Evidence map›Paper›PMID 35948442›Full record

ArticleNeurology(R) neuroimmunology & neuroinflammation2022

IgG4 Valency Modulates the Pathogenicity of Anti-Neurofascin-155 IgG4 in Autoimmune Nodopathy.

Alexandre Jentzer, Arthur Attal, Clémence Roué, Julie Raymond, Cinta Lleixà, Isabel Illa, Luis Querol, Guillaume Taieb, Jérôme Devaux, anti–neurofascin-155 study group

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In one paragraph

Article in Neurology(R) neuroimmunology & neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.6field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Antibody-Mediated Nodo- and Paranodopathies.Journal of clinical medicine · 2024
    Review
  6. Review
  7. Review
  8. Article
  9. Article
  10. Neurology(R) neuroimmunology & neuroinflammation · 2023
    Article
  11. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 7 institutions in 2 countries.

Alexandre JentzerFrom the Institute for Neurosciences of Montpellier (A.J., A.A., G.T., J.D.), INSERM U1051, Montpellier University, Hôpital Saint Eloi, France; Department of Immunology (A.J.), CHU Montpellier, France ; Department of Neurology (A.A., G.T.), CHU Montpellier, Hôpital Gui de Chauliac, France; Institut de Génomique Fonctionnelle (C.R., J.R., G.T., J.D.), CNRS UMR5203, France; and Neuromuscular Diseases Unit (C.L., I.I., L.Q.), Hospital de la Santa Creu i Sant Pau, Universitat Autónoma de Barcelona, Spain.
Arthur AttalFrom the Institute for Neurosciences of Montpellier (A.J., A.A., G.T., J.D.), INSERM U1051, Montpellier University, Hôpital Saint Eloi, France; Department of Immunology (A.J.), CHU Montpellier, France ; Department of Neurology (A.A., G.T.), CHU Montpellier, Hôpital Gui de Chauliac, France; Institut de Génomique Fonctionnelle (C.R., J.R., G.T., J.D.), CNRS UMR5203, France; and Neuromuscular Diseases Unit (C.L., I.I., L.Q.), Hospital de la Santa Creu i Sant Pau, Universitat Autónoma de Barcelona, Spain.
Clémence RouéFrom the Institute for Neurosciences of Montpellier (A.J., A.A., G.T., J.D.), INSERM U1051, Montpellier University, Hôpital Saint Eloi, France; Department of Immunology (A.J.), CHU Montpellier, France ; Department of Neurology (A.A., G.T.), CHU Montpellier, Hôpital Gui de Chauliac, France; Institut de Génomique Fonctionnelle (C.R., J.R., G.T., J.D.), CNRS UMR5203, France; and Neuromuscular Diseases Unit (C.L., I.I., L.Q.), Hospital de la Santa Creu i Sant Pau, Universitat Autónoma de Barcelona, Spain.
Julie RaymondFrom the Institute for Neurosciences of Montpellier (A.J., A.A., G.T., J.D.), INSERM U1051, Montpellier University, Hôpital Saint Eloi, France; Department of Immunology (A.J.), CHU Montpellier, France ; Department of Neurology (A.A., G.T.), CHU Montpellier, Hôpital Gui de Chauliac, France; Institut de Génomique Fonctionnelle (C.R., J.R., G.T., J.D.), CNRS UMR5203, France; and Neuromuscular Diseases Unit (C.L., I.I., L.Q.), Hospital de la Santa Creu i Sant Pau, Universitat Autónoma de Barcelona, Spain.
Cinta LleixàFrom the Institute for Neurosciences of Montpellier (A.J., A.A., G.T., J.D.), INSERM U1051, Montpellier University, Hôpital Saint Eloi, France; Department of Immunology (A.J.), CHU Montpellier, France ; Department of Neurology (A.A., G.T.), CHU Montpellier, Hôpital Gui de Chauliac, France; Institut de Génomique Fonctionnelle (C.R., J.R., G.T., J.D.), CNRS UMR5203, France; and Neuromuscular Diseases Unit (C.L., I.I., L.Q.), Hospital de la Santa Creu i Sant Pau, Universitat Autónoma de Barcelona, Spain.
Isabel IllaFrom the Institute for Neurosciences of Montpellier (A.J., A.A., G.T., J.D.), INSERM U1051, Montpellier University, Hôpital Saint Eloi, France; Department of Immunology (A.J.), CHU Montpellier, France ; Department of Neurology (A.A., G.T.), CHU Montpellier, Hôpital Gui de Chauliac, France; Institut de Génomique Fonctionnelle (C.R., J.R., G.T., J.D.), CNRS UMR5203, France; and Neuromuscular Diseases Unit (C.L., I.I., L.Q.), Hospital de la Santa Creu i Sant Pau, Universitat Autónoma de Barcelona, Spain.
Luis QuerolFrom the Institute for Neurosciences of Montpellier (A.J., A.A., G.T., J.D.), INSERM U1051, Montpellier University, Hôpital Saint Eloi, France; Department of Immunology (A.J.), CHU Montpellier, France ; Department of Neurology (A.A., G.T.), CHU Montpellier, Hôpital Gui de Chauliac, France; Institut de Génomique Fonctionnelle (C.R., J.R., G.T., J.D.), CNRS UMR5203, France; and Neuromuscular Diseases Unit (C.L., I.I., L.Q.), Hospital de la Santa Creu i Sant Pau, Universitat Autónoma de Barcelona, Spain.
Guillaume TaiebFrom the Institute for Neurosciences of Montpellier (A.J., A.A., G.T., J.D.), INSERM U1051, Montpellier University, Hôpital Saint Eloi, France; Department of Immunology (A.J.), CHU Montpellier, France ; Department of Neurology (A.A., G.T.), CHU Montpellier, Hôpital Gui de Chauliac, France; Institut de Génomique Fonctionnelle (C.R., J.R., G.T., J.D.), CNRS UMR5203, France; and Neuromuscular Diseases Unit (C.L., I.I., L.Q.), Hospital de la Santa Creu i Sant Pau, Universitat Autónoma de Barcelona, Spain.
Jérôme DevauxFrom the Institute for Neurosciences of Montpellier (A.J., A.A., G.T., J.D.), INSERM U1051, Montpellier University, Hôpital Saint Eloi, France; Department of Immunology (A.J.), CHU Montpellier, France ; Department of Neurology (A.A., G.T.), CHU Montpellier, Hôpital Gui de Chauliac, France; Institut de Génomique Fonctionnelle (C.R., J.R., G.T., J.D.), CNRS UMR5203, France; and Neuromuscular Diseases Unit (C.L., I.I., L.Q.), Hospital de la Santa Creu i Sant Pau, Universitat Autónoma de Barcelona, Spain. jerome.devaux@inserm.fr.
anti–neurofascin-155 study group
Hôpital Saint Eloi · FRUniversitat Autònoma de Barcelona · ESCentre Hospitalier Universitaire de Montpellier · FRCentre National de la Recherche Scientifique · FRHospital de Sant Pau · ESInstitut de Génomique Fonctionnelle · FRInstitute for Neurosciences of Montpellier · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesIgG4 autoantibodies to neurofascin-155 (Nfasc155) are associated with a subgroup of patients with chronic inflammatory demyelinating polyneuropathy (CIDP), currently named autoimmune nodopathy. We previously demonstrated that those antibodies alter conduction along myelinated axons by inducing Nfasc155 depletion and paranode destruction. In blood, IgG4 have the potency to exchange their moiety with other unrelated IgG4 through a process called Fab-arm exchange (FAE). This process results in functionally monovalent antibodies and may affect the pathogenicity of autoantibodies. Here, we examined this issue and whether FAE is beneficial or detrimental for Nfasc155 autoimmune nodopathy.

methodsThe bivalency and monospecificity of anti-Nfasc155 were examined by sandwich ELISA in 10 reactive patients, 10 unreactive CIDP patients, and 10 healthy controls. FAE was induced in vitro using reduced glutathione and unreactive IgG4, and the ratio of the κ:λ light chain was monitored. To determine the pathogenic potential of bivalent anti-Nfasc155 IgG4, autoantibodies derived from patients were enzymatically cleaved into monovalent Fab and bivalent F(ab')

resultsMonospecific bivalent IgG4 against Nfasc155 were detected in the serum of all reactive patients, indicating that a fraction of IgG4 have not undergone FAE in situ. These IgG4 were, nonetheless, capable of engaging into FAE with unreactive IgG4 in vitro, and this decreased the levels of monospecific antibodies and modulated the ratio of the κ:λ light chain. When injected in animals, monovalent anti-Nfasc155 Fab did not alter the formation of paranodes; by contrast, both native anti-Nfasc155 IgG4 and F(ab') DISCUSSION: Our findings demonstrate that monospecific and bivalent anti-Nfasc155 IgG4 are detected in patients and that those autoantibodies are the pathogenic ones. The transformation of anti-Nfasc155 IgG4 into monovalent Fab or functionally monovalent IgG4 through FAE strongly decreases paranodal alterations. Bivalency thus appears crucial for Nfasc155 clustering and paranode destruction.

Indexed as

Polyradiculoneuropathy, Chronic Inflammatory DemyelinatingAnimalsAutoantibodiesCell Adhesion MoleculesImmunoglobulin GNerve Growth FactorsVirulenceAutoantibodiesCell Adhesion MoleculesImmunoglobulin GNerve Growth Factors

Identifiers

PMID35948442
PMCPMC9365386
OpenAlexW4291020135

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.