Understanding the role of brain auto-antibodies in MS

Associate Professor Fabienne Brilot

University of Sydney, NSW

| Better treatments | Immunology | Incubator | 2020 | Investigator Led Research |
SUPPORT PROJECTS WITH THIS RESEARCH FOCUS

Summary

In addition to MS there are other diseases in which the immune system attacks and damages the optic nerve, brain and spinal cord. It can be challenging when diagnosing these diseases to correctly differentiate between these and MS. It is important to do so, because they have different treatment options. One way to help differentiate these diseases is by measuring “autoantibodies” in the blood. Autoantibodies are antibodies that mistakenly attack the human body instead of foreign invaders.

Autoantibodies that mistakenly attack a protein in the brain call myelin oligodendrocyte glycoprotein (MOG) are a sign that an individual is likely to have Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), which has different treatment options to MS.

However an unusual group of MS patients also test positive for MOG antibodies (in certain specialised tests), and this project will find out whether they might be affected by both MS and MOG antibody-associated disorder, and whether their MOG antibodies are different.

This project will help recognition of these patients, their diagnosis, and their treatment.

Progress to Date

Myelin oligodendrocyte glycoprotein (MOG) antibodies are used in diagnosis to discriminate certain demyelinating disorders of the optic nerve, brain, and spinal cord from MS. Once diagnosed, people who are positive for MOG antibody are treated differently to people with MS. This includes disease modifying treatment for people with MS and immunosuppression for people who are positive for MOG antibody, with early treatment improving clinical outcomes.

Associate Professor Brilot-Turville and her team have found that there is a small group of people with MS who test positive for MOG antibody, but they are not formally diagnosed with MOGAD according to the first international MOGAD diagnostic criteria. The amount and response of MOG antibodies detected in people with MS was similar to people with MOGAD. However, the amount of high affinity MOG antibodies was higher in people with MS compared to people with MOGAD tested in this study and previous studies.

Associate Professor Brilot-Turville and her team have also determined the range of the MOG antibody assay used to detect MOG antibody levels, which will assist in clinical diagnosis of people with MS. This work will hopefully improve accurate early diagnosis of MOG antibody positive MS patients and define the clinical spectrum of MOGAD.

Publications

Lopez JA, Houston SD, Tea F, Merheb V, Lee FXZ, Smith S, McDonald D, Zou A, Liyanage G, Pilli D, Denkova M, Lechner-Scott J, van der Walt A, Barnett MH, Reddel SW, Broadley S, Ramanathan S, Dale RC, Brown DA, Brilot F. Validation of a Flow Cytometry Live Cell-Based Assay to Detect Myelin Oligodendrocyte Glycoprotein Antibodies for Clinical Diagnostics. J Appl Lab Med. 2022 Jan 5;7(1):12-25. doi: 10.1093/jalm/jfab101. PMID: 34718586.

Lopez JA, Denkova M, Ramanathan S, Dale RC, Brilot F. Pathogenesis of autoimmune demyelination: from multiple sclerosis to neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein antibody-associated disease. Clin Transl Immunology. 2021 Jul 26;10(7):e1316. doi: 10.1002/cti2.1316. PMID: 34336206; PMCID: PMC8312887.

Marignier R, Hacohen Y, Cobo-Calvo A, Pröbstel AK, Aktas O, Alexopoulos H, Amato MP, Asgari N, Banwell B, Bennett J, Brilot F, Capobianco M, Chitnis T, Ciccarelli O, Deiva K, De Sèze J, Fujihara K, Jacob A, Kim HJ, Kleiter I, Lassmann H, Leite MI, Linington C, Meinl E, Palace J, Paul F, Petzold A, Pittock S, Reindl M, Sato DK, Selmaj K, Siva A, Stankoff B, Tintore M, Traboulsee A, Waters P, Waubant E, Weinshenker B, Derfuss T, Vukusic S, Hemmer B. Myelin-oligodendrocyte glycoprotein antibody-associated disease. Lancet Neurol. 2021 Sep;20(9):762-772. doi: 10.1016/S1474-4422(21)00218-0. Erratum in: Lancet Neurol. 2021 Oct;20(10):e6. Erratum in: Lancet Neurol. 2022 Jan;21(1):e1. PMID: 34418402.

Updated: 31 March 2022

Updated: 21 January, 2020

Stages of the research process

Fundamental laboratory
Research

Laboratory research that investigates scientific theories behind the possible causes, disease progression, ways to diagnose and better treat MS.

Lab to clinic timeline: 10+ years
Translational
Research

Research that builds on fundamental scientific research to develop new therapies, medical procedures or diagnostics and advances it closer to the clinic.

Lab to clinic timeline: 5+ years
Clinical Studies
and Clinical Trials

Clinical research is the culmination of fundamental and translational research turning those research discoveries into treatments and interventions for people with MS.

Lab to clinic timeline: 1-5 years

Grant Awarded

  • Incubator Grant

Total Funding

  • $25,000

Duration

  • 1 year

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Understanding the role of brain auto-antibodies in MS