Contact Details

http://www.neuroscience.ox.ac.uk/directory/angela-vincent

References

Jacobson L, Polizzi A, Morriss-Kay G, Vincent A. Plasma from human mothers of fetuses with severe arthrogryposis multiplex congenita causes deformities in mice. J Clin Invest 1999;103(7):1031-8.

Hoch W, McConville J, Helms S, Newsom-Davis J, Melms A, Vincent A. Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat Med 2001;7(3):365-8.

Vincent A, Buckley C, Schott JM, Baker I, Dewar BK, Detert N, et al. Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis. Brain 2004;127(Pt 3):701-12.

Farrugia ME, Robson MD, Clover L, Anslow P, Newsom-Davis J, Kennett R, et al. MRI and clinical studies of facial and bulbar muscle involvement in MuSK antibody-associated myasthenia gravis. Brain 2006;129(Pt 6):1481-92.

Vincent A, Lang B, Kleopa KA. Autoimmune channelopathies and related neurological disorders. Neuron 2006;52(1):123-38.

Bien CG, Urbach H, Schramm J, Soeder BM, Becker AJ, Voltz R, et al. Limbic encephalitis as a precipitating event in adult-onset temporal lobe epilepsy. Neurology 2007;69(12):1236-44.

Leite MI, Jacob S, Viegas S, Cossins J, Clover L, Morgan BP, et al. IgG1 antibodies to acetylcholine receptors in 'seronegative' myasthenia gravis. Brain 2008;131(Pt 7):1940-52.

Waters P, Jarius S, Littleton E, Leite MI, Jacob S, Gray B, et al. Aquaporin-4 antibodies in neuromyelitis optica and longitudinally extensive transverse myelitis. Arch Neurol 2008;65(7):913-9.

Professor Angela Vincent

Emeritus Professor of Neuroimmunology, University of Oxford

Professor of Neuroimmunology, UCL, Institute of Neurology

Professor Angela Vincent

The work of my group in the past has encompassed both genetic and autoimmune diseases of ion channels and receptors at the neuromuscular junction. Recent activities have shown the involvement of antibodies in central nervous system (CNS) disease. My current work, therefore, aims to broaden the search for new peripheral and central disease-related antibodies by testing candidate antigens and using a cell membrane antigen identification proteomic protocol that we have developed. In the future it will also be important to develop further molecular and cellular approaches to provide more sensitive and convenient diagnostic assays, and to establish appropriate models for the investigation of these pontentially treatable disorders.

Myasthenia gravis:

Much of our work has aimed to dissect the different forms which we first distinguished on the basis of HLA types and thymic pathologies, and subsequently by demonstrating different antibodies in patients without detectable acetylcholine receptor (AChR) antibodies. We found that antibodies in these patients can affect AChR function in a reversible manner and recently demonstrated that they bind to the AChRs when expressed at high density on cell lines. Other patients have antibodies, instead, to the muscle specific kinase (MuSK) which is a receptor tyrosine kinase essential for development of the neuromuscular junction. Interestingly, the MuSK antibodies vary in frequency worldwide, the patients have few thymic abnormalities unlike the AChR antibody positive patients, but they often develop severe facial and bulbar muscle weakness. Recent evidence indicates that the MuSK antibodies up-regulate muscle atrophy-related gene expression, but it is not clear yet how this happens. Animal models are on-going to dissect more closely the pathogenic mechanisms in these forms of myasthenia.

Maternal antibodies and developmental disorders:

Some rare cases of recurrent arthrogryposis multiplex congenita (multiple joint contractures, and other deformities) are associated with AChR antibodies that directly inhibit the function of the fetal AChR isoform, whilst leaving the adult isoform unaffected. We developed a novel model for this disorder by injecting pregnant mouse dams with the maternal serum or plasma; the human IgG was transferred efficiently to the mouse fetuses and caused paralysis and joint deformities in the offspring. We are developing this theme further to look for antibodies in mothers of children with other neurodevelopmental disorders such as some forms of autism.

Ion channel and receptor antibodies in peripheral and central disorders:

There is increasing evidence for antibodies that bind potassium channels (extracted from brain tissue) in acquired hyperexcitability syndromes such as neuromyotonia and cramp fasciculation syndrome. The patients improve with immunosuppression although anti-epileptic drugs are often effective. There can also be autonomic and central nervous system involvement in the rare Morvan’s syndrome, and increasingly we are identifying patients with a pure limbic encephalitis, usually presenting with memory loss and seizures, but often developing neuropsychiatric features and sleep disorders. Both these conditions also improve substantially with immunosuppressive treatments, although the patients may be left with residual dysfunction. We are trying to define the targets of these antibodies more precisely, and to demonstrate their pathogenicity in model systems. The field of CNS antibodies is beginning to develop rapidly with antibodies to NMDA receptors, glycine receptors and aquaporin 4 identified in patients with different immunotherapy-responsive syndromes.