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Anti-MOG antibody–associated disorders: differences in clinical profiles and prognosis in Japan and Germany
  1. Jia Liu1,
  2. Masahiro Mori1,
  3. Hanna Zimmermann2,3,
  4. Alexander Brandt2,3,4,
  5. Joachim Havla5,
  6. Satoru Tanaka6,
  7. Kazuo Sugimoto1,
  8. Satoru Oji6,
  9. Akiyuki Uzawa1,
  10. Susanna Asseyer2,3,
  11. Graham Cooper2,3,7,8,
  12. Sven Jarius9,
  13. Judith Bellmann-Strobl2,3,
  14. Klemens Ruprecht10,
  15. Nadja Siebert2,3,
  16. Hiroki Masuda1,
  17. Tomohiko Uchida1,
  18. Ryohei Ohtani1,
  19. Kyoichi Nomura6,
  20. Edgar Meinl5,
  21. Tania Kuempfel5,
  22. Friedemann Paul2,3,7,10,
  23. Satoshi Kuwabara1
  1. 1Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan
  2. 2Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine and Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
  3. 3NeuroCure Clinical Research Center, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
  4. 4Department of Neurology, University of California, Irvine, California, USA
  5. 5Institute of Clinical Neuroimmunology, LMU-Hospital, Ludwig-Maximilians Universiät München, Munich, Germany
  6. 6Department of Neurology, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan
  7. 7Einstein Center for Neurosciences, Berlin, Germany
  8. 8Department of Experimental Neurology and Center for Stroke Research, Berlin, Charité – Universitätsmedizin Berlin, Berlin, Germany
  9. 9Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany
  10. 10Department of Neurology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
  1. Correspondence to Professor Satoshi Kuwabara, Neurology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan; kuwabara-s{at}faculty.chiba-u.jp

Abstract

Background Neurological disorders with IgG antibodies against myelin-oligodendrocyte glycoprotein (MOG-IgG) have been increasingly recognised as a new type of neuroinflammatory disorder.

Objective The study aimed to identify regional and ethnic differences in clinical profiles of MOG-IgG–associated disorders between East Asian (Japanese) and Caucasian (German) patients.

Methods Demographic, clinical and therapeutic data from 68 MOG-IgG–positive adults were collected (Japanese, n=44; German, n=24).

Results Age and sex were similar between cohorts, with optic neuritis occurring most frequently at onset (Japanese: 61%; German: 58%). However, Japanese patients had a lower annualised relapse rate (0.4 vs 0.8, p=0.019; no relapse, 64% vs 25%, p=0.002) and lower Expanded Disability Status Scale score at the last visit (1.0 vs 2.0; p=0.008), despite similar follow-up periods (mean, 73.9 months vs 73.4 months), than those of German patients, respectively. Cerebral syndromes were more common (27% vs 4%; p=0.021) and myelitis less common (21% vs 50%; p=0.012) in Japanese than in German patients, respectively. Japanese patients were more commonly treated with long-term corticosteroids (73%), whereas German patients were more commonly treated with rituximab or other immunosuppressants (63%).

Conclusions Among patients with MOG-IgG, Japanese tended to have a monophasic milder disease, whereas the majority of German patients had a relapsing course and more frequent myelitis, findings compatible with neuromyelitis optica spectrum disorder. Although the attack-prevention treatment regimens were considerably different, genetic and environmental factors may be important to determine clinical phenotypes and disease activity.

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Footnotes

  • JL, FP and SK are joint senior authors.

  • Contributors JL, MM, HZ, FP and SK conceived the study concept and design and drafted the manuscript; AB, ST, JH, HZ, SO, AU, SA, GC, SJ, JB-S, KR, NS, HM, TU, RO, KN, EM and TK enrolled patients and collected the data; and JL and MM performed statistical analyses. JH and TK enrolled patients, collected the data and contributed to the critical revision of the manuscript. FP and SK supervised the study. All authors approved the final manuscript for submission.

  • Funding This work was supported in part by the Health and Labour Sciences Research Grant on Intractable Diseases (Neuroimmunological Diseases) and the Research Grant 16B-1 for Nervous and Mental Disorders from the Ministry of Health, Labour and Welfare of Japan; and by NeuroCure Clinical Research Center (NCRC), funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy – EXC-2049 – 390688087 and by the SFB-TR128 and by the Research Grant “CC-Neuro” from the German Federal Ministry of Education and Research. JH is (partially) funded by the German Federal Ministry of Education and Research (Grant Numbers 01ZZ1603[A-D] and 01ZZ1804[A-H] (DIFUTURE)).

  • Competing interests HZ received research grants from Novartis and speaking honoraria from Bayer Healthcare. JH is reviewing editor in the Frontiers in Neurology/Frontiers in Immunology. JH reports grants for neurovisual research from the Friedrich-Baur-Stiftung and Merck, personal fees and non-financial support from Celgene, Merck, Alexion, Novartis, Roche, Santhera, Biogen, Heidelberg Engineering, Sanofi Genzyme and non-financial support of the Guthy-Jackson Charitable Foundation, all outside the submitted work. SA received travel grant from Celgene and speaker’s honorary from Roche and Bayer, unrelated to this project. GC received speaker honoraria from Merck Serono and Bayer Healthcare, unrelated to this project. EM is reviewing editor in the Journal of Biological Chemistry, editor in the Journal of Pathology, associate editor in Frontiers in Neurology and Frontiers in Immunology, editor in PLOS-One, received honorarium from Roche, Novartis, Sanofi, Biogen and Bioeq and grant support from Novartis, Sanofi and Merck. SJ was indirectly supported by research grants from the Dietmar Hopp Foundation and from Merck Serono to the Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany. TK has received speaker honoraria including advisory boards from Bayer Healthcare, Teva Pharma, Merck, Novartis Pharma, Sanofi-Aventis/Genzyme, Roche Pharma and Biogen as well as grant support from Novartis and Chugai Pharma in the past. FP serves as an Associate Editor for Neurology: Neuroimmunology & Neuroinflammation, reports research grants and speaker honoraria from Bayer, Teva, Genzyme, Merck, Novartis, MedImmune and is member of the steering committee of the OCTIMS study (Novartis). SK serves as the Deputy Editor of the Journal of Neurology, Neurosurgery, and Psychiatry and is an Editorial Board member of the Journal of the Neurological Sciences.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request. The deidentified participant data are available on reasonable request to person who provide his/her name, affiliation, title and email address.

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