Neuroimmunology

Brain immune-mediated disorders present in previously normal children and result in rapid alteration in neurological function.  Children can become acutely blind, have disturbed movement, altered behaviour and psychiatry, loss of memory, or new onset severe seizures.  The Neuroimmunology group’s aim is to identify novel or established autoantibodies and their role in children presenting with these disorders.  These antibodies can be biomarkers and they can be used in early diagnosis and potentially early intervention with immune therapies.  These autoantibodies can also be pathogenic: i.e. they can directly cause the diseases.  One of the group’s priorities is to allow early treatment to improve the outcome of these children with altered brain function.

The Neuroimmunology group has three main research avenues:

1)      Autoantibodies against Myelin Oligodendrocyte Glycoprotein in childhood brain demyelination and multiple sclerosis.

Multiple sclerosis is the commonest cause of neurological disability in young adults in the world.  Multiple sclerosis is a relapsing disorder which causes progressive impairment of neurological function.  Up to 10% of patients will present in childhood with their first attack. In 2009, we published a paper in “Annals in Neurology” one of the most prestigious journals in Neurology.  We found autoantibodies against Myelin Oligodendrocyte Glycoprotein (MOG) in children with a first episode of brain demyelination.  MOG is a protein in the white matter of the brain which is one of the primary targets in multiple sclerosis.  Our findings showed that these antibodies were highly present in children with acute demyelination, and at higher levels than seen in adults with multiple sclerosis.  Therefore children provide novel opportunity to understand the earliest aspects of brain demyelination and multiple sclerosis. Our work will be to try to establish whether these antibodies are causing disease.  We will also be determining whether there is any association with genetic risk factors, and whether the antibodies are predictive of multiple sclerosis in the future.

2)       Autoantibodies against NMDA Receptor in childhood autoimmune encephalitis.
Children with encephalitis present dramatic agitation, psychosis, movement disorder, altered thinking, and sometimes epilepsy.  These patients are often sick, and require three-month or longer admissions.  In 2007, autoantibodies that bind to the important glutamate receptor (NMDA receptor) were found in a subgroup of adults and children with encephalitis.  These patients have autoantibodies in their blood and spinal fluid against the NMDA receptor.  Early diagnosis followed by suited immune-based treatment are essential for improvement and total recovery.  Our group’s priority is to identify the frequency of this encephalitis in childhood, the clinical spectrum, and also examine pathogenic affects of these antibodies on neuronal function.

3)       Other autoantibodies in neurological syndromes.
Our group is directly involved in a search for novel autoantibodies and is also collaborating with international groups in other neurological syndromes:
  • We are seeking possible novel autoantibodies in other autoimmune movement disorders including Sydenham chorea, PANDAS, and autoimmune Parkinsonism.
  • We are investigating autoimmune mechanisms in paediatric epilepsy including the role of Voltage-gated potassium channel antibodies in paediatric epilepsy.
  • We are investigating the role of novel autoantibodies in cerebellar disorders, such as cerebellitis and post-infectious ataxia.
  • We are interested in the role of neuromyelitis optica IgG and longitudinally extensive transverse myelitis in children with first episode of demyelination.
  • We are also interested in the role of autoantibodies in movement disorders associated with systemic autoimmune disorders, such as Systemic lupus erythematosus.

Funding

The group is very grateful to receive funding from the University of Sydney postdoctoral fellowship scheme (both Dr Russell Dale and Dr Fabienne Brilot), the Early Career Researcher University of Sydney funding scheme, the Pfizer neuroscience awards, Tourette Syndrome Association, Brain Foundation Australia and the Trish Foundation Multiple Sclerosis Foundation, and Multiple Sclerosis Research Australia.  In 2010, Drs Fabienne Brilot and Russell Dale were awarded a NHRMC new investigator project grant for their work on NMDAR encephalittis.  The neuroimmunology group is particularly grateful for the recent funding from the Star Scientific Foundation which is supporting our work into brain demyelination and multiple sclerosis in children.