Neuroimmunological disorders occur when an “overactive” or misguided immune system starts attacking the nervous system – including the brain, optic nerves, spinal cord, neuromuscular junction, and peripheral nerves. Many neuroimmunological conditions have the potential to result in devastating disability, including blindness, paralysis, seizures, cognitive impairment, and pain. However, it is increasingly recognised that expedited diagnosis, and the institution of early and appropriate immunotherapy can result in excellent outcomes. A number of these autoantibody-mediated neurological disorders were not recognised until recent years, with many patients being undiagnosed and untreated, and accumulating disability.

The Translational Neuroimmunology Group works towards improving our understanding of underlying disease pathogenesis with a focus towards ‘precision medicine’ in neuroimmunology – both with diagnosis and therapeutics. Our clinical research focuses on defining clinical phenotypes which will enhance diagnosis of these disorders, and ensure patients do not risk misdiagnosis or delayed diagnosis. Our work has contributed to some of the earliest descriptions of the clinical and radiological hallmark features in some of these conditions, and been incorporated into international diagnostic criteria. We similarly evaluate therapeutic efficacy in patient cohorts to identify optimal therapeutic guidelines which ensure maximal neurological recovery without undue adverse effects as a result of treatment with immunosuppression. We focus on relapse prevention; and identifying laboratory, neurophysiological, and clinical biomarkers which may enable prognostication and guide therapeutic decision making. The Translational Neuroimmunology Group undertakes basic science research to better understand triggers of autoimmunity and disruption of immune tolerance, the cellular and humoural mechanisms of action of autoantibodies, and how this might be translated into refining novel therapeutic approaches. We explore cytokine profiles and innate immunity to understand how antibodies may work in conjunction with other arms of the immune system to cause disease and propagate neuronal dysfunction. We also study patients with suspected autoantibody mediated neurological disorders who are currently seronegative, to explore potential mechanisms of disease pathogenesis in these patients.

In 2013, A/Prof Ramanathan established and has since been the lead investigator of the Australasian MOGAD Study Group, a national collaboration involving over 150 clinicians from over 45 centres, evaluating over 800 children and adults with this condition. This collaborative platform has resulted in internationally influential research which has advanced the field. She co-leads an international collaboration studying 200 patients with LGI1-antibody autoimmune encephalitis to develop therapeutic guidelines.

Our team has leadership roles in national and international multicentre clinical trials in some of these disorders. We believe in the importance of cross-disciplinary innovation, and have established critical multidisciplinary collaborations with ophthalmologists, immunologists, oncologists, radiologists, and bioinformaticians in order to continue to lead international research in the field.

Some of the conditions our team studies include:

• Myelin oligodendrocyte glycoprotein antibody-associated disease
• Neuromyelitis optica spectrum disorder
• Autoimmune encephalitis
• Multiple sclerosis
• Paraneoplastic neurological disorders
• Checkpoint inhibitor associated autoimmune neurological disorders
• Autoimmune muscle disease including myasthenia gravis and myositis
• Inflammatory neuropathies
• Other inflammatory central nervous system disorders including neurosarcoidosis, CNS vasculitis, Susac syndrome, and neuro-Behcet’s disease

Our team’s work thus far has resulted in the enhanced recognition of novel treatable neurological conditions, important biological insights into the pathophysiology of these disorders, and the development of diagnostic criteria and therapeutic recommendations to improve outcomes in vulnerable patients who otherwise risk chronic disability.

The Translational Neuroimmunology group is led by Associate Professor Sudarshini Ramanathan.