The MOG antibody non-P42 epitope is predictive of a relapsing course in MOG antibody-associated disease

Ganesha Liyanage; Benjamin P Trewin; Joseph A Lopez; Jane Andersen; Fiona Tea; Vera Merheb; Kristy Nguyen; Fiona X Z Lee; Marzena J Fabis-Pedrini; Alicia Zou; Ali Buckland; Anthony Fok; Michael H Barnett; Stephen W Reddel; Romain Marignier; Aseel El Hajj; Mastura Monif; Anneke van der Walt; Jeannette Lechner-Scott; Tomas Kalincik; Simon A Broadley; Allan G Kermode; Russell C Dale; Sudarshini Ramanathan; Fabienne Brilot; on behalf the Australasian MOGAD Study Group

doi:10.1136/jnnp-2023-332851

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The MOG antibody non-P42 epitope is predictive of a relapsing course in MOG antibody-associated disease

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The MOG antibody non-P42 epitope is predictive of a relapsing course in MOG antibody-associated disease

Ganesha Liyanage, Benjamin P Trewin, Joseph A Lopez, Jane Andersen, Fiona Tea, Vera Merheb, Kristy Nguyen, Fiona X Z Lee, Marzena J Fabis-Pedrini, Alicia Zou, …

Journal of neurology, neurosurgery and psychiatry, Vol.95(6), pp.544-553

2024

DOI: https://doi.org/10.1136/jnnp-2023-332851

PMID: 38290838

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Abstract

MULTIPLE SCLEROSIS

IMMUNOLOGY

NEUROIMMUNOLOGY

Background Myelin oligodendrocyte glycoprotein (MOG) IgG seropositivity is a prerequisite for MOG antibody-associated disease (MOGAD) diagnosis. While a significant proportion of patients experience a relapsing disease, there is currently no biomarker predictive of disease course. We aim to determine whether MOG-IgG epitopes can predict a relapsing course in MOGAD patients. Methods MOG-IgG-seropositive confirmed adult MOGAD patients were included (n=202). Serum MOG-IgG and epitope binding were determined by validated flow cytometry live cell-based assays. Associations between epitopes, disease course, clinical phenotype, Expanded Disability Status Scale and Visual Functional System Score at onset and last review were evaluated. Results Of 202 MOGAD patients, 150 (74%) patients had MOG-IgG that recognised the immunodominant proline42 (P42) epitope and 115 (57%) recognised histidine103/serine104 (H103/S104). Fifty-two (26%) patients had non-P42 MOG-IgG and showed an increased risk of a relapsing course (HR 1.7; 95% CI 1.15 to 2.60, p=0.009). Relapse-freedom was shorter in patients with non-P42 MOG-IgG (p=0.0079). Non-P42 MOG-IgG epitope status remained unchanged from onset throughout the disease course and was a strong predictor of a relapsing course in patients with unilateral optic neuritis (HR 2.7, 95% CI 1.06 to 6.98, p=0.038), with high specificity (95%, 95% CI 77% to 100%) and positive predictive value (85%, 95% CI 45% to 98%). Conclusions Non-P42 MOG-IgG predicts a relapsing course in a significant subgroup of MOGAD patients. Patients with unilateral optic neuritis, the most frequent MOGAD phenotype, can reliably be tested at onset, regardless of age and sex. Early detection and specialised management in these patients could minimise disability and improve long-term outcomes.

Details

Title: The MOG antibody non-P42 epitope is predictive of a relapsing course in MOG antibody-associated disease
Authors/Creators: Ganesha Liyanage - The University of Sydney
Benjamin P Trewin - The University of Sydney
Joseph A Lopez - Children's Hospital at Westmead
Jane Andersen - The University of Sydney
Fiona Tea - Children's Hospital at Westmead
Vera Merheb - Children's Hospital at Westmead
Kristy Nguyen - Children's Hospital at Westmead
Fiona X Z Lee - Children's Hospital at Westmead
Marzena J Fabis-Pedrini - Perron Institute for Neurological and Translational Science
Alicia Zou - Children's Hospital at Westmead
Ali Buckland - Perron Institute for Neurological and Translational Science
Anthony Fok - Monash Health
Michael H Barnett - The University of Sydney
Stephen W Reddel - The University of Sydney
Romain Marignier - Inserm
Aseel El Hajj - Inserm
Mastura Monif - Monash University
Anneke van der Walt - Monash University
Jeannette Lechner-Scott - School of Medicine and Public Health, The University of Newcastle, Callaghan, New South Wales, Australia
Tomas Kalincik - The Royal Melbourne Hospital
Simon A Broadley - Griffith University
Allan G Kermode - Murdoch University
Russell C Dale - The University of Sydney
Sudarshini Ramanathan - The University of Sydney
Fabienne Brilot - Children's Hospital at Westmead
on behalf the Australasian MOGAD Study Group
Publication Details: Journal of neurology, neurosurgery and psychiatry, Vol.95(6), pp.544-553
Publisher: BMJ Journals
Identifiers: 991005634469407891
Murdoch Affiliation: Centre for Molecular Medicine and Innovative Therapeutics; Institute for Immunology and Infectious Diseases
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.203 Neuromuscular Disorders; 1.203.147 Multiple Sclerosis
Web Of Science research areas: Clinical Neurology; Psychiatry; Surgery
ESI research areas: Clinical Medicine