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Myelin injury without astrocytopathy in neuroinflammatory disorders with MOG antibodies
  1. Kimihiko Kaneko1,
  2. Douglas Kazutoshi Sato1,2,
  3. Ichiro Nakashima1,
  4. Shuhei Nishiyama1,
  5. Satoru Tanaka3,
  6. Romain Marignier4,
  7. Jae-Won Hyun5,
  8. Luana Michelli de Oliveira2,
  9. Markus Reindl6,
  10. Thomas Seifert-Held7,
  11. Maria Sepulveda8,
  12. Sasitorn Siritho9,
  13. Patrick Joseph Waters10,
  14. Kazuhiro Kurosawa1,
  15. Tetsuya Akaishi1,
  16. Hiroshi Kuroda1,
  17. Tatsuro Misu2,
  18. Naraporn Prayoonwiwat9,
  19. Thomas Berger6,
  20. Albert Saiz8,
  21. Ho Jin Kim5,
  22. Kyoichi Nomura3,
  23. Dagoberto Callegaro2,
  24. Kazuo Fujihara1,
  25. Masashi Aoki1
  1. 1Departments of Neurology and Multiple Sclerosis Therapeutics, Tohoku University Graduate School of Medicine, Sendai, Japan
  2. 2Faculty of Medicine, Department of Neurology, University of São Paulo, São Paulo, Brazil
  3. 3Department of Neurology, Saitama Medical Center, Kawagoe, Japan
  4. 4Lyon Neuroscience Research Center INSERM U 1028/CNRS 5292, Lyon, France
  5. 5Research Institute and Hospital of National Cancer Center, Seoul, Republic of Korea
  6. 6Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
  7. 7Department of Neurology, Medical University of Graz, Graz, Austria
  8. 8Service of Neurology, Hospital Clinic and Institute d'Investigación Biomèdica August Pi Sunyer, University of Barcelona, Barcelona, Spain
  9. 9Department of Neurology, Siriraj Hospital, Mahidol University, Bangkok, Thailand
  10. 10Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
  1. Correspondence to Dr Douglas Kazutoshi Sato, Department of Multiple Sclerosis Therapeutics, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Miyagi, Japan; douglas.sato{at}med.tohoku.ac.jp

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Background

Acquired inflammatory central nervous system (CNS) disorders include multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), acute disseminated encephalomyelitis (ADEM), optic neuritis (ON), transverse myelitis and other less prevalent disorders.1 Differential diagnosis between these entities may be challenging in some cases due to overlapping clinical characteristics.

Antibodies against aquaporin-4 (AQP4-Ab) suggest the diagnosis of NMOSD and promote severe immune-mediated astrocyte damage. However, some patients who are clinically diagnosed with NMOSD are AQP4-Ab-seronegative despite the use of highly sensitive cell-based assays (CBAs); therefore, other CNS molecules may be implicated as autoimmune targets in such cases.

Recently, we reported the presence of conformational-sensitive antibodies against myelin oligodendrocyte glycoprotein (MOG-Ab) in a portion of AQP4-Ab-seronegative NMOSD,2 ADEM and ON cases, but these antibodies are not usually found in typical MS, using highly specific CBAs.

Thus, it is interesting to study how MOG-Ab+ cases pathologically and immunologically differ from AQP4-Ab+ cases and MS cases. In this multicentre international collaborative study, we evaluated MOG-Ab and AQP4-Ab antibodies in the CSF, and compared markers of myelin and astrocyte damage in the CSF as well as other routine CSF parameters between the three groups.

Patients and methods

We enrolled a total of 90 patients diagnosed with acquired inflammatory CNS disorders and serum positivity for MOG-Ab or AQP4-Ab antibodies, using CBAs from Japan, Brazil, Republic of Korea, Spain, France, Austria and Thailand. For the European countries, serum antibody testing was performed in each respective country. We also included CSF samples from 40 relapsing-remitting patients with MS who fulfilled the 2010 McDonald criteria3 and 16 samples from patients with non-inflammatory neurological disorders (spinal cord infarction, cerebral infarction, spinocerebellar degeneration=2, Parkinson's disease=2, progressive supranuclear palsy=2, amyotrophic lateral sclerosis=2, Alzheimer dementia=1, NPH=1, migraine=2, somatoform disorder=2) as controls. All samples were shipped in dry ice to Sendai, Japan, and stored at −80°C …

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