Review

. 2018 Mar 19;15(1):88.

doi: 10.1186/s12974-018-1108-6.

MOG-IgG in primary and secondary chronic progressive multiple sclerosis: a multicenter study of 200 patients and review of the literature

S Jarius^{1

2}, K Ruprecht³, J P Stellmann^{4

5}, A Huss⁶, I Ayzenberg⁷, A Willing⁴, C Trebst⁸, M Pawlitzki⁹, A Abdelhak⁶, T Grüter⁷, F Leypoldt¹⁰, J Haas¹¹, I Kleiter^{7

12}, H Tumani^{6

13}, K Fechner¹⁴, M Reindl¹⁵, F Paul^{3

16

17}, B Wildemann^{18

19}

Affiliations

¹ Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany. sven.jarius@med.uni-heidelberg.de.
² Otto Meyerhof Center, Im Neuenheimer Feld 350, 69120, Heidelberg, Germany. sven.jarius@med.uni-heidelberg.de.
³ Department of Neurology, Charité - University Medicine Berlin, Berlin, Germany.
⁴ Institut für Neuroimmunologie und Multiple Sklerose (INIMS), Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
⁵ Klinik und Poliklinik für Neurologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
⁶ Department of Neurology, University of Ulm, Ulm, Germany.
⁷ Department of Neurology, Ruhr University Bochum, Bochum, Germany.
⁸ Department of Neurology, Hannover Medical School, Hanover, Germany.
⁹ Department of Neurology, Otto von Guericke University Magdeburg, Magdeburg, Germany.
¹⁰ Department of Neurology and Institute of Laboratory Medicine, University Hospital Schleswig-Holstein, Kiel, Germany.
¹¹ Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany.
¹² Marianne-Strauß-Klinik, Behandlungszentrum Kempfenhausen für Multiple Sklerose Kranke, Berg, Germany.
¹³ Specialty Clinic of Neurology Dietenbronn, Schwendi, Germany.
¹⁴ Institute of Experimental Immunology, affiliated to Euroimmun AG, Lübeck, Germany.
¹⁵ Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
¹⁶ NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
¹⁷ Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
¹⁸ Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany. brigitte.wildemann@med.uni-heidelberg.de.
¹⁹ Otto Meyerhof Center, Im Neuenheimer Feld 350, 69120, Heidelberg, Germany. brigitte.wildemann@med.uni-heidelberg.de.

PMID: 29554927
PMCID: PMC5859439
DOI: 10.1186/s12974-018-1108-6

Review

MOG-IgG in primary and secondary chronic progressive multiple sclerosis: a multicenter study of 200 patients and review of the literature

S Jarius et al. J Neuroinflammation. 2018.

. 2018 Mar 19;15(1):88.

doi: 10.1186/s12974-018-1108-6.

Authors

Affiliations

¹ Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany. sven.jarius@med.uni-heidelberg.de.
² Otto Meyerhof Center, Im Neuenheimer Feld 350, 69120, Heidelberg, Germany. sven.jarius@med.uni-heidelberg.de.
³ Department of Neurology, Charité - University Medicine Berlin, Berlin, Germany.
⁴ Institut für Neuroimmunologie und Multiple Sklerose (INIMS), Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
⁵ Klinik und Poliklinik für Neurologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
⁶ Department of Neurology, University of Ulm, Ulm, Germany.
⁷ Department of Neurology, Ruhr University Bochum, Bochum, Germany.
⁸ Department of Neurology, Hannover Medical School, Hanover, Germany.
⁹ Department of Neurology, Otto von Guericke University Magdeburg, Magdeburg, Germany.
¹⁰ Department of Neurology and Institute of Laboratory Medicine, University Hospital Schleswig-Holstein, Kiel, Germany.
¹¹ Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany.
¹² Marianne-Strauß-Klinik, Behandlungszentrum Kempfenhausen für Multiple Sklerose Kranke, Berg, Germany.
¹³ Specialty Clinic of Neurology Dietenbronn, Schwendi, Germany.
¹⁴ Institute of Experimental Immunology, affiliated to Euroimmun AG, Lübeck, Germany.
¹⁵ Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
¹⁶ NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
¹⁷ Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
¹⁸ Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany. brigitte.wildemann@med.uni-heidelberg.de.
¹⁹ Otto Meyerhof Center, Im Neuenheimer Feld 350, 69120, Heidelberg, Germany. brigitte.wildemann@med.uni-heidelberg.de.

PMID: 29554927
PMCID: PMC5859439
DOI: 10.1186/s12974-018-1108-6

Abstract

Background: Antibodies to human full-length myelin oligodendrocyte glycoprotein (MOG-IgG) as detected by new-generation cell-based assays have recently been described in patients presenting with acute demyelinating disease of the central nervous system, including patients previously diagnosed with multiple sclerosis (MS). However, only limited data are available on the relevance of MOG-IgG testing in patients with chronic progressive demyelinating disease. It is unclear if patients with primary progressive MS (PPMS) or secondary progressive MS (SPMS) should routinely be tested for MOG-IgG.

Objective: To evaluate the frequency of MOG-IgG among patients classified as having PPMS or SPMS based on current diagnostic criteria.

Methods: For this purpose, we retrospectively tested serum samples of 200 patients with PPMS or SPMS for MOG-IgG using cell-based assays. In addition, we performed a review of the entire English language literature on MOG-IgG published between 2011 and 2017.

Results: None of 139 PPMS and 61 SPMS patients tested was positive for MOG-IgG. Based on a review of the literature, we identified 35 further MOG-IgG tests in patients with PPMS and 55 in patients with SPMS; the only reportedly positive sample was positive just at threshold level and was tested in a non-IgG-specific assay. In total, a single borderline positive result was observed among 290 tests.

Conclusion: Our data suggest that MOG-IgG is absent or extremely rare among patients with PPMS or SPMS. Routine screening of patients with typical PPMS/SPMS for MOG-IgG seems not to be justified.

Keywords: Antibodies; Immunoglobulin G; MOG-IgG; Myelin oligodendrocyte glycoprotein (MOG); Neuromyelitis optica spectrum disorders (NMOSD); Primary chronic progressive MS (PPMS); Secondary chronic progressive MS (SPMS).

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

The study was approved by the institutional review boards of the participating centers. Patients gave written informed consent or were tested in an anonymised fashion as requested by the institutional review board of the University of Heidelberg.

Consent for publication

Not applicable.

Competing interests

BW has received research grants, speaking fees, and travel grants from Merck Serono, Biogen, Teva, Novartis, Sanofi Genzyme, Bayer Healthcare, the Klaus Tschira Stiftung, and the Dietmar Hopp Stiftung. JPS has received research grants and speaking fees from DFG, Biogen, and Genzyme not related to the present work. KR has received research grants from German Ministry of Education and Research (BMBF/KKNMS, Competence Network Multiple Sclerosis), Novartis, Merck Serono, and the Charité Research Fund; honoraria for consultancy or speaking and travel reimbursement from Novartis, Bayer Healthcare, Biogen Idec, Merck Serono, sanofi-aventis/Genzyme, Teva Pharmaceuticals, and Guthy Jackson Charitable Foundation; all unrelated to the submitted work. MP received research grants, speaker honoraria, and travel/accommodation/meeting expenses from Novartis, and speaker honoraria from Genzyme, Biogen Idec., Merck Serono, and Roche. I.K. received honoraria for consultancy or speaking and travel reimbursement from Bayer Healthcare, Biogen, Chugai, Merck, Novartis, Roche, and Shire, and research support from Affectis, Biogen, Chugai and Diamed, all not related to the presented work. CT has received honoraria for consultation and expert testimony from Biogen Idec/GmbH, Genzyme GmbH and Novartis Pharmaceuticals; none of this interfered with the current report. K.F. is an employee of Euroimmun AG, Germany. FL is employed by a non-commercial academic institution (University Hospital Schlewsig-Holstein) offering antibody testing. The University Hospital and Medical University of Innsbruck (Austria; M.R.) receives payments for antibody assays (MOG, AQP4, and other autoantibodies) and for MOG and AQP4 antibody validation experiments organized by Euroimmun (Lübeck, Germany). All authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

1. Reindl M, Jarius S, Rostasy K, Berger T. Myelin oligodendrocyte glycoprotein antibodies: how clinically useful are they? Curr Opin Neurol. 2017;30:295–301. doi: 10.1097/WCO.0000000000000446. - DOI - PubMed
1. Jarius S, Kleiter I, Ruprecht K, Asgari N, Pitarokoili K, Borisow N, Hummert MW, Trebst C, Pache F, Winkelmann A, et al. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 3: brainstem involvement—frequency, presentation and outcome. J Neuroinflammation. 2016;13:281. doi: 10.1186/s12974-016-0719-z. - DOI - PMC - PubMed
1. Jarius S, Ruprecht K, Kleiter I, Borisow N, Asgari N, Pitarokoili K, Pache F, Stich O, Beume LA, Hummert MW, et al. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 2: epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome. J Neuroinflammation. 2016;13:280. doi: 10.1186/s12974-016-0718-0. - DOI - PMC - PubMed
1. Jarius S, Ruprecht K, Kleiter I, Borisow N, Asgari N, Pitarokoili K, Pache F, Stich O, Beume LA, Hummert MW, et al. 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. J Neuroinflammation. 2016;13:279. doi: 10.1186/s12974-016-0717-1. - DOI - PMC - PubMed
1. Pache F, Zimmermann H, Mikolajczak J, Schumacher S, Lacheta A, Oertel FC, Bellmann-Strobl J, Jarius S, Wildemann B, Reindl M, et al. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 4: afferent visual system damage after optic neuritis in MOG-IgG-seropositive versus AQP4-IgG-seropositive patients. J Neuroinflammation. 2016;13:282. doi: 10.1186/s12974-016-0720-6. - DOI - PMC - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions

LinkOut - more resources

Full Text Sources
- Europe PubMed Central
Other Literature Sources
- scite Smart Citations

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

MOG-IgG in primary and secondary chronic progressive multiple sclerosis: a multicenter study of 200 patients and review of the literature

Affiliations

MOG-IgG in primary and secondary chronic progressive multiple sclerosis: a multicenter study of 200 patients and review of the literature

Authors

Affiliations

Abstract

Conflict of interest statement

Ethics approval and consent to participate

Consent for publication

Competing interests

Publisher’s Note

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Other Literature Sources