TY - JOUR
T1 - The MOG antibody non-P42 epitope is predictive of a relapsing course in MOG antibody-Associated disease
AU - Liyanage, Ganesha
AU - Trewin, Benjamin P.
AU - Lopez, Joseph A.
AU - Andersen, Jane
AU - Tea, Fiona
AU - Merheb, Vera
AU - Nguyen, Kristy
AU - Lee, Fiona X.Z.
AU - Fabis-Pedrini, Marzena J.
AU - Zou, Alicia
AU - Buckland, Ali
AU - Fok, Anthony
AU - Barnett, Michael H.
AU - Reddel, Stephen W.
AU - Marignier, Romain
AU - El Hajj, Aseel
AU - Monif, Mastura
AU - Van Der Walt, Anneke
AU - Lechner-Scott, Jeannette
AU - Kermode, Allan G.
AU - Kalincik, Tomas
AU - Broadley, Simon A.
AU - Dale, Russell C.
AU - Ramanathan, Sudarshini
AU - Brilot, Fabienne
AU - on behalf the Australasian MOGAD Study Group
N1 - Funding Information:
We thank all the patients and family members who participated in this study. We thank The MOG Project and The Sumaira Foundation for their immense work in patient education and advocacy. We thank Dr Maggie Wang and Dr Suat Dervish for our use of the Flow Cytometry Core Facility of the Westmead Research Hub (Australia) supported by the Cancer Institute New South Wales, the National Health and Medical Research Council, and the Ian Potter Foundation. We thank the Sydney Informatics Hub (The University of Sydney) for their assistance with statistical analyses.
Funding Information:
This work was supported by research and investigators grants from the National Health Medical Research Council (Australia, FB GNT2016841, SR GNT2008339, RCD GNT1193648, AVDW GNT1196380), MS Australia (20-0000000025) and Sydney Research Excellence Initiative 2020 (The University of Sydney, Australia), Apollo Grant (The MOG project, USA). GL and BPT receive a postgraduate scholarship from the Australian government (Research Training Program) and the University of Sydney.
Publisher Copyright:
© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.
PY - 2024/6
Y1 - 2024/6
N2 - 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.
AB - 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.
KW - IMMUNOLOGY
KW - MULTIPLE SCLEROSIS
KW - NEUROIMMUNOLOGY
UR - http://www.scopus.com/inward/record.url?scp=85184491982&partnerID=8YFLogxK
U2 - 10.1136/jnnp-2023-332851
DO - 10.1136/jnnp-2023-332851
M3 - Article
C2 - 38290838
AN - SCOPUS:85184491982
SN - 0022-3050
VL - 95
SP - 544
EP - 553
JO - Journal of Neurology, Neurosurgery and Psychiatry
JF - Journal of Neurology, Neurosurgery and Psychiatry
IS - 6
ER -
