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Research paper
Aquaporin-4 and myelin oligodendrocyte glycoprotein antibodies in immune-mediated optic neuritis at long-term follow-up
  1. Axel Petzold1,2,
  2. Mark Woodhall3,
  3. Z Khaleeli4,
  4. W Oliver Tobin5,
  5. Sean J Pittock5,
  6. B G Weinshenker5,
  7. Angela Vincent6,
  8. Patrick Waters7,
  9. Gordon T Plant4
  1. 1 Neuroinflammation & Neuro-ophthalmology, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery UCLH & Moorfields Eye Hospital, London, UK
  2. 2 Expertise Centre Neuro-ophthalmology, Departments of Neurology and Ophthalmology, Amsterdam UMC—Locatie VUMC, Amsterdam, Noord-Holland, The Netherlands
  3. 3 Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
  4. 4 Neurology, The National Hospital for Neurology and Neurosurgery UCLH, St. Thomas Hospital & Moorfields Eye Hospital, London, UK
  5. 5 Departments of Neurology, Immunology & Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
  6. 6 Nuffield Department of Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK
  7. 7 Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
  1. Correspondence to Dr Axel Petzold, Neuroinflammation, UCL Institute of Neurology, London WC1N 3BG, UK; a.petzold{at}ucl.ac.uk

Abstract

Objectives To re-evaluate serum samples from our 2007 cohort of patients with single-episode isolated ON (SION), recurrent isolated ON (RION), chronic relapsing inflammatory optic neuropathy (CRION), multiple sclerosis-associated ON (MSON) and neuromyelitis optica (NMO).

Methods We re-screened 103/114 patients with available serum on live cell-based assays (CBA) for aquaporin-4 (AQP4)-M23-IgG and myelin-oligodendrocyte glycoprotein (MOG)-α1-IgG. Further testing included oligoclonal bands, serum levels of glial fibrillar acidic and neurofilament proteins and S100B. We show the impact of updated serology on these patients.

Results Reanalysis of our original cohort revealed that AQP4-IgG seropositivity increased from 56% to 75% for NMO, 5% to 22% for CRION, 6% to 7% for RION, 0% to 7% for MSON and 5% to 6% for SION. MOG-IgG1 was identified in 25% of RION, 25% of CRION, 10% of SION, 0% of MSON and 0% of NMO. As a result, patients have been reclassified incorporating their autoantibody status. Presenting visual acuity was significantly worse in patients who were AQP4-IgG seropositive (p=0.034), but there was no relationship between antibody seropositivity and either ON relapse rate or visual acuity outcome.

Conclusions The number of patients with seronegative CRION and RION has decreased due to improved detection of autoantibodies over the past decade. It remains essential that the clinical phenotype guides both antibody testing and clinical management. Careful monitoring of the disease course is key when considering whether to treat with prophylactic immune suppression.

  • optic neuritis
  • CRION
  • NMO
  • aquaporin-4 (AQP4) antibody
  • myelin oligodendrocyte associated glycoprotein (MOG) antibody
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Footnotes

  • Contributors GTP, AP: study design. MW, PW, AP, AV, SJP, TWO: laboratory work. ZK, AP, MW, TWO: data collection. AP, GTP, PW, AV, BGW, SJP, TWO, GTP: data analyses and interpretation. AP: manuscript writing. all co-authors: manuscript revision.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Disclaimer The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

  • Competing interests AP, MW, ZK and GTP have no conflict of interest and nothing to disclose. This study was not funded. PW, AV and the University of Oxford hold patents for antibody assays and have received royalties. PW has received honoraria from Biogen Idec, Mereo Biopharma, Retrogenix, UBC and Euroimmun AG; travel grants from the Guthy-Jackson Charitable Foundation; and research funding from Euroimmun AG. BGW receives royalties from RSR Ltd, Oxford University, Hospices Civil de Lyon, and MVZ Labor PD Dr. Volkmann und Kollegen GbR for a patent of NMO-IgG as a diagnostic test for NMO and related disorders. He serves as a member of an adjudication committee for clinical trials in NMO being conducted by MedImmune and Alexion pharmaceutical companies. He was a consultant for Caladrius Biosciences, Brainstorm Therapeutics, Roivant Sciences and Chugai Pharma regarding potential clinical trials for NMO. He serves as a member of a data safety monitoring committee for clinical trials conducted by Novartis. SJP has intellectual property associated with the discovery of NMO-IgG, which has been licensed to a commercial entity. The NMO-IgG test is offered on a service basis by Mayo Collaborative Service Inc, an agency of Mayo Foundation. SJP is a named inventor on patents (12/678,350 filed 2010 and 12/573,942 filed 2008) that relate to functional AQP4/NMO-IgG assays and NMO-IgG as a cancer marker and receives research support from Alexion Pharmaceuticals, Inc, Medimmune LLC and Grifols. He has provided consultation to Alexion Pharmaceutical, MedImmune LLC and Chugai Pharma, but has received no personal fees or compensation for these consulting activities. All compensation for consulting activities is paid directly to Mayo Clinic.

  • Patient consent for publication Not required.

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

  • Data sharing statement Data are available upon reasonable request.

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