Antibodies to neurofascin, contactin-1, and contactin-associated protein 1 in CIDP: Clinical relevance of IgG isotype.
Journal
Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
entrez:
23
11
2019
pubmed:
23
11
2019
medline:
16
2
2021
Statut:
epublish
Résumé
To assess the prevalence and isotypes of anti-nodal/paranodal antibodies to nodal/paranodal proteins in a large chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) cohort, compare clinical features in seronegative vs seropositive patients, and gather evidence of their isotype-specific pathogenic role. Antibodies to neurofascin-155 (Nfasc155), neurofascin-140/186 (Nfasc140/186), contactin-1 (CNTN1), and contactin-associated protein 1 (Caspr1) were detected with ELISA and/or cell-based assay. Antibody pathogenicity was tested by immunohistochemistry on skin biopsy, intraneural injection, and cell aggregation assay. Of 342 patients with CIDP, 19 (5.5%) had antibodies against Nfasc155 (n = 9), Nfasc140/186 and Nfasc155 (n = 1), CNTN1 (n = 3), and Caspr1 (n = 6). Antibodies were absent from healthy and disease controls, including neuropathies of different causes, and were mostly detected in patients with European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) definite CIDP (n = 18). Predominant antibody isotypes were immunoglobulin G (IgG)4 (n = 13), IgG3 (n = 2), IgG1 (n = 2), or undetectable (n = 2). IgG4 antibody-associated phenotypes included onset before 30 years, severe neuropathy, subacute onset, tremor, sensory ataxia, and poor response to intravenous immunoglobulin (IVIG). Immunosuppressive treatments, including rituximab, cyclophosphamide, and methotrexate, proved effective if started early in IVIG-resistant IgG4-seropositive cases. Five patients with an IgG1, IgG3, or undetectable isotype showed clinical features indistinguishable from seronegative patients, including good response to IVIG. IgG4 autoantibodies were associated with morphological changes at paranodes in patients' skin biopsies. We also provided preliminary evidence from a single patient about the pathogenicity of anti-Caspr1 IgG4, showing their ability to penetrate paranodal regions and disrupt the integrity of the Nfasc155/CNTN1/Caspr1 complex. Our findings confirm previous data on the tight clinico-serological correlation between antibodies to nodal/paranodal proteins and CIDP. Despite the low prevalence, testing for their presence and isotype could ultimately be part of the diagnostic workup in suspected inflammatory demyelinating neuropathy to improve diagnostic accuracy and guide treatment. This study provides Class III evidence that antibodies to nodal/paranodal proteins identify patients with CIDP (sensitivity 6%, specificity 100%).
Identifiants
pubmed: 31753915
pii: 7/1/e639
doi: 10.1212/NXI.0000000000000639
pmc: PMC6935837
pii:
doi:
Substances chimiques
Autoantibodies
0
CNTN1 protein, human
0
CNTNAP1 protein, human
0
Cell Adhesion Molecules
0
Cell Adhesion Molecules, Neuronal
0
Contactin 1
0
Immunoglobulin G
0
NFASC protein, human
0
Nerve Growth Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NINDS NIH HHS
ID : U54 NS065712
Pays : United States
Organisme : Wellcome Trust
ID : 204841/Z/16/Z
Pays : United Kingdom
Informations de copyright
Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
Références
Neuromuscul Disord. 2017 Mar;27(3):290-293
pubmed: 27986399
J Peripher Nerv Syst. 2012 Mar;17(1):62-71
pubmed: 22462667
Ann Clin Transl Neurol. 2015 Oct;2(10):960-71
pubmed: 26478896
Neurology. 2014 Mar 11;82(10):879-86
pubmed: 24523485
J Biol Chem. 2014 Mar 14;289(11):7907-18
pubmed: 24497634
Neurology. 2016 Mar 1;86(9):800-7
pubmed: 26843559
J Neuroimmunol. 2016 Dec 15;301:16-22
pubmed: 27852440
J Neurol Neurosurg Psychiatry. 2019 Feb;90(2):125-132
pubmed: 30297520
Brain. 2016 Jun;139(Pt 6):1700-12
pubmed: 27017186
Exp Neurol. 2017 Jan;287(Pt 1):84-90
pubmed: 27746185
J Neurol Neurosurg Psychiatry. 2006 Aug;77(8):973-6
pubmed: 16574730
Eur J Neurol. 2010 Jul;17(7):903-12, e44-9
pubmed: 20642627
Muscle Nerve. 2019 Mar;59(3):E19-E21
pubmed: 30488516
Neurology. 2012 Dec 4;79(23):2241-8
pubmed: 23100406
Front Neurol. 2018 Nov 27;9:997
pubmed: 30538665
Neurol Neuroimmunol Neuroinflamm. 2015 Sep 03;2(5):e149
pubmed: 26401517
Ann Neurol. 2013 Mar;73(3):370-80
pubmed: 23280477
J Neurol Neurosurg Psychiatry. 2018 Jun;89(6):627-635
pubmed: 29248893
J Clin Invest. 2019 Mar 14;129(6):2222-2236
pubmed: 30869655
Neurol Neuroimmunol Neuroinflamm. 2016 Jun 07;3(4):e238
pubmed: 27308303
J Neurol Neurosurg Psychiatry. 2017 Jun;88(6):465-473
pubmed: 28073817
J Peripher Nerv Syst. 2010 Mar;15(1):1-9
pubmed: 20433600
Brain. 2016 Oct;139(Pt 10):2617-2630
pubmed: 27474220
Brain. 2015 Jun;138(Pt 6):1484-91
pubmed: 25808373
Brain. 2017 Jul 1;140(7):1851-1858
pubmed: 28575198
J Peripher Nerv Syst. 2013 Jun;18(2):168-76
pubmed: 23781964