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February 11, 2014; 82 (6) Article

Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders

Douglas Kazutoshi Sato, Dagoberto Callegaro, Marco Aurelio Lana-Peixoto, Patrick J. Waters, Frederico M. de Haidar Jorge, Toshiyuki Takahashi, Ichiro Nakashima, Samira Luisa Apostolos-Pereira, Natalia Talim, Renata Faria Simm, Angelina Maria Martins Lino, Tatsuro Misu, Maria Isabel Leite, Masashi Aoki, Kazuo Fujihara
First published January 10, 2014, DOI: https://doi.org/10.1212/WNL.0000000000000101
Douglas Kazutoshi Sato
From the Departments of Neurology (D.K.S., T.T., I.N., M.A.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Neurology (D.C., F.M.d.H.J., S.L.A.-P., R.F.S., A.M.M.L.), Faculty of Medicine, University of São Paulo, Brazil; CIEM MS Research Center (M.A.L.-P., N.T.), Federal University of Minas Gerais Medical School, Belo Horizonte, Brazil; Neuroimmunology Group (P.J.W., M.I.L.), Nuffield Department of Clinical Neurosciences, Oxford University, UK.
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Dagoberto Callegaro
From the Departments of Neurology (D.K.S., T.T., I.N., M.A.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Neurology (D.C., F.M.d.H.J., S.L.A.-P., R.F.S., A.M.M.L.), Faculty of Medicine, University of São Paulo, Brazil; CIEM MS Research Center (M.A.L.-P., N.T.), Federal University of Minas Gerais Medical School, Belo Horizonte, Brazil; Neuroimmunology Group (P.J.W., M.I.L.), Nuffield Department of Clinical Neurosciences, Oxford University, UK.
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Marco Aurelio Lana-Peixoto
From the Departments of Neurology (D.K.S., T.T., I.N., M.A.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Neurology (D.C., F.M.d.H.J., S.L.A.-P., R.F.S., A.M.M.L.), Faculty of Medicine, University of São Paulo, Brazil; CIEM MS Research Center (M.A.L.-P., N.T.), Federal University of Minas Gerais Medical School, Belo Horizonte, Brazil; Neuroimmunology Group (P.J.W., M.I.L.), Nuffield Department of Clinical Neurosciences, Oxford University, UK.
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Patrick J. Waters
From the Departments of Neurology (D.K.S., T.T., I.N., M.A.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Neurology (D.C., F.M.d.H.J., S.L.A.-P., R.F.S., A.M.M.L.), Faculty of Medicine, University of São Paulo, Brazil; CIEM MS Research Center (M.A.L.-P., N.T.), Federal University of Minas Gerais Medical School, Belo Horizonte, Brazil; Neuroimmunology Group (P.J.W., M.I.L.), Nuffield Department of Clinical Neurosciences, Oxford University, UK.
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Frederico M. de Haidar Jorge
From the Departments of Neurology (D.K.S., T.T., I.N., M.A.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Neurology (D.C., F.M.d.H.J., S.L.A.-P., R.F.S., A.M.M.L.), Faculty of Medicine, University of São Paulo, Brazil; CIEM MS Research Center (M.A.L.-P., N.T.), Federal University of Minas Gerais Medical School, Belo Horizonte, Brazil; Neuroimmunology Group (P.J.W., M.I.L.), Nuffield Department of Clinical Neurosciences, Oxford University, UK.
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Toshiyuki Takahashi
From the Departments of Neurology (D.K.S., T.T., I.N., M.A.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Neurology (D.C., F.M.d.H.J., S.L.A.-P., R.F.S., A.M.M.L.), Faculty of Medicine, University of São Paulo, Brazil; CIEM MS Research Center (M.A.L.-P., N.T.), Federal University of Minas Gerais Medical School, Belo Horizonte, Brazil; Neuroimmunology Group (P.J.W., M.I.L.), Nuffield Department of Clinical Neurosciences, Oxford University, UK.
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Ichiro Nakashima
From the Departments of Neurology (D.K.S., T.T., I.N., M.A.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Neurology (D.C., F.M.d.H.J., S.L.A.-P., R.F.S., A.M.M.L.), Faculty of Medicine, University of São Paulo, Brazil; CIEM MS Research Center (M.A.L.-P., N.T.), Federal University of Minas Gerais Medical School, Belo Horizonte, Brazil; Neuroimmunology Group (P.J.W., M.I.L.), Nuffield Department of Clinical Neurosciences, Oxford University, UK.
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Samira Luisa Apostolos-Pereira
From the Departments of Neurology (D.K.S., T.T., I.N., M.A.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Neurology (D.C., F.M.d.H.J., S.L.A.-P., R.F.S., A.M.M.L.), Faculty of Medicine, University of São Paulo, Brazil; CIEM MS Research Center (M.A.L.-P., N.T.), Federal University of Minas Gerais Medical School, Belo Horizonte, Brazil; Neuroimmunology Group (P.J.W., M.I.L.), Nuffield Department of Clinical Neurosciences, Oxford University, UK.
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Natalia Talim
From the Departments of Neurology (D.K.S., T.T., I.N., M.A.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Neurology (D.C., F.M.d.H.J., S.L.A.-P., R.F.S., A.M.M.L.), Faculty of Medicine, University of São Paulo, Brazil; CIEM MS Research Center (M.A.L.-P., N.T.), Federal University of Minas Gerais Medical School, Belo Horizonte, Brazil; Neuroimmunology Group (P.J.W., M.I.L.), Nuffield Department of Clinical Neurosciences, Oxford University, UK.
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Renata Faria Simm
From the Departments of Neurology (D.K.S., T.T., I.N., M.A.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Neurology (D.C., F.M.d.H.J., S.L.A.-P., R.F.S., A.M.M.L.), Faculty of Medicine, University of São Paulo, Brazil; CIEM MS Research Center (M.A.L.-P., N.T.), Federal University of Minas Gerais Medical School, Belo Horizonte, Brazil; Neuroimmunology Group (P.J.W., M.I.L.), Nuffield Department of Clinical Neurosciences, Oxford University, UK.
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Angelina Maria Martins Lino
From the Departments of Neurology (D.K.S., T.T., I.N., M.A.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Neurology (D.C., F.M.d.H.J., S.L.A.-P., R.F.S., A.M.M.L.), Faculty of Medicine, University of São Paulo, Brazil; CIEM MS Research Center (M.A.L.-P., N.T.), Federal University of Minas Gerais Medical School, Belo Horizonte, Brazil; Neuroimmunology Group (P.J.W., M.I.L.), Nuffield Department of Clinical Neurosciences, Oxford University, UK.
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Tatsuro Misu
From the Departments of Neurology (D.K.S., T.T., I.N., M.A.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Neurology (D.C., F.M.d.H.J., S.L.A.-P., R.F.S., A.M.M.L.), Faculty of Medicine, University of São Paulo, Brazil; CIEM MS Research Center (M.A.L.-P., N.T.), Federal University of Minas Gerais Medical School, Belo Horizonte, Brazil; Neuroimmunology Group (P.J.W., M.I.L.), Nuffield Department of Clinical Neurosciences, Oxford University, UK.
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Maria Isabel Leite
From the Departments of Neurology (D.K.S., T.T., I.N., M.A.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Neurology (D.C., F.M.d.H.J., S.L.A.-P., R.F.S., A.M.M.L.), Faculty of Medicine, University of São Paulo, Brazil; CIEM MS Research Center (M.A.L.-P., N.T.), Federal University of Minas Gerais Medical School, Belo Horizonte, Brazil; Neuroimmunology Group (P.J.W., M.I.L.), Nuffield Department of Clinical Neurosciences, Oxford University, UK.
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Masashi Aoki
From the Departments of Neurology (D.K.S., T.T., I.N., M.A.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Neurology (D.C., F.M.d.H.J., S.L.A.-P., R.F.S., A.M.M.L.), Faculty of Medicine, University of São Paulo, Brazil; CIEM MS Research Center (M.A.L.-P., N.T.), Federal University of Minas Gerais Medical School, Belo Horizonte, Brazil; Neuroimmunology Group (P.J.W., M.I.L.), Nuffield Department of Clinical Neurosciences, Oxford University, UK.
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Kazuo Fujihara
From the Departments of Neurology (D.K.S., T.T., I.N., M.A.) and Multiple Sclerosis Therapeutics (T.M., K.F.), Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Neurology (D.C., F.M.d.H.J., S.L.A.-P., R.F.S., A.M.M.L.), Faculty of Medicine, University of São Paulo, Brazil; CIEM MS Research Center (M.A.L.-P., N.T.), Federal University of Minas Gerais Medical School, Belo Horizonte, Brazil; Neuroimmunology Group (P.J.W., M.I.L.), Nuffield Department of Clinical Neurosciences, Oxford University, UK.
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Citation
Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders
Douglas Kazutoshi Sato, Dagoberto Callegaro, Marco Aurelio Lana-Peixoto, Patrick J. Waters, Frederico M. de Haidar Jorge, Toshiyuki Takahashi, Ichiro Nakashima, Samira Luisa Apostolos-Pereira, Natalia Talim, Renata Faria Simm, Angelina Maria Martins Lino, Tatsuro Misu, Maria Isabel Leite, Masashi Aoki, Kazuo Fujihara
Neurology Feb 2014, 82 (6) 474-481; DOI: 10.1212/WNL.0000000000000101

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Abstract

Objective: To evaluate clinical features among patients with neuromyelitis optica spectrum disorders (NMOSD) who have myelin oligodendrocyte glycoprotein (MOG) antibodies, aquaporin-4 (AQP4) antibodies, or seronegativity for both antibodies.

Methods: Sera from patients diagnosed with NMOSD in 1 of 3 centers (2 sites in Brazil and 1 site in Japan) were tested for MOG and AQP4 antibodies using cell-based assays with live transfected cells.

Results: Among the 215 patients with NMOSD, 7.4% (16/215) were positive for MOG antibodies and 64.7% (139/215) were positive for AQP4 antibodies. No patients were positive for both antibodies. Patients with MOG antibodies represented 21.1% (16/76) of the patients negative for AQP4 antibodies. Compared with patients with AQP4 antibodies or patients who were seronegative, patients with MOG antibodies were more frequently male, had a more restricted phenotype (optic nerve more than spinal cord), more frequently had bilateral simultaneous optic neuritis, more often had a single attack, had spinal cord lesions distributed in the lower portion of the spinal cord, and usually demonstrated better functional recovery after an attack.

Conclusions: Patients with NMOSD with MOG antibodies have distinct clinical features, fewer attacks, and better recovery than patients with AQP4 antibodies or patients seronegative for both antibodies.

GLOSSARY

ADEM=
acute demyelinating encephalomyelitis;
ANA=
antinuclear autoantibodies;
AQP4=
aquaporin-4;
CBA=
cell-based assay;
EDSS=
Expanded Disability Status Scale;
IgG=
immunoglobulin G;
LETM=
longitudinally extensive transverse myelitis;
MOG=
myelin oligodendrocyte glycoprotein;
MS=
multiple sclerosis;
NMO=
neuromyelitis optica;
NMOSD=
neuromyelitis optica spectrum disorders;
ON=
optic neuritis

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial, page 466

  • Supplemental data at www.neurology.org

  • Received June 9, 2013.
  • Accepted in final form September 23, 2013.
  • © 2014 American Academy of Neurology

This is an open access article distributed under the terms of the Creative Commons Attribution-Noncommercial No Derivative 3.0 License, which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.

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Letters: Rapid online correspondence

  • Response to: Anti-MOG+ ON: a mystery yet unknown
    • Douglas K. Sato, Neurologist, Tohoku University School of Medicinedouglas.sato@med.tohoku.ac.jp
    • Douglas Kazutoshi Sato, Sendai, Japan; Dagoberto Callegaro, Sao Paulo, Brazil; Marco Aurelio Lana-Peixoto, Belo Horizonte, Brazil; Ichiro Nakashima, Sendai, Japan; Kazuo Fujihara, Sendai, Japan
    Submitted May 12, 2014
  • Anti-MOG+ ON: a mystery yet unknown
    • Xueqiang Hu, Doctor, Multiple Sclerosis Center, Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen Unihuxueqiangzssy@qq.com
    • Zhifeng Mao, Zhengqi Lu, Xueqiang Hu
    Submitted March 11, 2014
  • Response to "Existence of anti-AQP4+ and anti-MOG+ neuromyelitis optica with severe recurrent optic neuritis"
    • Douglas K. Sato, Neurologist, Tohoku University School of Medicinedouglas.sato@med.tohoku.ac.jp
    • Douglas Kazutoshi Sato, Sendai, Japan; Toshiyuki Takahashi, Sendai, Japan; Patrick J. Waters, Oxford, UK; Kazuo Fujihara, Sendai, Japan
    Submitted February 04, 2014
  • Existence of anti-AQP4+ and anti-MOG+ neuromyelitis optica with severe recurrent optic neuritis
    • Takeshi Kezuka, Associate Professor, Department of Ophthalmology, Tokyo Medical Universitytkezuka@tokyo-med.ac.jp
    • Takeshi Kezuka, Tokyo, Japan; Keiko Tanaka, Ishikawa, Japan; Yoshimishi Matsunaga, Tokyo, Japan; Hiroshi Goto, Tokyo, Japan
    Submitted January 28, 2014
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