Prof Angela Vincent FRS FMedSci FRCP FRCPath

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Fig 1. Binding of patient’s serum antibodies (red stain) to acetylcholine receptors clustered on the surface of a transfected cell line (from Leite et al 2008).

Fig 1. Binding of patient’s serum antibodies (red stain) to acetylcholine receptors clustered on ...

Fig 2.  MRI showing high signal (white) in both hippocampi
of a patient with recent onset of memory loss and seizures
and high levels of antibodies to voltage-gated potassium channels.

Fig 2. MRI showing high signal (white) in both hippocampi of a patient with recent onset of ...

Clinical and Experimental Neuroimmunology studies diseases caused by autoantibodies to ion channels and other targets in the peripheral and central nervous system. We use a variety of approaches to define new antibody-mediated diseases, particularly 125I-neurotoxins to label relevant ion channels, cell lines expressing recombinant antigens, and immunostaining of brain tissue with patients’ sera.

 

Antibodies to acetylcholine receptors (AChR) are found in >85% of patients with myasthenia gravis (MG), which usually arises in adult life. The role of the thymus and how genetic polymorphisms influence disease are the focus of current study.  A particular interest is the 15% of patients with MG who do not have AChR antibodies. Many have antibodies to the muscle specific kinase, MuSK (Hoch et al 2001); some of these are children who develop severe muscle atrophy.  Current work aims to establish how these antibodies cause the disease, and how the muscle atrophy arises.  The remaining patients appear to have low affinity AChR antibodies that are only detectable using new cell-based approaches: these include binding to the AChR clustered on the surface of transfected cells (Fig 1).

Antibodies can cause central nervous system (CNS) disorders. Antibodies to voltage-gated potassium channels are found in neuromyotonia, a condition of acquired motor hyper-excitability; but in some cases the patients also have seizures, memory loss, sleep disorders, and “psychiatric” symptoms.  These patients often have inflammation and swelling of the hippocampus – the part of the brain that is most involved in laying down memories (Fig 2).  The condition improves remarkably following immuno-suppression.

We have begun to detect autoantibodies to a variety of ion channels and receptors in both the peripheral and central nervous systems using novel approaches.  These antibodies include those to NMDA receptors, glycine receptors and aquaporin-4.  Identification of such an antibody, in a previously well patient, often means that they can be treated with immunotherapies with good prospects for recovery.

The relationship between serum antibodies and CNS diseases is being studied by Buckley (MRC Clinician Scientist) who also has an experimental and clinical interest in narcolepsy. 

Agashe (Departmental Fellow) is developing an independent group studying the link between unfolded protein responses and neurodegeneration in a variety of in vitro and in vivo models.

 

Biography

Angela Vincent (Hon PhD Bergen) FRCPath FRCP FMedSci is Emeritus Professor of Neuroimmunology in the University  of Oxford, and an Emeritus Fellow of Somerville College.  She still holds an Honorary Consultant position in Immunology and runs the Clinical Neuroimmunology service which is an international referral centre for the measurement of antibodies in neurological diseases.  She and her colleagues collaborate with neurologists worldwide. She was formerly Head of Department of Clinical Neurology (2005-2008), and is a Past President of the International Society of Neuroimmunology, and an Associate Editor of Brain.  She was a co-applicant and group leader of OXION, the Wellcome Trust-funded Integrative Physiology Initiative "Ion channels and Diseases of Electrically Excitable Cells". She is a member of Faculty of 1000 (Neuroscience, Neurobiology of Disease and Regeneration). Clinical neuroimmunology is one of the subthemes of the recently awarded NIHR-funded Oxford University/Oxford Radcliffe Hospital Trust Biomedical Research Centre. The work of her group is supported by the MRC, the Wellcome Trust, the Muscular Dystrophy Campaign, the DoH, the Patrick Berthoud Trust, the EU, the PNSneuronet for work on paraneoplastic diseases, and the Euromyasthenia network.

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