• 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, Allan G Kermode, Tomas Kalincik, Simon A Broadley, Russell C Dale, Sudarshini Ramanathan, Fabienne Brilot, and on behalf the Australasian MOGAD Study Group.
• Brain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children's Hospital at Westmead, Sydney, New South Wales, Australia.
• J. Neurol. Neurosurg. Psychiatr. 2024 May 14; 95 (6): 544553544-553.

BackgroundMyelin 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.MethodsMOG-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.ResultsOf 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%).ConclusionsNon-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.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.

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