI, Yamasaki R, Ogata H. Anti-neurofascin autoantibody and demyelination. Neurochem Int 2019; 130: 104360
    CrossrefPubMedSearch in Google Scholar
  • 13 Fujita A, Ogata H, Yamasaki R, Matsushita T, Kira JI. Parallel fluctuation of anti-neurofascin 155 antibody levels with clinico-electrophysiological findings in patients with chronic inflammatory demyelinating polyradiculoneuropathy. J Neurol Sci 2018; 384: 107-112
    CrossrefPubMedSearch in Google Scholar
  • 14 Ogata H, Matsuse D, Yamasaki R. et al. A nationwide survey of combined central and peripheral demyelination in Japan. J Neurol Neurosurg Psychiatry 2016; 87 (01) 29-36
    CrossrefPubMedSearch in Google Scholar
  • 15 Manso C, Querol L, Mekaouche M, Illa I, Devaux JJ. Contactin-1 IgG4 antibodies cause paranode dismantling and conduction defects. Brain 2016; 139 (Pt 6): 1700-1712
    CrossrefPubMedSearch in Google Scholar
  • 16 Kriebel M, Wuchter J, Trinks S, Volkmer H. Neurofascin: a switch between neuronal plasticity and stability. Int J Biochem Cell Biol 2012; 44 (05) 694-697
    CrossrefPubMedSearch in Google Scholar
  • 17 Hortsch M, Nagaraj K, Mualla R. The L1 family of cell adhesion molecules: a sickening number of mutations and protein functions. Adv Neurobiol 2014; 8: 195-229
    CrossrefPubMedSearch in Google Scholar
  • 18 Ogata H, Yamasaki R, Hiwatashi A. et al. Characterization of IgG4 anti-neurofascin 155 antibody-positive polyneuropathy. Ann Clin Transl Neurol 2015; 2 (10) 960-971
    CrossrefPubMedSearch in Google Scholar
  • 19 Devaux JJ, Miura Y, Fukami Y. et al. Neurofascin-155 IgG4 in chronic inflammatory demyelinating polyneuropathy. Neurology 2016; 86 (09) 800-807
    CrossrefPubMedSearch in Google Scholar
  • 20 Martinez-Martinez L, Lleixà MC, Boera-Carnicero G. et al. Anti-NF155 chronic inflammatory demyelinating polyradiculoneuropathy strongly associates to HLA-DRB15. J Neuroinflammation 2017; 14 (01) 224
    CrossrefPubMedSearch in Google Scholar
  • 21 Bailly L, Mongin M, Delorme C. et al. Tremor Associated with Chronic Inflammatory Demyelinating Polyneuropathy and Anti-Neurofascin-155 Antibodies. Tremor Other Hyperkinet Mov (N Y) 2018; 8: 606
    CrossrefPubMedSearch in Google Scholar
  • 22 Garg N, Park SB, Yiannikas C. et al. Neurofascin-155 IGG4 Neuropathy: Pathophysiological Insights, Spectrum of Clinical Severity and Response To treatment. Muscle Nerve 2018; 57 (05) 848-851
    CrossrefPubMedSearch in Google Scholar
  • 23 Shimizu M, Koda T, Nakatsuji Y, Ogata H, Kira JI, Mochizuki H. [A case of anti-neurofascin 155 antibody-positive combined central and peripheral demyelination successfully treated with plasma exchange]. Rinsho Shinkeigaku 2017; 57 (01) 41-44
    CrossrefPubMedSearch in Google Scholar
  • 24 Tajima Y, Matsumura M, Yaguchi H, Mito Y. Possible Combined Central and Peripheral Demyelination Presenting as Optic Neuritis, Cervical Myelitis, and Demyelinating Polyneuropathy with Marked Nerve Hypertrophy. Intern Med 2018; 57 (06) 867-871
    CrossrefPubMedSearch in Google Scholar
  • 25 Stich O, Perera S, Berger B. et al. Prevalence of neurofascin-155 antibodies in patients with multiple sclerosis. J Neurol Sci 2016; 364: 29-32
    CrossrefPubMedSearch in Google Scholar
  • 26 Querol L, Siles AM, Alba-Rovira R. et al. Antibodies against peripheral nerve antigens in chronic inflammatory demyelinating polyradiculoneuropathy. Sci Rep 2017; 7 (01) 14411 . ISSN 2045-2322.
    CrossrefPubMedSearch in Google Scholar
  • 27 Kawamura N, Yamasaki R, Yonekawa T. et al. Anti-neurofascin antibody in patients with combined central and peripheral demyelination. Neurology 2013; 81 (08) 714-722
    CrossrefPubMedSearch in Google Scholar
  • 28 Miura Y, Devaux JJ, Fukami Y. et al; CNTN1-CIDP Study Group. Contactin 1 IgG4 associates to chronic inflammatory demyelinating polyneuropathy with sensory ataxia. Brain 2015; 138 (Pt 6): 1484-1491
    CrossrefPubMedSearch in Google Scholar
  • 29 Kuwabara S, Misawa S, Mori M. Nodopathy: chronic inflammatory demyelinating polyneuropathy with anti-neurofascin 155 antibodies. J Neurol Neurosurg Psychiatry 2017; 88 (06) 459
    CrossrefPubMedSearch in Google Scholar
  • 30 Illa I. ARTHUR ASBURY LECTURE: Chronic inflammatory demyelinating polyradiculoneuropathy: clinical aspects and new animal models of auto-immunity to nodal components. J Peripher Nerv Syst 2017; 22 (04) 418-424
    CrossrefPubMedSearch in Google Scholar
  • 31 Doppler K, Appeltshauser L, Villmann C. et al. Auto-antibodies to contactin-associated protein 1 (Caspr) in two patients with painful inflammatory neuropathy. Brain 2016; 139 (Pt 10): 2617-2630
    CrossrefPubMedSearch in Google Scholar
  • 32 Querol L, Illa I. Paranodal and other autoantibodies in chronic inflammatory neuropathies. Curr Opin Neurol 2015; 28 (05) 474-479
    CrossrefPubMedSearch in Google Scholar
  • 33 Briani C, Salvalaggio A, Ruiz M. et al. Tongue tremor in neurofascin-155 IgG4 seropositive chronic inflammatory polyradiculoneuropathy. J Neuroimmunol 2019; 330: 178-180
    CrossrefPubMedSearch in Google Scholar
  • 34 Pascual-Goñi E, Martín-Aguilar L, Querol L. Autoantibodies in chronic inflammatory demyelinating polyradiculoneuropathy. Curr Opin Neurol 2019; 32 (05) 651-657
    CrossrefPubMedSearch in Google Scholar
  • 35 Broers MC, Bunschoten C, Nieboer D, Lingsma HF, Jacobs BC. Incidence and Prevalence of Chronic Inflammatory Demyelinating Polyradiculoneuropathy: A Systematic Review and Meta-Analysis. Neuroepidemiology 2019; 52 (3-4): 161-172
    CrossrefPubMedSearch in Google Scholar
  • 36 Ikeda S, Koike H, Nishi R. et al. Clinicopathological characteristics of subtypes of chronic inflammatory demyelinating polyradiculoneuropathy. J Neurol Neurosurg Psychiatry 2019; 90 (09) 988-996
    CrossrefPubMedSearch in Google Scholar
  • 37 Aktas O. Shifting borders, crossing boundaries: The case of combined central and peripheral demyelination. Mult Scler 2018; 24 (04) 550-551
    CrossrefPubMedSearch in Google Scholar