MOG-IgG in NMO and related disorders: A multicenter study of 50 patients. Part 1: Frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin

Sven Jarius, Klemens Ruprecht, Ingo Kleiter, Nadja Borisow, Nasrin Asgari, Kalliopi Pitarokoili, Florence Pache, Oliver Stich, Lena Alexandra Beume, Martin W. Hümmert, Corinna Trebst, Marius Ringelstein, Orhan Aktas, Alexander Winkelmann, Mathias Buttmann, Alexander Schwarz, Hanna Zimmermann, Alexander U. Brandt, Diego Franciotta, Marco CapobiancoJoseph Kuchling, Jürgen Haas, Mirjam Korporal-Kuhnke, Soeren Thue Lillevang, Kai Fechner, Kathrin Schanda, Friedemann Paul, Brigitte Wildemann, Markus Reindl, in cooperation with the Neuromyelitis Optica Study Group (NEMOS)

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

Background: Antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) have been suggested to play a role in a subset of patients with neuromyelitis optica and related disorders. Objective: To assess (i) the frequency of MOG-IgG in a large and predominantly Caucasian cohort of patients with optic neuritis (ON) and/or myelitis; (ii) the frequency of MOG-IgG among AQP4-IgG-positive patients and vice versa; (iii) the origin and frequency of MOG-IgG in the cerebrospinal fluid (CSF); (iv) the presence of MOG-IgG at disease onset; and (v) the influence of disease activity and treatment status on MOG-IgG titers. Methods: 614 serum samples from patients with ON and/or myelitis and from controls, including 92 follow-up samples from 55 subjects, and 18 CSF samples were tested for MOG-IgG using a live cell-based assay (CBA) employing full-length human MOG-transfected HEK293A cells. Results: MOG-IgG was detected in 95 sera from 50 patients with ON and/or myelitis, including 22/54 (40.7 %) patients with a history of both ON and myelitis, 22/103 (21.4 %) with a history of ON but no myelitis and 6/45 (13.3 %) with a history of longitudinally extensive transverse myelitis but no ON, and in 1 control patient with encephalitis and a connective tissue disorder, all of whom were negative for AQP4-IgG. MOG-IgG was absent in 221 further controls, including 83 patients with AQP4-IgG-seropositive neuromyelitis optica spectrum disorders and 85 with multiple sclerosis (MS). MOG-IgG was found in 12/18 (67 %) CSF samples from MOG-IgG-seropositive patients; the MOG-IgG-specific antibody index was negative in all cases, indicating a predominantly peripheral origin of CSF MOG-IgG. Serum and CSF MOG-IgG belonged to the complement-activating IgG1 subclass. MOG-IgG was present already at disease onset. The antibodies remained detectable in 40/45 (89 %) follow-up samples obtained over a median period of 16.5 months (range 0-123). Serum titers were higher during attacks than during remission (p < 0.0001), highest during attacks of simultaneous myelitis and ON, lowest during acute isolated ON, and declined following treatment. Conclusions: To date, this is the largest cohort studied for IgG to human full-length MOG by means of an up-to-date CBA. MOG-IgG is present in a substantial subset of patients with ON and/or myelitis, but not in classical MS. Co-existence of MOG-IgG and AQP4-IgG is highly uncommon. CSF MOG-IgG is of extrathecal origin. Serum MOG-IgG is present already at disease onset and remains detectable in the long-term course. Serum titers depend on disease activity and treatment status.

Original languageEnglish
Article number279
JournalJournal of Neuroinflammation
Volume13
Issue number1
DOIs
Publication statusPublished - Sep 26 2016

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Multicenter Studies
Immunoglobulin G
Optic Neuritis
Myelitis
Cerebrospinal Fluid
Serum
Neuromyelitis Optica
Multiple Sclerosis
Antibodies
Myelin-Oligodendrocyte Glycoprotein
Transverse Myelitis

Keywords

  • Antibody index
  • Aquaporin-4 antibodies (AQP4-IgG)
  • Autoantibodies
  • Cell-based assays
  • Cerebrospinal fluid
  • Devic's syndrome
  • Longitudinally extensive transverse myelitis (LETM)
  • Multiple sclerosis
  • Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG)
  • Neuromyelitis optica (NMO)
  • Neuromyelitis optica antibodies (NMO-IgG)
  • Neuromyelitis optica spectrum disorders (NMOSD)
  • Optic neuritis
  • Transverse Myelitis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

MOG-IgG in NMO and related disorders : A multicenter study of 50 patients. Part 1: Frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin. / Jarius, Sven; Ruprecht, Klemens; Kleiter, Ingo; Borisow, Nadja; Asgari, Nasrin; Pitarokoili, Kalliopi; Pache, Florence; Stich, Oliver; Beume, Lena Alexandra; Hümmert, Martin W.; Trebst, Corinna; Ringelstein, Marius; Aktas, Orhan; Winkelmann, Alexander; Buttmann, Mathias; Schwarz, Alexander; Zimmermann, Hanna; Brandt, Alexander U.; Franciotta, Diego; Capobianco, Marco; Kuchling, Joseph; Haas, Jürgen; Korporal-Kuhnke, Mirjam; Lillevang, Soeren Thue; Fechner, Kai; Schanda, Kathrin; Paul, Friedemann; Wildemann, Brigitte; Reindl, Markus; in cooperation with the Neuromyelitis Optica Study Group (NEMOS).

In: Journal of Neuroinflammation, Vol. 13, No. 1, 279, 26.09.2016.

Research output: Contribution to journalArticle

Jarius, S, Ruprecht, K, Kleiter, I, Borisow, N, Asgari, N, Pitarokoili, K, Pache, F, Stich, O, Beume, LA, Hümmert, MW, Trebst, C, Ringelstein, M, Aktas, O, Winkelmann, A, Buttmann, M, Schwarz, A, Zimmermann, H, Brandt, AU, Franciotta, D, Capobianco, M, Kuchling, J, Haas, J, Korporal-Kuhnke, M, Lillevang, ST, Fechner, K, Schanda, K, Paul, F, Wildemann, B, Reindl, M & in cooperation with the Neuromyelitis Optica Study Group (NEMOS) 2016, 'MOG-IgG in NMO and related disorders: A multicenter study of 50 patients. Part 1: Frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin', Journal of Neuroinflammation, vol. 13, no. 1, 279. https://doi.org/10.1186/s12974-016-0717-1
Jarius, Sven ; Ruprecht, Klemens ; Kleiter, Ingo ; Borisow, Nadja ; Asgari, Nasrin ; Pitarokoili, Kalliopi ; Pache, Florence ; Stich, Oliver ; Beume, Lena Alexandra ; Hümmert, Martin W. ; Trebst, Corinna ; Ringelstein, Marius ; Aktas, Orhan ; Winkelmann, Alexander ; Buttmann, Mathias ; Schwarz, Alexander ; Zimmermann, Hanna ; Brandt, Alexander U. ; Franciotta, Diego ; Capobianco, Marco ; Kuchling, Joseph ; Haas, Jürgen ; Korporal-Kuhnke, Mirjam ; Lillevang, Soeren Thue ; Fechner, Kai ; Schanda, Kathrin ; Paul, Friedemann ; Wildemann, Brigitte ; Reindl, Markus ; in cooperation with the Neuromyelitis Optica Study Group (NEMOS). / MOG-IgG in NMO and related disorders : A multicenter study of 50 patients. Part 1: Frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin. In: Journal of Neuroinflammation. 2016 ; Vol. 13, No. 1.
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title = "MOG-IgG in NMO and related disorders: A multicenter study of 50 patients. Part 1: Frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin",
abstract = "Background: Antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) have been suggested to play a role in a subset of patients with neuromyelitis optica and related disorders. Objective: To assess (i) the frequency of MOG-IgG in a large and predominantly Caucasian cohort of patients with optic neuritis (ON) and/or myelitis; (ii) the frequency of MOG-IgG among AQP4-IgG-positive patients and vice versa; (iii) the origin and frequency of MOG-IgG in the cerebrospinal fluid (CSF); (iv) the presence of MOG-IgG at disease onset; and (v) the influence of disease activity and treatment status on MOG-IgG titers. Methods: 614 serum samples from patients with ON and/or myelitis and from controls, including 92 follow-up samples from 55 subjects, and 18 CSF samples were tested for MOG-IgG using a live cell-based assay (CBA) employing full-length human MOG-transfected HEK293A cells. Results: MOG-IgG was detected in 95 sera from 50 patients with ON and/or myelitis, including 22/54 (40.7 {\%}) patients with a history of both ON and myelitis, 22/103 (21.4 {\%}) with a history of ON but no myelitis and 6/45 (13.3 {\%}) with a history of longitudinally extensive transverse myelitis but no ON, and in 1 control patient with encephalitis and a connective tissue disorder, all of whom were negative for AQP4-IgG. MOG-IgG was absent in 221 further controls, including 83 patients with AQP4-IgG-seropositive neuromyelitis optica spectrum disorders and 85 with multiple sclerosis (MS). MOG-IgG was found in 12/18 (67 {\%}) CSF samples from MOG-IgG-seropositive patients; the MOG-IgG-specific antibody index was negative in all cases, indicating a predominantly peripheral origin of CSF MOG-IgG. Serum and CSF MOG-IgG belonged to the complement-activating IgG1 subclass. MOG-IgG was present already at disease onset. The antibodies remained detectable in 40/45 (89 {\%}) follow-up samples obtained over a median period of 16.5 months (range 0-123). Serum titers were higher during attacks than during remission (p < 0.0001), highest during attacks of simultaneous myelitis and ON, lowest during acute isolated ON, and declined following treatment. Conclusions: To date, this is the largest cohort studied for IgG to human full-length MOG by means of an up-to-date CBA. MOG-IgG is present in a substantial subset of patients with ON and/or myelitis, but not in classical MS. Co-existence of MOG-IgG and AQP4-IgG is highly uncommon. CSF MOG-IgG is of extrathecal origin. Serum MOG-IgG is present already at disease onset and remains detectable in the long-term course. Serum titers depend on disease activity and treatment status.",
keywords = "Antibody index, Aquaporin-4 antibodies (AQP4-IgG), Autoantibodies, Cell-based assays, Cerebrospinal fluid, Devic's syndrome, Longitudinally extensive transverse myelitis (LETM), Multiple sclerosis, Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG), Neuromyelitis optica (NMO), Neuromyelitis optica antibodies (NMO-IgG), Neuromyelitis optica spectrum disorders (NMOSD), Optic neuritis, Transverse Myelitis",
author = "Sven Jarius and Klemens Ruprecht and Ingo Kleiter and Nadja Borisow and Nasrin Asgari and Kalliopi Pitarokoili and Florence Pache and Oliver Stich and Beume, {Lena Alexandra} and H{\"u}mmert, {Martin W.} and Corinna Trebst and Marius Ringelstein and Orhan Aktas and Alexander Winkelmann and Mathias Buttmann and Alexander Schwarz and Hanna Zimmermann and Brandt, {Alexander U.} and Diego Franciotta and Marco Capobianco and Joseph Kuchling and J{\"u}rgen Haas and Mirjam Korporal-Kuhnke and Lillevang, {Soeren Thue} and Kai Fechner and Kathrin Schanda and Friedemann Paul and Brigitte Wildemann and Markus Reindl and {in cooperation with the Neuromyelitis Optica Study Group (NEMOS)}",
year = "2016",
month = "9",
day = "26",
doi = "10.1186/s12974-016-0717-1",
language = "English",
volume = "13",
journal = "Journal of Neuroinflammation",
issn = "1742-2094",
publisher = "NLM (Medline)",
number = "1",

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TY - JOUR

T1 - MOG-IgG in NMO and related disorders

T2 - A multicenter study of 50 patients. Part 1: Frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin

AU - Jarius, Sven

AU - Ruprecht, Klemens

AU - Kleiter, Ingo

AU - Borisow, Nadja

AU - Asgari, Nasrin

AU - Pitarokoili, Kalliopi

AU - Pache, Florence

AU - Stich, Oliver

AU - Beume, Lena Alexandra

AU - Hümmert, Martin W.

AU - Trebst, Corinna

AU - Ringelstein, Marius

AU - Aktas, Orhan

AU - Winkelmann, Alexander

AU - Buttmann, Mathias

AU - Schwarz, Alexander

AU - Zimmermann, Hanna

AU - Brandt, Alexander U.

AU - Franciotta, Diego

AU - Capobianco, Marco

AU - Kuchling, Joseph

AU - Haas, Jürgen

AU - Korporal-Kuhnke, Mirjam

AU - Lillevang, Soeren Thue

AU - Fechner, Kai

AU - Schanda, Kathrin

AU - Paul, Friedemann

AU - Wildemann, Brigitte

AU - Reindl, Markus

AU - in cooperation with the Neuromyelitis Optica Study Group (NEMOS)

PY - 2016/9/26

Y1 - 2016/9/26

N2 - Background: Antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) have been suggested to play a role in a subset of patients with neuromyelitis optica and related disorders. Objective: To assess (i) the frequency of MOG-IgG in a large and predominantly Caucasian cohort of patients with optic neuritis (ON) and/or myelitis; (ii) the frequency of MOG-IgG among AQP4-IgG-positive patients and vice versa; (iii) the origin and frequency of MOG-IgG in the cerebrospinal fluid (CSF); (iv) the presence of MOG-IgG at disease onset; and (v) the influence of disease activity and treatment status on MOG-IgG titers. Methods: 614 serum samples from patients with ON and/or myelitis and from controls, including 92 follow-up samples from 55 subjects, and 18 CSF samples were tested for MOG-IgG using a live cell-based assay (CBA) employing full-length human MOG-transfected HEK293A cells. Results: MOG-IgG was detected in 95 sera from 50 patients with ON and/or myelitis, including 22/54 (40.7 %) patients with a history of both ON and myelitis, 22/103 (21.4 %) with a history of ON but no myelitis and 6/45 (13.3 %) with a history of longitudinally extensive transverse myelitis but no ON, and in 1 control patient with encephalitis and a connective tissue disorder, all of whom were negative for AQP4-IgG. MOG-IgG was absent in 221 further controls, including 83 patients with AQP4-IgG-seropositive neuromyelitis optica spectrum disorders and 85 with multiple sclerosis (MS). MOG-IgG was found in 12/18 (67 %) CSF samples from MOG-IgG-seropositive patients; the MOG-IgG-specific antibody index was negative in all cases, indicating a predominantly peripheral origin of CSF MOG-IgG. Serum and CSF MOG-IgG belonged to the complement-activating IgG1 subclass. MOG-IgG was present already at disease onset. The antibodies remained detectable in 40/45 (89 %) follow-up samples obtained over a median period of 16.5 months (range 0-123). Serum titers were higher during attacks than during remission (p < 0.0001), highest during attacks of simultaneous myelitis and ON, lowest during acute isolated ON, and declined following treatment. Conclusions: To date, this is the largest cohort studied for IgG to human full-length MOG by means of an up-to-date CBA. MOG-IgG is present in a substantial subset of patients with ON and/or myelitis, but not in classical MS. Co-existence of MOG-IgG and AQP4-IgG is highly uncommon. CSF MOG-IgG is of extrathecal origin. Serum MOG-IgG is present already at disease onset and remains detectable in the long-term course. Serum titers depend on disease activity and treatment status.

AB - Background: Antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) have been suggested to play a role in a subset of patients with neuromyelitis optica and related disorders. Objective: To assess (i) the frequency of MOG-IgG in a large and predominantly Caucasian cohort of patients with optic neuritis (ON) and/or myelitis; (ii) the frequency of MOG-IgG among AQP4-IgG-positive patients and vice versa; (iii) the origin and frequency of MOG-IgG in the cerebrospinal fluid (CSF); (iv) the presence of MOG-IgG at disease onset; and (v) the influence of disease activity and treatment status on MOG-IgG titers. Methods: 614 serum samples from patients with ON and/or myelitis and from controls, including 92 follow-up samples from 55 subjects, and 18 CSF samples were tested for MOG-IgG using a live cell-based assay (CBA) employing full-length human MOG-transfected HEK293A cells. Results: MOG-IgG was detected in 95 sera from 50 patients with ON and/or myelitis, including 22/54 (40.7 %) patients with a history of both ON and myelitis, 22/103 (21.4 %) with a history of ON but no myelitis and 6/45 (13.3 %) with a history of longitudinally extensive transverse myelitis but no ON, and in 1 control patient with encephalitis and a connective tissue disorder, all of whom were negative for AQP4-IgG. MOG-IgG was absent in 221 further controls, including 83 patients with AQP4-IgG-seropositive neuromyelitis optica spectrum disorders and 85 with multiple sclerosis (MS). MOG-IgG was found in 12/18 (67 %) CSF samples from MOG-IgG-seropositive patients; the MOG-IgG-specific antibody index was negative in all cases, indicating a predominantly peripheral origin of CSF MOG-IgG. Serum and CSF MOG-IgG belonged to the complement-activating IgG1 subclass. MOG-IgG was present already at disease onset. The antibodies remained detectable in 40/45 (89 %) follow-up samples obtained over a median period of 16.5 months (range 0-123). Serum titers were higher during attacks than during remission (p < 0.0001), highest during attacks of simultaneous myelitis and ON, lowest during acute isolated ON, and declined following treatment. Conclusions: To date, this is the largest cohort studied for IgG to human full-length MOG by means of an up-to-date CBA. MOG-IgG is present in a substantial subset of patients with ON and/or myelitis, but not in classical MS. Co-existence of MOG-IgG and AQP4-IgG is highly uncommon. CSF MOG-IgG is of extrathecal origin. Serum MOG-IgG is present already at disease onset and remains detectable in the long-term course. Serum titers depend on disease activity and treatment status.

KW - Antibody index

KW - Aquaporin-4 antibodies (AQP4-IgG)

KW - Autoantibodies

KW - Cell-based assays

KW - Cerebrospinal fluid

KW - Devic's syndrome

KW - Longitudinally extensive transverse myelitis (LETM)

KW - Multiple sclerosis

KW - Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG)

KW - Neuromyelitis optica (NMO)

KW - Neuromyelitis optica antibodies (NMO-IgG)

KW - Neuromyelitis optica spectrum disorders (NMOSD)

KW - Optic neuritis

KW - Transverse Myelitis

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U2 - 10.1186/s12974-016-0717-1

DO - 10.1186/s12974-016-0717-1

M3 - Article

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JO - Journal of Neuroinflammation

JF - Journal of Neuroinflammation

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