Neurofascin and Compact Myelin Antigen-Specific T Cell Response Pattern in Chronic Inflammatory Demyelinating Polyneuropathy Subtypes

ObjectiveThe objective of this study is to investigate whether chronic inflammatory demyelinating polyneuropathy (CIDP) and its subtypes differ in their type 1 T-helper (TH1) cell response against nodal/paranodal neurofascin (NF186, NF155) as well as myelin protein zero (P0 180–199) and myelin basic...

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Main Authors: Jan-Markus Diederich, Maximilian Staudt, Christian Meisel, Katrin Hahn, Edgar Meinl, Andreas Meisel, Juliane Klehmet
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-03-01
Series:Frontiers in Neurology
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fneur.2018.00171/full
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author Jan-Markus Diederich
Maximilian Staudt
Christian Meisel
Katrin Hahn
Edgar Meinl
Andreas Meisel
Andreas Meisel
Juliane Klehmet
author_facet Jan-Markus Diederich
Maximilian Staudt
Christian Meisel
Katrin Hahn
Edgar Meinl
Andreas Meisel
Andreas Meisel
Juliane Klehmet
author_sort Jan-Markus Diederich
collection DOAJ
description ObjectiveThe objective of this study is to investigate whether chronic inflammatory demyelinating polyneuropathy (CIDP) and its subtypes differ in their type 1 T-helper (TH1) cell response against nodal/paranodal neurofascin (NF186, NF155) as well as myelin protein zero (P0 180–199) and myelin basic protein (MBP 82–100).MethodsInterferon-gamma (IFN-γ) enzyme-linked immunospot assay was used to detect antigen-specific T cell responses in 48 patients suffering typical CIDP (n = 18), distal acquired demyelinating polyneuropathy (n = 8), multifocal acquired demyelinating sensory and motor polyneuropathy (MADSAM; n = 9), and sensory CIDP (n = 13) compared to other non-immune polyneuropathy (ON; n = 19) and healthy controls (n = 9).ResultsCompared to controls, MADSAM and sensory CIDP patients showed broadest IFN-γ T cell responses to all four antigens. Positive IFN-γ responses against two or more antigens were highly predictive for CIDP (positive predictive value = 0.95) and were found in 77% of CIDP patients. Patients with limited antigen-specific response were females, more severely affected with neuropathic pain and proximal paresis. The area under the receiver operating characteristics curve (AUC) of NF186 in MADSAM was 0.94 [95% confidential interval (CI) 0.82–1.00] compared to ON. For sensory CIDP, AUC of P0 180–199 was 0.94 (95% CI 0.86–1.00) and for MBP 82–100 0.95 (95% CI 0.88–1.00) compared to ON.ConclusionCell-mediated immune responses to (para)nodal and myelin-derived antigens are common in CIDP. TH1 response against NF186 may be used as a biomarker for MADSAM and TH1 responses against P0 180–199 and MBP 82–100 as biomarkers for sensory CIDP. Larger multicenter studies study are warranted in order to establish these immunological markers as a diagnostic tools.
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spelling doaj.art-70fb4453e4f74bcc84682ec5a4e361c52022-12-21T22:46:40ZengFrontiers Media S.A.Frontiers in Neurology1664-22952018-03-01910.3389/fneur.2018.00171354983Neurofascin and Compact Myelin Antigen-Specific T Cell Response Pattern in Chronic Inflammatory Demyelinating Polyneuropathy SubtypesJan-Markus Diederich0Maximilian Staudt1Christian Meisel2Katrin Hahn3Edgar Meinl4Andreas Meisel5Andreas Meisel6Juliane Klehmet7Neurocure Research Center Berlin, Charité University Medicine, Berlin, GermanyNeurocure Research Center Berlin, Charité University Medicine, Berlin, GermanyDepartment of Medical Immunology, Charité University Medicine, Berlin, GermanyDepartment of Neurology, Charité University Medicine, Berlin, GermanyClinical Neuroimmunology, Ludwigs-Maximilians University, Munich, GermanyNeurocure Research Center Berlin, Charité University Medicine, Berlin, GermanyDepartment of Neurology, Charité University Medicine, Berlin, GermanyNeurocure Research Center Berlin, Charité University Medicine, Berlin, GermanyObjectiveThe objective of this study is to investigate whether chronic inflammatory demyelinating polyneuropathy (CIDP) and its subtypes differ in their type 1 T-helper (TH1) cell response against nodal/paranodal neurofascin (NF186, NF155) as well as myelin protein zero (P0 180–199) and myelin basic protein (MBP 82–100).MethodsInterferon-gamma (IFN-γ) enzyme-linked immunospot assay was used to detect antigen-specific T cell responses in 48 patients suffering typical CIDP (n = 18), distal acquired demyelinating polyneuropathy (n = 8), multifocal acquired demyelinating sensory and motor polyneuropathy (MADSAM; n = 9), and sensory CIDP (n = 13) compared to other non-immune polyneuropathy (ON; n = 19) and healthy controls (n = 9).ResultsCompared to controls, MADSAM and sensory CIDP patients showed broadest IFN-γ T cell responses to all four antigens. Positive IFN-γ responses against two or more antigens were highly predictive for CIDP (positive predictive value = 0.95) and were found in 77% of CIDP patients. Patients with limited antigen-specific response were females, more severely affected with neuropathic pain and proximal paresis. The area under the receiver operating characteristics curve (AUC) of NF186 in MADSAM was 0.94 [95% confidential interval (CI) 0.82–1.00] compared to ON. For sensory CIDP, AUC of P0 180–199 was 0.94 (95% CI 0.86–1.00) and for MBP 82–100 0.95 (95% CI 0.88–1.00) compared to ON.ConclusionCell-mediated immune responses to (para)nodal and myelin-derived antigens are common in CIDP. TH1 response against NF186 may be used as a biomarker for MADSAM and TH1 responses against P0 180–199 and MBP 82–100 as biomarkers for sensory CIDP. Larger multicenter studies study are warranted in order to establish these immunological markers as a diagnostic tools.http://journal.frontiersin.org/article/10.3389/fneur.2018.00171/fullchronic inflammatory demyelinating polyneuropathyneurofascinmyelin basic proteinmyelin protein zeroT cell responsechronic inflammatory demyelinating polyneuropathy subtypes
spellingShingle Jan-Markus Diederich
Maximilian Staudt
Christian Meisel
Katrin Hahn
Edgar Meinl
Andreas Meisel
Andreas Meisel
Juliane Klehmet
Neurofascin and Compact Myelin Antigen-Specific T Cell Response Pattern in Chronic Inflammatory Demyelinating Polyneuropathy Subtypes
Frontiers in Neurology
chronic inflammatory demyelinating polyneuropathy
neurofascin
myelin basic protein
myelin protein zero
T cell response
chronic inflammatory demyelinating polyneuropathy subtypes
title Neurofascin and Compact Myelin Antigen-Specific T Cell Response Pattern in Chronic Inflammatory Demyelinating Polyneuropathy Subtypes
title_full Neurofascin and Compact Myelin Antigen-Specific T Cell Response Pattern in Chronic Inflammatory Demyelinating Polyneuropathy Subtypes
title_fullStr Neurofascin and Compact Myelin Antigen-Specific T Cell Response Pattern in Chronic Inflammatory Demyelinating Polyneuropathy Subtypes
title_full_unstemmed Neurofascin and Compact Myelin Antigen-Specific T Cell Response Pattern in Chronic Inflammatory Demyelinating Polyneuropathy Subtypes
title_short Neurofascin and Compact Myelin Antigen-Specific T Cell Response Pattern in Chronic Inflammatory Demyelinating Polyneuropathy Subtypes
title_sort neurofascin and compact myelin antigen specific t cell response pattern in chronic inflammatory demyelinating polyneuropathy subtypes
topic chronic inflammatory demyelinating polyneuropathy
neurofascin
myelin basic protein
myelin protein zero
T cell response
chronic inflammatory demyelinating polyneuropathy subtypes
url http://journal.frontiersin.org/article/10.3389/fneur.2018.00171/full
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