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Clinical spectrum associated with MOG autoimmunity in adults: significance of sharing rodent MOG epitopes

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Abstract

The aim of this study was to report the clinical spectrum associated with antibodies to myelin oligodendrocyte glycoprotein (MOG) in adult patients, and to assess whether phenotypic variants are dependent on recognition of rodent MOG epitopes. We retrospectively analyzed the features, course and outcome of 56 patients whose samples were investigated by brain tissue immunohistochemistry and cell-based assays using human and rodent MOG. The median age at symptom onset was 37 years (range 18–70); 35 patients (63 %) were female. After a median follow-up of 43 months (range 4–554), only 14 patients (25 %) developed a neuromyelitis optica spectrum disorder (NMOSD), 27 patients (47 %) retained the initial diagnosis of isolated optic neuritis, 7 (12 %) of longitudinally extensive transverse myelitis, and 2 (4 %) of acute disseminated encephalomyelitis; 6 patients (11 %) developed atypical demyelinating syndromes (4 had relapsing episodes of short myelitis lesions which in one occurred with optic neuritis; 1 had relapsing brainstem symptoms, and 1 relapsing demyelinating encephalomyelitis). The course was frequently associated with relapses (71 %) and good outcome. Twenty-seven patients (49 %) had antibodies that recognized rodent MOG epitopes, and 9 of them (16 %) showed a myelin staining pattern in rodent tissue. Only the myelin staining pattern was linked to NMOSD (p = 0.005). In conclusion, MOG autoimmunity in adult patients associates with a clinical spectrum wider than the one expected for patients with suspected NMOSD and overall good outcome. Antibodies to rodent MOG epitopes do not associate with any phenotypic variant.

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Acknowledgments

This work was supported in part by Red Española de Esclerosis Múltiple, Instituto de Salud Carlos III, Spain (RD12/0032/0002, AS; CM14/00081, TA); Marató de TV3 (20141830, FG) and Dodot Procter & Gamble research Grant sponsored by Asociación Española de Pediatría (AEP) (DN040579, TA). PP and MR were supported by a research Grant from the Fonds zur Förderung der wissenschaftlichen Forschung, Austria (FWF graduate program W1206 SPIN). JD was supported in part by NIH RO1NS077851, Instituto Carlos III/FEDER (FIS 14/00203), and CIBERER, and Fundació CELLEX. The authors thank Eva Caballero and Mercè Alba for their excellent technical support, and the neurologists of the Spanish Group of Neuromyelitis optica and Red Española de Esclerosis Múltiple. We are thankful to Dr. Ellen Gelpi from the Neurological Tissue Bank of the IDIBAPS Biobank for her assistance in figure composition.

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Authors and Affiliations

  1. Service of Neurology, Department of Neurology, Hospital Clínic, University of Barcelona, Villarroel 170, 08036, Barcelona, Spain

    Maria Sepúlveda, Nuria Sola-Valls, Helena Ariño, Yolanda Blanco, Francesc Graus & Albert Saiz

  2. Neuroimmunology Program, Institut d´Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Maria Sepúlveda, Thaís Armangue, Eugenia Martinez-Hernandez, Nuria Sola-Valls, Lidia Sabater, Helena Ariño, Yolanda Blanco, Josep Dalmau, Francesc Graus & Albert Saiz

  3. Neuroimmunology Unit, Department of Child Neurology, Sant Joan de Déu Hospital, University of Barcelona, Esplugues de Llobregat, Barcelona, Spain

    Thaís Armangue

  4. Servei de Neurologia-Neuroimmunologia, Centre d´Esclerosi Múltiple de Catalunya (Cemcat), Vall d´Hebron Institut de Recerca, Hospital Universitari Vall d´Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain

    Georgina Arrambide & Xavier Montalban

  5. Neurology Department, Hospital Clínico Universitario de Valladolid, Valladolid, Spain

    Nieves Téllez

  6. Department of Neurology, Hospital Álvaro Cunqueiro, Vigo, Spain

    Luciana Midaglia

  7. Clinical Department of Neurology, Innsbruck Medical University, Innsbruck, Austria

    Patrick Peschl & Markus Reindl

  8. Magnetic Resonance Unit, Department of Radiology (IDI), Hospital Universitari Vall d´Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain

    Alex Rovira

  9. Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA

    Josep Dalmau

  10. Institució Catalana de Recerca i Estudos Avançats (ICREA), Barcelona, Spain

    Josep Dalmau

Authors
  1. Maria Sepúlveda
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  2. Thaís Armangue
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  3. Eugenia Martinez-Hernandez
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  4. Georgina Arrambide
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  5. Nuria Sola-Valls
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  6. Lidia Sabater
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  8. Luciana Midaglia
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  9. Helena Ariño
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  10. Patrick Peschl
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  11. Markus Reindl
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  12. Alex Rovira
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  13. Xavier Montalban
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  14. Yolanda Blanco
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  15. Josep Dalmau
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  17. Albert Saiz
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Corresponding author

Correspondence to Albert Saiz.

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Conflicts of interest

Sepúlveda, Armangue, Martinez-Hernandez, Sola-Valls, Sabater, Midaglia, Ariño, Peschl, and Blanco declare that there is no conflict of interest. Arrambide has received compensation for consulting services from Biogen Idec and research support from Novartis; Téllez has received compensation for consulting services, speaker honoraria, and travel expenses from Bayer-Schering, Merck-Serono, Biogen Idec, Sanofi, Teva Pharmaceutical Industries Ltd, and Novartis; Reindl has a common research project on MOG antibodies with Euroimmun funded by the Austrian Research Promotion Agency (FFG); Rovira serves on the scientific advisory boards for Biogen Idec, Novartis, Genzyme, and OLEA Medical, and on the editorial board of the American Journal of Neuroradiology and Neuroradiology, has received speaker honoraria from Bayer, Genzyme, Sanofi-Aventis, Bracco, Merck-Serono, Teva Pharmaceutical Industries Ltd, OLEA Medical, Stendhal, Novartis and Biogen Idec, and has research agreements with Siemens AG; Montalban has received speaker honoraria and travel expenses for scientific meetings, has been a steering committee member of clinical trials, or participated in advisory boards of clinical trials in the past with Bayer-Schering Pharma, Biogen Idec, EMD Merck-Serono, Genentech, Genzyme, Novartis, Sanofi-Aventis, Teva Pharmaceuticals, and Almirall; Dalmau has a research grant from Euroimmun and receives royalties from patents for the use of Ma2 and NMDAR as autoantibody tests; Graus receives royalties from licensing fees to Euroimmun for the use of IgLON5 as a diagnostic test; Saiz has received compensation for consulting services and speaker honoraria from Bayer-Schering, Merck-Serono, Biogen Idec, Sanofi-Aventis, Teva Pharmaceutical Industries Ltd, and Novartis.

Ethical standards

This clinical study was approved by the Ethic Committee of the Hospital Clinic of Barcelona. Samples are deposited in the registered biobank of Institut d´Investigació Biomèdica August Pi i Sunyer (IDIBAPS). Informed consent for storage and use of these samples for research purposes was obtained from all patients. The study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Sepúlveda, M., Armangue, T., Martinez-Hernandez, E. et al. Clinical spectrum associated with MOG autoimmunity in adults: significance of sharing rodent MOG epitopes. J Neurol 263, 1349–1360 (2016). https://doi.org/10.1007/s00415-016-8147-7

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  • DOI: https://doi.org/10.1007/s00415-016-8147-7

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