019 – Characterisation of the human MOG antibody response improves the diagnosis of MOG antibody-associated demyelination

Electronic Poster | Session 2

019 – Characterisation of the human MOG antibody response improves the diagnosis of MOG antibody-associated demyelination

Fiona Tea (1, 2) – Joseph A. Lopez (1, 2) – Sudarshini Ramanathan (1, 2) – Vera Merheb (1) – Fiona X. Z. Lee (1) – Alicia Zou (1, 2) – Deepti Pilli (1, 2) – Ellis Patrick (3, 4) – Anneke van der Walt (5) – Mastura Monif (5) – Esther M. Tantsis (1, 2) – Eppie M. Yiu (6) – Steve Vucic (7) – Andrew P. D. Henderson (7) – Anthony Fok (8) – Clare L. Fraser (9) – Jeanette Lechner-Scott (10) – Stephen W. Reddel (11, 12) – Simon Broadley (13) – Michael H. Barnett (11) – David A. Brown (14) – Jan D. Lunemann (15) – Russell C. Dale (1, 2, 11) – Fabienne Brilot (1, 2, 3, 11, *) – the Australasian and New Zealand MOG Study Group.
Brain Autoimmunity Group, Kids Neuroscience Centre, Kids Research at the Children’s Hospital at Westmead, Sydney, Australia (1) – Discipline of Child and Adolescent Health, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia (2) – Discipline of Applied Medical Science, The University of Sydney, Sydney, Australia (3) – School of Mathematics and Statistics, The University of Sydney, Sydney, Australia (4) – Department of Neurosciences, Central Clinical School, Monash University, Melbourne, Australia (5) – Department of Neurology, Royal Children’s Hospital and Neurosciences Research, Murdoch Children’s Research Institute and Department of Paediatrics, The University of Melbourne, Melbourne, Australia (6) – Department of Neurology, Westmead Hospital, Sydney, Australia (7) – Department of Neurology, Monash Health, Melbourne, Australia (8) – Save Sight Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia (9) – Hunter Medical Research Institute, Faculty of Medicine and Public Health, The University of Newcastle, Department of Neurology, John Hunter Hospital, Newcastle, Australia (10) – Brain and Mind Centre, The University of Sydney, Sydney, Australia (11) – Department of Neurology, Concord Repatriation General Hospital, Sydney, Australia (12) – Department of Neurology, Gold Coast University Hospital, School of Medicine, Griffith University, Gold Coast, Australia (13) – New South Wales Health Pathology, Institute of Clinical Pathology and Medical Research, and Westmead Institute for Medical Research, The University of Sydney, Sydney, Australia (14) – Department of Neurology, University of Münster, Münster, Germany (15)


Background and Aim: Over recent years, autoantibodies targeting myelin oligodendrocyte glycoprotein (MOG Ab) have been associated with monophasic and relapsing central nervous system demyelination involving the optic nerves, spinal cord, and brain. While the clinical relevance of MOG Ab detection is becoming increasingly clear, an in-depth characterization of the human MOG Ab response is required to answer key challenges in patient diagnosis, treatment, and prognosis. Herein, we explore the epitope and binding sensitivity of MOG Ab to native and fixed MOG in a cohort of 139 children and 148 adults. Results: By flow cytometry, we identified a major conformational epitope at Proline42. Longitudinal analysis in patients spanning up to 5 years showed stable epitope immunoreactivity. Interestingly, adults with a relapsing course have a reduced immunoreactivity to Proline42. Higher titers of MOG Ab were observed in more severe phenotypes and during active disease, supporting the pathogenic role of MOG Ab. We then performed flow cytometry on live and fixed cells, and commercial assays, to characterize the MOG Ab binding sensitivity. A significant loss of MOG Ab seropositivity was observed upon conformational changes to MOG and in commercial assays. Although the specificity of detection remained high between assays, the sensitivity of the flow cytometry live assay was far greater than the fixed and commercial biochip assay. Conclusion: Reduced immunoreactivity to Proline42 in relapsing adults could be harnessed to predict patient relapse. We shed critical light on the binding sensitivity of the human MOG antibody response. Loss of seropositivity in fixed and commercial assays impacts patient diagnosis and prompts careful consideration of the conformational state of autoantigens when detecting disease-relevant autoantibodies.