Neuroimmunology Group, Institute for Neuroscience and Muscle Research

Lab head: Dr Fabienne Brilot-Turville
Location: Kids Research Institute, Children's Hospital at Westmead

Lab members: K North (depthead), K North (head), S Cooper (inmr-dmrt), N Clarke (inmr-mmdt), B Barton (inmr-nft), R Webster (inmr-nft), J Burns (inmr-crt), E Oates (inmr-crt), R Dale (inmr-nit), F Brilot-Turville (inmr-nit), S Pillai (inmr-nit), B Owler (inmr-nst)
Funding: NHRMC, the Star Scientific Foundation, Multiple Sclerosis Research Australia
Research approach equipment: Our focus is to identify new targets of antibodies and to study the role of these antibodies in the pathogenesis of brain immune-mediated diseases in children. Our group is part of the Institute for Neuroscience and Muscle Research at the Kids Research Institute (the Children's Hospital at Westmead). The Kids Research Institute is a global leading translational research center for children associated with the University of Sydney. It is located in a brand new building besides the Children's Hospital at Westmead. Also present on the Westmead campus are the Westmead Millenium Institute and the Children Medical Research research Institute. The three institutes share state-of-the-art facilities including flow cytometry, imaging, genomics, and proteomics cores.
Publications:

Dale RC, Tantsis E, Merheb V, Brilot F. Cerebrospinal fluid B-cell expansion in longitudinally extensive transverse myelitis associated with neuromyelitis optica immunoglobulin G. Dev Med Child Neurol 2011; 53(9): 856-60 (I.F.: 3.09)

Pröbstel AK, Dornmair K, Bittner R, Sperl P, Jenne D, Magalhaes S, Villalobos A, Breithaupt C, Weissert R, Jacob U, Krumbholz M, Kümpfel T, Blaschek A, Stark W, Gärtner J, Pohl D, Rostasy K, Weber F, Forne I, Khademi M, Olsson T, Brilot F, Tantsis E, Dale RC, Wekerle H, Hohlfeld R, Banwell B, Bar-Or A, Meinl E, and Derfuß T. Antibodies to MOG are transient in childhood acute disseminated encephalomyelitis. Neurology 2011; 77(6): 580-8 (I.F.: 8.172)

Dale RC, Yin K, Ding, Merheb V, Varadkhar S, McKay D, Singh-Grewal D & Brilot F.  Antibody binding to neuronal surface in movement disorders associated with lupus and anti-phospholipid antibodies. Dev Med Child Neurol 2011; 53(6): 522-8 (I.F.: 3.09)

Suleiman J, Brenner T, Gill D, Brilot F, Jayne A, Vincent A, Kang B & Dale RC. KGKC antibodies in paediatric encephalitis presenting with status epilepticus. Neurology 2011; 76(14): 1252-5 (I.F.: 8.172)

Brilot F, Merheb V, Ding A, Murphy T & Dale RC. Antibody binding to neuronal surface in Sydenham chorea, but not in PANDAS or Tourette syndrome. Neurology 2011; 76(17): 1508-13(I.F.: 8.172)

Selter RC, Brilot F, Grummel V, Kraus V, Cepok S, Dale RC & Hemmer B.Antibody responses to EBV and native MOG in pediatric inflammatory demyelinating CNS diseases. Neurology 2010; 74(21): 1711-15 (I.F.: 8.172)

Brilot F, Dale RC, Selter RC, Grummel V, Reddy Kalluri S, Aslam M, Busch V, Zhou D, Cepok S & Hemmer B. Antibodies to native MOG in children with inflammatory demyelinating CNS disease. Ann Neurol 2009; 66(6): 833-42  (I.F.: 9.9)

Dale RC, Irani SR, Brilot F, Pillai S, Webster R, Gill D, Lang B & Vincent A. Pediatric dyskinetic encephalitis lethargica is an NMDA receptor encephalitis. Ann Neurol 2009; 66(5): 704-09 (I.F.: 9.9)

Dale RC, Brilot F, Fagan E & Earl J. CSF neopterin in paediatric neurology: a marker of active CNS inflammation. Dev Med Child Neurol 2009; 51(4): 317-23(I.F.: 3.09)

Antibody to brain antigens in encephalitis in children: how to prevent disabilities

Primary supervisor: Fabienne Brilot-Turville

Brain immune-mediated diseases, such as first episode of demyelination, encephalitis, Sydenham’s Chorea, and neuropsychiatric Lupus, occur frequently and affect the brain of children. Their symptoms are depression, psychosis, sleep disorders, seizures, and a full range of movement disorders. Finding a treatment is challenging, and therefore they often lead to neurological disability. A humoral (B cell and antibody) autoimmune response has been identified in subgroups of children. The targets of the attack are important brain proteins against which antibodies are raised, such as neurotransmitter receptors, or voltage-gated ion channels. This discovery has raised new hope for the treatment of these children as humoral immunity-targeted therapies, such as plasma exchange and B cell-depleting anti-CD20 antibody therapy (Rituximab) have shown promising results in adults.

Our research program is articulated around two main arms: the first one is to identify brain antigens against which antibodies are raised in these diseases in order to provide diagnostic and treatment option. The second one is to determine whether these autoantibodies are pathogenic and participate in brain damage.

Our research will greatly improve the knowledge of B cell-dependent brain immune-mediated diseases with direct translational effects into the care of these patients.

Techniques: Cellular models have been engineered to express important brain antigens. Antigen expression will be determined using western blotting and immunocytochemistry. The binding of autoantibodies from patient and control sera will be determined using flow cytometry and confocal fluorescence microscopy. Their potential action on neuron physiology will be examined using primary cultures of murine neurons and live cell imaging.

Interested students are strongly advised to contact the project supervisor to discuss potential honours and Ph.D. projects (fabiennb@chw.edu.au).

Discipline: Infectious diseases and Immunology
Co-supervisors: Russell Dale
Keywords: Antibody, Neuroimmunology, Brain
Contact: Email Fabienne Brilot-Turville