The clinical relevance of MOG antibody testing in cerebrospinal fluid

Molly Reynolds^{1

2}, Irene Tan³, Kristy Nguyen⁴, Vera Merheb⁴, Fiona X Z Lee⁴, Benjamin P Trewin^{1

5}, Magdalena Lerch¹, Snehal Shah⁶, Nigel Wolfe⁷, Katherine Buzzard⁸, Jeannette Lechner-Scott^{9

10}, Marzena Fabis-Pedrini^{11

12}, Anthony Fok^{13

14}, Nevin John^{13

14}, Chris Kneebone¹⁵, Con Yiannikas¹⁶, David A Brown^{17

18}, Allan G Kermode^{11

12}, Stephen Reddel^{2

5}, Russell C Dale^{5

19

20}, Fabienne Brilot^#^{4

21}, Sudarshini Ramanathan^#^{1

2

5}; Australasian MOGAD Study Group

Collaborators, Affiliations

Collaborators

Australasian MOGAD Study Group:
Robert Adam, Jane Andersen, Ian Andrews, Jayne Antony, Patrick Aouad, Monica Badve, Michael H Barnett, Joshua Barton, Heidi Beadnall, Stefan Blum, Michael Boggild, Fabienne Brilot, Simon Broadley, David A Brown, Jim Burrow, Helmut Butzkueven, Katherine Buzzard, Ann Bye, Anita Cairns, Sophie Calvert, Fiona Chan, Shabeed Chelakkadan, Melissa Chu, Damian R Clark, Isabella Cotter, Russell C Dale, Fionna Dela Cruz, Marzena J Fabis-Pedrini, Deborah Field, Anthony Fok, Clare L Fraser, Victor S C Fung, Justin Garber, Serge Geara, Deepak Gill, Sachin Gupta, Todd A Hardy, Simon Hawke, Andrew P D Henderson, Niroshan Jeyakumar, Nevin A John, Dean L Jones, Hannah F Jones, Tomas Kalincik, Allan Kermode, Matthew Kiernan, Trevor Kilpatrick, Chris Kneebone, Andrew J Kornberg, Mitchell Lawlor, Jeannette Lechner-Scott, Fiona X Z Lee, Magdalena Lerch, Richard J Leventer, Vivien Li, Simon Ling, Ganesha Liyanage, Joseph A Lopez, Kit Kwan Margaret Ma, Stephen Malone, Mark P Marriot, Pamela McCombe, Alan McDougall, Manoj P Menezes, Vera Merheb, Christina Miteff, Mastura Monif, Gopinath Musuwadi Subramanian, Kristy Nguyen, Ai-Lan Nguyen, Gina O'Grady, John O'Neill, Robert Ouvrier, Mark Paine, John Parratt, Sekhar Pillai, Jane Prosser, Jessica Qiu, Sudarshini Ramanathan, Stephen Reddel, Molly Reynolds, Sean Ds Riminton, Izanne Roos, Jennifer Sandbach, Ingrid E Scheffer, Snehal Shah, Ubaid Shah, Neil Shuey, Adriane Sinclair, Pakeeran Siriratnam, Mark Slee, Claire G Spooner, Ian Sutton, Sanjay Swaminathan, Esther Tantsis, James Thomas, Terrence Thomas, Julia Thompson, Benjamin P Trewin, Christopher Troedson, Anneke Van der Walt, Steve Vucic, Justine Wang, Tyson Ware, Richard Webster, Ming Wei Lin, Owen White, Nigel Wolfe, Wei Yeh, Con Yiannikas, Eppie M Yiu, Michael Zhong

Affiliations

¹ Translational Neuroimmunology Group, Kids Neuroscience Centre, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
² Department of Neurology, Concord Hospital, Sydney, Australia.
³ Department of Radiology, Concord Hospital, Sydney, Australia.
⁴ Brain Autoimmunity Group, Kids Neuroscience Centre, Children's Hospital at Westmead, Sydney, Australia.
⁵ Sydney Medical School and Brain and Mind Centre, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
⁶ Department of Neurology, Perth Children's Hospital, University of Western Australia, Perth, Australia.
⁷ Department of Neurology, Blacktown Hospital, Sydney, Australia.
⁸ MS and Neuroimmunology Service, Royal Melbourne Hospital, Melbourne, Australia.
⁹ Hunter Medical Research Institute, Faculty of Medicine and Public Health, University of Newcastle, Newcastle, Australia.
¹⁰ Department of Neurology, John Hunter Hospital, Newcastle, Australia.
¹¹ The Perron Institute for Neurological and Translational Science, University of Western Australia, Perth, Australia.
¹² The Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth, Australia.
¹³ Department of Neuroscience, Monash Health, Melbourne, Australia.
¹⁴ Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia.
¹⁵ Department of Neurology, Royal Adelaide Hospital, Adelaide, Australia.
¹⁶ Inner West Neurology, Burwood, Sydney, Australia.
¹⁷ ICPMR and Department of Immunopathology, NSW Health Pathology, Westmead Hospital, Westmead, Sydney, Australia.
¹⁸ Clinical Immunology and Allergy Research, Westmead Institute for Medical Research, Westmead, Sydney, Australia.
¹⁹ Clinical Neuroimmunology Group, Kids Neuroscience Centre, Children's Hospital at Westmead, Sydney, Australia.
²⁰ TY Nelson Department of Neurology, Children's Hospital at Westmead, Sydney, Australia.
²¹ School of Medical Science and Brain and Mind Centre, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.

^# Contributed equally.

PMID: 39073255
PMCID: PMC11537122
DOI: 10.1002/acn3.52163

The clinical relevance of MOG antibody testing in cerebrospinal fluid

Molly Reynolds et al. Ann Clin Transl Neurol. 2024 Sep.

. 2024 Sep;11(9):2514-2519.

doi: 10.1002/acn3.52163. Epub 2024 Jul 28.

Authors

Collaborators

Australasian MOGAD Study Group:
Robert Adam, Jane Andersen, Ian Andrews, Jayne Antony, Patrick Aouad, Monica Badve, Michael H Barnett, Joshua Barton, Heidi Beadnall, Stefan Blum, Michael Boggild, Fabienne Brilot, Simon Broadley, David A Brown, Jim Burrow, Helmut Butzkueven, Katherine Buzzard, Ann Bye, Anita Cairns, Sophie Calvert, Fiona Chan, Shabeed Chelakkadan, Melissa Chu, Damian R Clark, Isabella Cotter, Russell C Dale, Fionna Dela Cruz, Marzena J Fabis-Pedrini, Deborah Field, Anthony Fok, Clare L Fraser, Victor S C Fung, Justin Garber, Serge Geara, Deepak Gill, Sachin Gupta, Todd A Hardy, Simon Hawke, Andrew P D Henderson, Niroshan Jeyakumar, Nevin A John, Dean L Jones, Hannah F Jones, Tomas Kalincik, Allan Kermode, Matthew Kiernan, Trevor Kilpatrick, Chris Kneebone, Andrew J Kornberg, Mitchell Lawlor, Jeannette Lechner-Scott, Fiona X Z Lee, Magdalena Lerch, Richard J Leventer, Vivien Li, Simon Ling, Ganesha Liyanage, Joseph A Lopez, Kit Kwan Margaret Ma, Stephen Malone, Mark P Marriot, Pamela McCombe, Alan McDougall, Manoj P Menezes, Vera Merheb, Christina Miteff, Mastura Monif, Gopinath Musuwadi Subramanian, Kristy Nguyen, Ai-Lan Nguyen, Gina O'Grady, John O'Neill, Robert Ouvrier, Mark Paine, John Parratt, Sekhar Pillai, Jane Prosser, Jessica Qiu, Sudarshini Ramanathan, Stephen Reddel, Molly Reynolds, Sean Ds Riminton, Izanne Roos, Jennifer Sandbach, Ingrid E Scheffer, Snehal Shah, Ubaid Shah, Neil Shuey, Adriane Sinclair, Pakeeran Siriratnam, Mark Slee, Claire G Spooner, Ian Sutton, Sanjay Swaminathan, Esther Tantsis, James Thomas, Terrence Thomas, Julia Thompson, Benjamin P Trewin, Christopher Troedson, Anneke Van der Walt, Steve Vucic, Justine Wang, Tyson Ware, Richard Webster, Ming Wei Lin, Owen White, Nigel Wolfe, Wei Yeh, Con Yiannikas, Eppie M Yiu, Michael Zhong

Affiliations

¹ Translational Neuroimmunology Group, Kids Neuroscience Centre, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
² Department of Neurology, Concord Hospital, Sydney, Australia.
³ Department of Radiology, Concord Hospital, Sydney, Australia.
⁴ Brain Autoimmunity Group, Kids Neuroscience Centre, Children's Hospital at Westmead, Sydney, Australia.
⁵ Sydney Medical School and Brain and Mind Centre, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
⁶ Department of Neurology, Perth Children's Hospital, University of Western Australia, Perth, Australia.
⁷ Department of Neurology, Blacktown Hospital, Sydney, Australia.
⁸ MS and Neuroimmunology Service, Royal Melbourne Hospital, Melbourne, Australia.
⁹ Hunter Medical Research Institute, Faculty of Medicine and Public Health, University of Newcastle, Newcastle, Australia.
¹⁰ Department of Neurology, John Hunter Hospital, Newcastle, Australia.
¹¹ The Perron Institute for Neurological and Translational Science, University of Western Australia, Perth, Australia.
¹² The Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth, Australia.
¹³ Department of Neuroscience, Monash Health, Melbourne, Australia.
¹⁴ Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia.
¹⁵ Department of Neurology, Royal Adelaide Hospital, Adelaide, Australia.
¹⁶ Inner West Neurology, Burwood, Sydney, Australia.
¹⁷ ICPMR and Department of Immunopathology, NSW Health Pathology, Westmead Hospital, Westmead, Sydney, Australia.
¹⁸ Clinical Immunology and Allergy Research, Westmead Institute for Medical Research, Westmead, Sydney, Australia.
¹⁹ Clinical Neuroimmunology Group, Kids Neuroscience Centre, Children's Hospital at Westmead, Sydney, Australia.
²⁰ TY Nelson Department of Neurology, Children's Hospital at Westmead, Sydney, Australia.
²¹ School of Medical Science and Brain and Mind Centre, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.

^# Contributed equally.

PMID: 39073255
PMCID: PMC11537122
DOI: 10.1002/acn3.52163

Abstract

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is diagnosed by serum MOG-immunoglobulin G (MOG-IgG) in association with typical demyelination. 111/1127 patients with paired CSF/serum samples were seropositive for MOG-IgG. Only 7/1016 (0.7%) seronegative patients had CSF-restricted MOG-IgG. While 3/7 patients had longitudinally extensive transverse myelitis, four had a confirmed alternate diagnosis (three multiple sclerosis, one CNS vasculitis). In a national referral setting, CSF-restricted MOG-IgG had a low sensitivity (2.63%, 95%CI 0.55-7.50%) and low positive predictive value (1.97%, 95%CI 0.45-8.13%). We strongly recommend serum as the preferred diagnostic biospecimen, and urge caution in the interpretation of CSF-restricted MOG-IgG in patients without clinico-radiological features consistent with MOGAD.

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Conflict of interest statement

MR has received travel support from Alexion and Roche and honoraria for an invited educational session from Novartis. BT receives a University of Sydney postgraduate scholarship and a stipend from CIA Ramanathan's Royal Australasian College of Physicians Research Establishment Fellowship. JL‐S received travel compensation from Biogen, Merck, and Novartis; has been involved in clinical trials with Biogen, Novartis, and Roche; her institution has received honoraria for talks and advisory board service from Biogen, Merck, Novartis, and Roche. She is on the board of directors for MSPlus. MF‐P has received a research grant from MS Australia and travel compensation from Merck. AGK has in recent times received speaker honoraria and Scientific Advisory Board fees from Bayer, BioCSL, Biogen‐Idec, Lgpharma, Merck, Novartis, Roche, Sanofi‐Aventis, Sanofi‐Genzyme, Teva, NeuroScientific Biopharmaceuticals, Innate Immunotherapeutics, and Mitsubishi Tanabe Pharma. His work has received grant funding from the Eyewall Foundation, Trish MS Foundation, MS Australia, MS Western Australia, the MS Base Foundation, the National Health and Medical Research Council of Australia, and the National Multiple Sclerosis Society, USA. He is an investigator in clinical trials sponsored by Biogen Idec and Novartis. NAJ is a principal investigator on commercial MS trials sponsored by Roche, Novartis, and Biogen. He has received speakers honoraria from Merck and travel congress sponsorship from Novartis. SWR has received travel support, honoraria, trial payments, research and clinical support to the neurology department or academic projects from NHMRC, MRFF, NBA, Myasthenia Alliance Australia, Lambert Initiative, Beeren foundation, anonymous donors; and from pharmaceutical/biological companies: Alexion, Biogen, CSL, Genzyme, Grifols, Merck, Novartis, Roche, Sandoz, Sanofi, and UCB. He is Co‐founder/shareholder of RxPx health, National IVIG Governance Advisory Council & Specialist Working Group Australia (Neurology) (paid), Australian Medical Services Advisory Committee ad hoc sub‐committee on IVIG (paid), Australian Technical Advisory Group on Immunisation Varicella Zoster working party (unpaid), Medical advisor (unpaid) to various patient and advocacy groups. Funds over the last 5 years including but not limited to travel support, honoraria, trial payments, research and clinical support to the neurology department or academic projects from: NHMRC, MRFF, NBA, Myasthenia Alliance Australia, Lambert Initiative, Beeren foundation, and anonymous donors; and from pharmaceutical/biological companies: Alexion, Biogen, CSL, Genzyme, Grifols, Merck, Novartis, Roche, Sandoz, Sanofi, and UCB. RCD has received research funding from the Star Scientific Foundation, The Trish Multiple Sclerosis Research Foundation, Multiple Sclerosis Research Australia, the Petre Foundation, and the NHMRC (Australia; Investigator Grant). He has also received honoraria from Biogen Idec as an invited speaker, and is on the IDMC for a Roche RCT in pediatric MS. He is on the medical advisory board (nonremunerated position). FB has received research funding from NSW Health, MS Australia, the NHMRC (Australia), the Medical Research Future Fund (Australia), The MOG Project (Apollo Grant) and Novartis. She was on an advisory board for Novartis and Merck, and has been an invited speaker for Biogen, Novartis, and Limbic Neurology. She is on the medical advisory board (nonremunerated positions) of The MOG Project and the Sumaira Foundation. SR has received research funding from the National Health and Medical Research Council (NHMRC, Australia), the Petre Foundation, the Brain Foundation, the Royal Australasian College of Physicians, and the University of Sydney. She is supported by an NHMRC Investigator Grant (GNT2008339). She serves as a consultant on an advisory board for UCB and Limbic Neurology, and has been an invited speaker for educational/research sessions coordinated by Biogen, Alexion, Novartis, Excemed, and Limbic Neurology. She is on the medical advisory board (nonremunerated positions) of The MOG Project and the Sumaira Foundation. All other authors have no relevant disclosures to report.

Figures

**Figure 1**
MRI features of non‐MOGAD diagnoses. (A) Perpendicular, periventricular T2 FLAIR hyperintensity (Dawson's Fingers, arrow) pathognomonic for multiple sclerosis. (B) T1 postgadolinium enhancement in an incomplete ring pattern (arrow) in the left parietal lobe consistent with demyelination in MS. (C) Bilateral periventricular and right cortical parietal lesions demonstrating diffusion restriction of varying intensity suggests recent established infarctions of varying acuity. (D and E) 3 months after (C) demonstrates right parietal lobe cortical and subcortical T2 hyperintensity with adjacent gyriform hemosiderin deposition consistent with interval established infarct and adjacent blood product deposition, in combination, suggestive of vasculitis.

See this image and copyright information in PMC

References

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The clinical relevance of MOG antibody testing in cerebrospinal fluid

Collaborators

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The clinical relevance of MOG antibody testing in cerebrospinal fluid

Authors

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Abstract

Conflict of interest statement

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