Colour image of nerves in the brain

Neuroimmunology

Developing new ways to diagnose and treat neurological disorders
Our neuroimmunology team examines the link between dysregulations of the immune system and its impact on neurological disorders such as multiple sclerosis and dementia, as well as psychiatric diseases including schizophrenia.

About our research

Autoantibodies are antibodies directed against the body’s own tissues or organs, present in many autoimmune diseases. In addition, it is increasingly recognised that autoantibodies are found in a number of other childhood and adult nervous system disorders including neurodevelopmental disorders like autism, neurodegenerative diseases such as dementia, and psychiatric disorders including schizophrenia. Their presence in these disorders provides us with an unprecedented opportunity to develop new ways of diagnosing these diseases as well as monitor their progression and assess the effectiveness of different treatments.

The Neuroimmunology team is at the forefront of this research, focused on identifying and investigating immune-mediated and antibody-mediated neurological diseases such as:

  • multiple sclerosis and other demyelinating diseases
  • motor neurone disease
  • psychiatric disorders
  • movement disorders
  • dementia
  • myasthenia gravis, and more.

Our team focuses on developing new and more effective ways of diagnosing these conditions. Further, our improved understanding of the effects of autoantibodies in these disorders enables us to focus on developing new and innovative treatments.

Our collective expertise in detecting autoantibodies and other biomarkers, exploring antibody pathogenicity, neuropathology, imaging and clinical service delivery puts us at the forefront of this research. By integrating our basic laboratory research, clinically applied research and health service provision, we are able to rapidly translate our findings into real-world applications.

This research program stems from our collaboration with academics and clinicians from Westmead Hospital, the Children’s Hospital at Westmead, Westmead Institute for Medical Research, Save Sight Institute, Bosch Institute, Royal Prince Alfred Hospital, Concord Hospital, Royal North Shore Hospital and Nepean Hospital.

We are also part of the International Society of Neuroimmunology (ISNI) and our our lead researcher, A/prof Fabienne Brilot, co-chairing the third Asia-Pacific Neuroimmunology Course in June 2021. Learn more about the conference here.

Our current research streams

Our current research programs under the Sydney Neuroimmunology Framework are outlined here. Schematic by Dr Fiona Tea, HDR student, Brain Autoimmunity Group, USYD

Key publications

Epidemic viral infections predominated as causes of childhood encephalitis in Australia. The leading causes include vaccine-preventable diseases. There were significant differences in age, clinical features, and outcome among leading causes. Mortality or short-term neurological morbidity occurred in one-third of cases.

Learn more: 10.1093/cid/ciz685

Over recent years, human 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 as therapeutic and prognostic differences from multiple sclerosis are acknowledged, an in-depth characterization of human MOG Ab is required to answer key challenges in patient diagnosis, treatment, and prognosis. Herein, we investigated the epitope, binding sensitivity, and affinity of MOG Ab in a cohort of 139 and 148 MOG antibody-seropositive children and adults (n = 287 patients at baseline, 130 longitudinal samples, and 22 cerebrospinal fluid samples)

 

https://pubmed.ncbi.nlm.nih.gov/31481127/

We identify significant differences in CSF cytokine/chemokine profile between FIRES/FRD and encephalitis. The prominent elevation of CSF cytokines and chemokines in FIRES/FRD and to a lesser extent FSE highlights that the cytokine/chemokine elevation is significantly associated with the etiology of the underlying process rather than purely reactive. However, it is unclear whether the immune activation contributes to the disease process.

https://pubmed.ncbi.nlm.nih.gov/31283843/

IFIH1 gain-of-function causes a spectrum of neuroinflammatory phenotypes associated with enhanced type I interferon production and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway activation.1,2 Patients most often present in infancy, variably exhibiting spasticity, dystonia, seizures, and acquired microcephaly. We report the use of ruxolitinib, a JAK 1/2 blocker, in the treatment of early-onset, progressive neurologic disease due to an IFIH1 mutation.

https://pubmed.ncbi.nlm.nih.gov/29321238/ 

Relapsing MOG antibody-associated demyelination is strongly associated with ON across all age groups and ADEM in children. Patients are highly responsive to steroids, but vulnerable to relapse on steroid reduction and cessation.

https://pubmed.ncbi.nlm.nih.gov/29142145/

There is increasing recognition in the neurological and psychiatric literature of patients with so-called isolated psychotic presentations (ie, with no, or minimal, neurological features) who have tested positive for neuronal autoantibodies (principally N-methyl-D-aspartate receptor antibodies) and who have responded to immunotherapies. Although these individuals are sometimes described as having atypical, mild, or attenuated forms of autoimmune encephalitis, some authors feel that that these cases are sufficiently different from typical autoimmune encephalitis to establish a new category of so-called autoimmune psychosis.

https://pubmed.ncbi.nlm.nih.gov/31669058/

The availability of effective therapies for patients with relapsing-remitting multiple sclerosis (RRMS) has prompted a re-evaluation of the most appropriate way to measure treatment response, both in clinical trials and clinical practice. Traditional parameters of treatment efficacy such as annualized relapse rate, magnetic resonance imaging (MRI) activity, and disability progression have an important place, but their relative merit is uncertain, and the role of other factors such as brain atrophy is still under study. More recently, composite measures such as "no evidence of disease activity" (NEDA) have emerged as new potential treatment targets, but NEDA itself has variable definitions, is not well validated, and may be hard to implement as a treatment goal in a clinical setting. We describe the development of NEDA as an outcome measure in MS, discuss definitions including NEDA-3 and NEDA-4, and review the strengths and limitations of NEDA, indicating where further research is needed.

https://pubmed.ncbi.nlm.nih.gov/29579629/

The automated CDSS, an integrated patient smartphone application and an additional pre-screening tool were all successfully developed. Compliance with pathology monitoring was 96.7%. The automated analysis of pathology results was significantly faster than standard care neurologist review (p < 0.001). The system correctly identified and alerted abnormalities, including one case of immune thrombocytopenia (ITP) while the treating neurologist was on leave, enabling prompt treatment of serious adverse events. During the course of the study, the CDSS was deployed throughout Australia.

https://pubmed.ncbi.nlm.nih.gov/29911471/

Atypical inflammatory demyelinating syndromes are rare disorders that differ from multiple sclerosis owing to unusual clinical or MRI findings or poor response to treatments used for multiple sclerosis. These syndromes include neuromyelitis optica spectrum disorder, acute disseminated encephalomyelitis, tumefactive demyelination, Baló's concentric sclerosis, Schilder's disease, and Marburg's multiple sclerosis. The overlapping features of these syndromes with multiple sclerosis and with each other complicate diagnosis and their categorisation as distinct or related conditions.

https://pubmed.ncbi.nlm.nih.gov/27478954/