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Neurofascin-155 Immunoglobulin Subtypes: Clinicopathologic Associations and Neurologic Outcomes

BACKGROUND AND OBJECTIVE: Multiple studies highlighting the diagnostic utility of neurofascin-155 (NF155)–immunoglobulin G4 (IgG4) in chronic demyelinating inflammatory polyradiculoneuropathy (CIDP) have been published. However, few studies comprehensively address the long-term outcomes or clinical...

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Autores principales: Shelly, Shahar, Klein, Christopher J., Dyck, P. James B., Paul, Pritikanta, Mauermann, Michelle L., Berini, Sarah E., Howe, Benjamin, Fryer, James P., Basal, Eati, Bakri, Hammami M., Laughlin, Ruple S., McKeon, Andrew, Pittock, Sean J., Mills, John, Dubey, Divyanshu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8673722/
https://www.ncbi.nlm.nih.gov/pubmed/34635556
http://dx.doi.org/10.1212/WNL.0000000000012932
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author Shelly, Shahar
Klein, Christopher J.
Dyck, P. James B.
Paul, Pritikanta
Mauermann, Michelle L.
Berini, Sarah E.
Howe, Benjamin
Fryer, James P.
Basal, Eati
Bakri, Hammami M.
Laughlin, Ruple S.
McKeon, Andrew
Pittock, Sean J.
Mills, John
Dubey, Divyanshu
author_facet Shelly, Shahar
Klein, Christopher J.
Dyck, P. James B.
Paul, Pritikanta
Mauermann, Michelle L.
Berini, Sarah E.
Howe, Benjamin
Fryer, James P.
Basal, Eati
Bakri, Hammami M.
Laughlin, Ruple S.
McKeon, Andrew
Pittock, Sean J.
Mills, John
Dubey, Divyanshu
author_sort Shelly, Shahar
collection PubMed
description BACKGROUND AND OBJECTIVE: Multiple studies highlighting the diagnostic utility of neurofascin-155 (NF155)–immunoglobulin G4 (IgG4) in chronic demyelinating inflammatory polyradiculoneuropathy (CIDP) have been published. However, few studies comprehensively address the long-term outcomes or clinical utility of NF155–immunoglobulin M (IgM) or NF155–immunoglobulin G (IgG) in the absence of NF155-IgG4. We evaluated phenotypic and histopathologic specificity and differences in outcomes between these NF155 antibody isotypes or IgG subclasses. We also compare NF155-IgG4-seropositive cases to other seropositive demyelinating neuropathies. METHODS: Neuropathy patient sera at Mayo Clinic were tested for NF155-IgG4, NF155-IgG, and NF155-IgM autoantibodies. Demographic and clinical data of all seropositive cases were reviewed. RESULTS: We identified 32 NF155 cases (25 NF155-IgG-positive [20 NF155-IgG4-positive], 7 NF155-IgM-seropositive). NF155-IgG4-seropositive patients clinically presented with distal more than proximal muscle weakness, positive sensory symptoms (prickling, asymmetric paresthesia, neuropathic pain), and gait ataxia. Cranial nerve involvement (11/20 [55%]) and papilledema (4/12 [33%]) occurred in many. Electrodiagnostic testing (EDX) demonstrated demyelinating polyradiculoneuropathy (19/20 [95%]). Autonomic involvement occurred in 45% (n = 9, median composite autonomic scoring scale score 3.5, range 1–7). Nerve biopsies from the NF155-IgG4 patients (n = 11) demonstrated grouped segmental demyelination (50%), myelin reduplication (45%), and paranodal swellings (50%). Most patients needed second- and third-line immunosuppression but had favorable long-term outcomes (n = 18). Among 14 patients with serial EDX over 2 years, all except one demonstrated improvement after treatment. NF155-IgG-positive, NF155-IgG4-negative (NF155-IgG-positive) and NF155-IgM-positive patients were phenotypically different from NF155-IgG4-seropositive patients. Sensory ataxia, neuropathic pain, cerebellar dysfunction, and root/plexus MRI abnormalities were significantly more common in NF155-IgG4-positive compared to myelin-associated glycoprotein (MAG)–IgM neuropathy. Chronic immune sensory polyradiculopathy (CISP)/CISP-plus phenotype was more common among contactin-1 neuropathies compared to NF155-IgG4-positive cases. NF155-IgG4-positive cases responded favorably to immunotherapy compared to MAG-IgM-seropositive cases with distal acquired demyelinating symmetric neuropathy (p < 0.001) and had better long-term clinical outcomes compared to contactin-1 IgG (p = 0.04). DISCUSSION: We report long-term follow-up and clinical outcome of NF155-IgG4 cases. NF155-IgG4 but not IgM or IgG cases have unique clinical–electrodiagnostic signature. We demonstrate NF155-IgG4-positive patients, unlike classical CIDP with neuropathic pain and dysautonomia common at presentation. Long-term outcomes were favorable. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that NF155-IgG4-seropositive patients, compared to patients with typical CIDP, present with distal more than proximal muscle weakness, positive sensory symptoms, and gait ataxia.
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spelling pubmed-86737222021-12-16 Neurofascin-155 Immunoglobulin Subtypes: Clinicopathologic Associations and Neurologic Outcomes Shelly, Shahar Klein, Christopher J. Dyck, P. James B. Paul, Pritikanta Mauermann, Michelle L. Berini, Sarah E. Howe, Benjamin Fryer, James P. Basal, Eati Bakri, Hammami M. Laughlin, Ruple S. McKeon, Andrew Pittock, Sean J. Mills, John Dubey, Divyanshu Neurology Research Article BACKGROUND AND OBJECTIVE: Multiple studies highlighting the diagnostic utility of neurofascin-155 (NF155)–immunoglobulin G4 (IgG4) in chronic demyelinating inflammatory polyradiculoneuropathy (CIDP) have been published. However, few studies comprehensively address the long-term outcomes or clinical utility of NF155–immunoglobulin M (IgM) or NF155–immunoglobulin G (IgG) in the absence of NF155-IgG4. We evaluated phenotypic and histopathologic specificity and differences in outcomes between these NF155 antibody isotypes or IgG subclasses. We also compare NF155-IgG4-seropositive cases to other seropositive demyelinating neuropathies. METHODS: Neuropathy patient sera at Mayo Clinic were tested for NF155-IgG4, NF155-IgG, and NF155-IgM autoantibodies. Demographic and clinical data of all seropositive cases were reviewed. RESULTS: We identified 32 NF155 cases (25 NF155-IgG-positive [20 NF155-IgG4-positive], 7 NF155-IgM-seropositive). NF155-IgG4-seropositive patients clinically presented with distal more than proximal muscle weakness, positive sensory symptoms (prickling, asymmetric paresthesia, neuropathic pain), and gait ataxia. Cranial nerve involvement (11/20 [55%]) and papilledema (4/12 [33%]) occurred in many. Electrodiagnostic testing (EDX) demonstrated demyelinating polyradiculoneuropathy (19/20 [95%]). Autonomic involvement occurred in 45% (n = 9, median composite autonomic scoring scale score 3.5, range 1–7). Nerve biopsies from the NF155-IgG4 patients (n = 11) demonstrated grouped segmental demyelination (50%), myelin reduplication (45%), and paranodal swellings (50%). Most patients needed second- and third-line immunosuppression but had favorable long-term outcomes (n = 18). Among 14 patients with serial EDX over 2 years, all except one demonstrated improvement after treatment. NF155-IgG-positive, NF155-IgG4-negative (NF155-IgG-positive) and NF155-IgM-positive patients were phenotypically different from NF155-IgG4-seropositive patients. Sensory ataxia, neuropathic pain, cerebellar dysfunction, and root/plexus MRI abnormalities were significantly more common in NF155-IgG4-positive compared to myelin-associated glycoprotein (MAG)–IgM neuropathy. Chronic immune sensory polyradiculopathy (CISP)/CISP-plus phenotype was more common among contactin-1 neuropathies compared to NF155-IgG4-positive cases. NF155-IgG4-positive cases responded favorably to immunotherapy compared to MAG-IgM-seropositive cases with distal acquired demyelinating symmetric neuropathy (p < 0.001) and had better long-term clinical outcomes compared to contactin-1 IgG (p = 0.04). DISCUSSION: We report long-term follow-up and clinical outcome of NF155-IgG4 cases. NF155-IgG4 but not IgM or IgG cases have unique clinical–electrodiagnostic signature. We demonstrate NF155-IgG4-positive patients, unlike classical CIDP with neuropathic pain and dysautonomia common at presentation. Long-term outcomes were favorable. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that NF155-IgG4-seropositive patients, compared to patients with typical CIDP, present with distal more than proximal muscle weakness, positive sensory symptoms, and gait ataxia. Lippincott Williams & Wilkins 2021-12-14 /pmc/articles/PMC8673722/ /pubmed/34635556 http://dx.doi.org/10.1212/WNL.0000000000012932 Text en Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Research Article
Shelly, Shahar
Klein, Christopher J.
Dyck, P. James B.
Paul, Pritikanta
Mauermann, Michelle L.
Berini, Sarah E.
Howe, Benjamin
Fryer, James P.
Basal, Eati
Bakri, Hammami M.
Laughlin, Ruple S.
McKeon, Andrew
Pittock, Sean J.
Mills, John
Dubey, Divyanshu
Neurofascin-155 Immunoglobulin Subtypes: Clinicopathologic Associations and Neurologic Outcomes
title Neurofascin-155 Immunoglobulin Subtypes: Clinicopathologic Associations and Neurologic Outcomes
title_full Neurofascin-155 Immunoglobulin Subtypes: Clinicopathologic Associations and Neurologic Outcomes
title_fullStr Neurofascin-155 Immunoglobulin Subtypes: Clinicopathologic Associations and Neurologic Outcomes
title_full_unstemmed Neurofascin-155 Immunoglobulin Subtypes: Clinicopathologic Associations and Neurologic Outcomes
title_short Neurofascin-155 Immunoglobulin Subtypes: Clinicopathologic Associations and Neurologic Outcomes
title_sort neurofascin-155 immunoglobulin subtypes: clinicopathologic associations and neurologic outcomes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8673722/
https://www.ncbi.nlm.nih.gov/pubmed/34635556
http://dx.doi.org/10.1212/WNL.0000000000012932
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