Anti-neurofascin-155 antibody mediated a distinct phenotype of chronic inflammatory demyelinating polyradiculoneuropathy

Lijie Zhang; Yuanyuan Zhang; Runyun Li; Jiting Zhu; Aiyu Lin; Yaping Yan; Zaiqiang Zhang; Ning Wang; Guorong Xu; Ying Fu

doi:10.1007/s00415-024-12443-9

Anti-neurofascin-155 antibody mediated a distinct phenotype of chronic inflammatory demyelinating polyradiculoneuropathy

J Neurol. 2024 Aug;271(8):4991-5002. doi: 10.1007/s00415-024-12443-9. Epub 2024 May 21.

Authors

Lijie Zhang^#^{1

2}, Yuanyuan Zhang^#^{1

2}, Runyun Li^#^{1

2}, Jiting Zhu^{1

2}, Aiyu Lin^{1

2}, Yaping Yan³, Zaiqiang Zhang^{4

5}, Ning Wang^{6

7}, Guorong Xu^{8

9}, Ying Fu^{10

11}

Affiliations

¹ Department of Neurology and Institute of Neurology of First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, 350005, China.
² Department of Neurology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China.
³ Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an, 710119, China.
⁴ Department of Neurology, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China.
⁵ Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China.
⁶ Department of Neurology and Institute of Neurology of First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, 350005, China. ningwang@fjmu.edu.cn.
⁷ Department of Neurology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China. ningwang@fjmu.edu.cn.
⁸ Department of Neurology and Institute of Neurology of First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, 350005, China. guorongxu@fjmu.edu.cn.
⁹ Department of Neurology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China. guorongxu@fjmu.edu.cn.
¹⁰ Department of Neurology and Institute of Neurology of First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, 350005, China. fuying@fjmu.edu.cn.
¹¹ Department of Neurology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China. fuying@fjmu.edu.cn.

^# Contributed equally.

PMID: 38771386
DOI: 10.1007/s00415-024-12443-9

Abstract

Background: To investigate Ranvier's autoantibodies prevalence and isotypes in various peripheral neuropathy variants, compare clinical features between seronegative and seropositive patients, and elucidate immune mechanisms underlying antibody generation.

Methods: Antibodies against anti-neurofascin-155 (NF155), NF186, contactin-1 (CNTN1), CNTN2, contactin-associated protein 1 (CASPR1), and CASPR2 were identified through cell-based assays. Plasma cytokines were analyzed in anti-NF155 antibody-positive chronic inflammatory demyelinating polyneuropathy (NF155⁺ CIDP) and Ranvier's antibodies-negative CIDP (Ab^- CIDP) patients using a multiplexed fluorescent immunoassay, validated in vitro in a cell culture model.

Results: In 368 plasma samples, 50 Ranvier's autoantibodies were found in 45 individuals, primarily in CIDP cases (25 out of 69 patients) and in 10 out of 122 Guillain-Barré syndrome patients. Anti-NF155 and CNTN1-IgG were exclusive to CIDP. Fourteen samples were NF155-IgG, primarily IgG4 subclass, linked to CIDP features including early onset, tremor, sensory disturbance, elevated CSF protein, prolonged motor latency, conduction block, and poor treatment response. NF155-IgG had low sensitivity (20.28%) but high specificity (100%) for CIDP, rising to 88.88% with tremor and prolonged motor latency. Cytokine profiling in NF155⁺ CIDP revealed distinct immune responses involving helper T cells, toll-like receptor pathways. Some NF155⁺ CIDP patients had circulating NF155-specific B cells producing NF155-IgG without antigen presence, suggesting therapeutic potential.

Conclusion: The study emphasizes the high specificity and sensitivity of NF155-IgG for diagnosing CIDP characterized by distinctive features. Further investigation into circulating NF155-specific B cell phenotypes may pave the way for B cell directed therapy.

Keywords: Anti-neurofascin 155; Autoantibodies; Chronic inflammatory demyelinating polyradiculoneuropathy; Diagnostic precision; Immune mechanisms.

MeSH terms

Adult
Aged
Autoantibodies* / blood
Cell Adhesion Molecules* / blood
Cell Adhesion Molecules* / immunology
Contactin 1 / immunology
Cytokines / blood
Female
Humans
Male
Middle Aged
Nerve Growth Factors* / blood
Nerve Growth Factors* / immunology
Phenotype*
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating* / blood
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating* / diagnosis
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating* / immunology
Ranvier's Nodes / immunology

Substances

NFASC protein, human
Cell Adhesion Molecules
Nerve Growth Factors
Autoantibodies
Cytokines
Contactin 1

Abstract

MeSH terms

Substances

Grants and funding