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VINCENT Angela

Tel.: +44 1865 222321

Fax: +44 1865 222402

e-mail: angela.vincent@imm.ox.ac.uk

 

Address

Neurosciences GroupBiomedical Research Insitute

Department of Clinical Neurology

Institute of Molecular Medicine

John Radcliffe Hospital

Oxford OX3 9DS - UK

Research themes

Role of antibodies in neurological diseases at the neuromuscular junction and central nervous system. Antibodies directed towards ion channels in the central nervous system in patients with memory loss, epilepsy and other problems, and new animal models for examining their mechanisms. Identification of antigenic targets in seronegative MG, and investigation of the role of antibodies to muscle specific kinase in causing muscle atrophy. Maternal antibodies in neurodevelopmental disorders such as autism. Measurement of antibodies to neuronal antigens for the diagnosis of immune-mediated diseases in clinical neurology.

Key words

Antibodies, ion channels, autoimmune diseases, paraneoplastic diseases, maternal-to-fetal transfer

Methods

Cellular immunology (T cell isolation and cloning, proliferation and cytotoxic assays, FACS analysis), protein analyses (2D-PAGE, IEF, Western blotting), molecular biology (DNA cloning, sequencing, PCR, immunoscope), cytokine quantification (ELISA, quantitative PCR), immunohistochemistry, immunogenetics (SNP's and microsatellites), apoptosis detection, cDNA phage display, serological antigen selection (SAS)

Composition of the research group (Includes *independent scientists/clinicians)

Linda CLOVER

BSc Research Assistant

Maria Farrugia

MD Fellow

Nemesha Desai

MD Fellow

Warren TAYLOR

MSc Technician

Mary McMenamin

Postdoctoral Fellow

*Bethan LANG

PhD Biochemistry

*David BEESON

PhD Molecular Biology

*Nicholas WILLCOX

MD PhD Cellular Immunology

*Angela VINCENT

MD FRCPath Humoral Immunology

Recent publications

  1. RIEMERSMA S, VINCENT A, BEESON D, NEWLAND C, BRUETON L, HUSON S, NEWSOM-DAVIS J. 1996. Association of arthrogryposis multiplex congenita with maternal antibodies inhibiting fetal acetylcholine receptor function. J Clin Invest, 98:2358-2363.

  2. HART I, WATERS C, VINCENT A, NEWLAND C, BEESON D, PONGS O, MORRIS C, NEWSOM-DAVIS J. 1997. Autoantibodies detected to expressed K+ channels are implicated in neuromyotonia. Ann Neurol 41, 238-246.

  3. FARRAR J, PORTOLANO S, WILLCOX N, VINCENT A, JACOBSON L, NEWSOM-DAVIS J, RAPOPORT B, MCLACHLAN SM. 1997. Diverse Fab specific for acetylcholine receptor epitopes from a myasthenia gravis thymus combinatorial library. Int Immunol 9: 1311-1318.

  4. CURNOW J, WILLCOX N, VINCENT A. 1998 Induction of primary immune responses by allogeneic human myoblasts: dissection of the cell types required for proliferation, IFNg secretion and cytotoxicity. J Neuroimm, 86 53-62.

  5. PLOMP JL, MOLENAAR PC, O'HANLON GM, JACOBS BC, VEITCHJ, DAHA MR, VAN DOORN PA, CAN DER MECHE FGA, VINCENT A, MORGAN BP, WILLISON HJ. MILLER FISHER anti-GQ1b antibodies: a-latrotoxin like effects on motor end plates. Ann Neurol 1999; 45: 189-199.

  6. JACOBSON L, POLIZZI A, MORRISS-KAY GM, VINCENT A 1999 An animal model of antibody-mediated neurodevelopmental disease: arythrogryposis multiplex congenita caused by antibodies to fetal acetylcholine receptor. J Clin Invest 103; 1031-1038.

  7. JACOBSON L, BEESON D, TZARTOS S, VINCENT A. 1999 Monoclonal antibodies raised against human acetylcholine receptor bind to all five subunits of the fetal isoform. J Neuroimmunol. 98: 112-120.

  8. BLAES F, BEESON D, PLESTED P, LANG B, VINCENT A. IgG from seronegative myastyhenia gravis patients binds to TE671 cells but not to human AChR expressed in HEK cells. Ann Neurol in press 2000.

  9. BRUETON LA, HUSON SM, COX PM, SHIRLEY I, THOMPSON EM, BARNES PRJ, PRICE J, DEWSON-DAVIS J, VINCENT A. Asymptomatic maternal myasthenia as a cause of Pens-Shokeir phenotype. Am J Med Genetics, in press 2000.

  10. CURNOW J, CORLETT L, WILLCOX N, VINCENT A. 2001 Presentation by myoblasts of an epitope from endogenous acetylchoie receptor indicates a potential role in the spreading of the immune response. J Neuroimmunol 115, 127-134.

  11. SUTTON IJ, FURSDON DAVIS CJ, ESIRI MM, HUGHES S, AMYES ER, VINCENT A. 2001 Anti-Yo antibodies and cerebellar degeneration in a man with adenocarcinoma of the esophagus. Ann Neurol 49: 253-257.

  12. BUCKLEY C, DUECK D, NEWSOM-DAVIS J, VINCENT A, WILLCOX N. 2001. Mature, long-lived CD4 and CD8 T cells are generated by thymoma in myathenia gravis. Ann Neurol 50: 64-73 .

  13. BUCKLEY C, OGER J, CLOVER L, TUZUN E, CARPENTER K, JACKSON M, VINCENT A. 2001. Potassium channel antibodies in two patients with reversible limbic encephalitis. Ann Neurol 50: 74-79

  14. BUCKLEY C, WILLCOX N, NEWSOM-DAVIS J, VINCENT A. 2001. Do titin and cytokine antibodies in MG patients predict thymoma or thymoma recurrence? Neurology. 2001 Nov 13;57(9):1579-82

  15. LIGUORI R, VINCENT A, CLOVER L, AVONI P, PLAZZI G, CORTELLI P, BARUZZI A, CAREY T, GAMBETTI P, LUGARESI E, MONTAGNA P. Morvan's syndrome: peripheral and central nervous system and cardiac involvement with antibodies to voltage-gated potassium channels. Brain 2001 124: 2417-2426.

  16. KNOWLES CH, LANG B, CLOVER L, SCOTT SM, GOTTI C, VINCENT A, MARTIN JE. A role for autoantibodies in some cases of acquired non-paraneoplastic gut dysmotility. Scand J Gastroenterol. 2002;37:166-70.

  17. GATTENLOHNER S, SCHNEIDER C, THAMER C, KLEIN R, ROGGENDORF W, GOHLKE F, NIETHAMMER C, CZUB S, VINCENT A, MULLER-HERMELINK H-K, MARX A. Expression of fetal type acetylcholine receptor is restricted to type I muscle fibres in human neuromuscular disorders Brain. 2002;125:1309-19.

  18. HART IK, MADDISON P, NEWSOM-DAVIS J, VINCENT A, MILLS K. Phenotypic variants of autoimmune peripheral nerve hyperexcitability Brain, Vol. 125, No. 8, 1887-1895, 200219.

  19. GRAUS F, LANG B, POZO-ROSICH P, SAIZ A, CASAMITJANA R, VINCENT A. P/Q type calcium channel antibodies in paraneoplastic cerebellar degeneration with lung cancer. Neurology 2002; 59; 764-766.

  20. VINCENT A, DEACON R, DALTON P, SALMOND C, BLAMIRE AM, PENDLEBURY S, JOHANSEN-BERG H, RAJOGOPALAN B , STYLES P, STEIN J. 2002. Maternal antibody-mediated dyslexia? Evidence for a pathogenic serum factor in a mother of two dyslexic children shown by transfer to mice using behavioural studies and magnetic resonance spectroscopy J NeuroImmunol 130: 243-247.

  21. VAN PARIJS V, VINCENT A, VAN DEN BERGH PYK. Neuromyotonia and myasthenia gravis without thymoma: a case report. J Neurol Neurosurg Psychiatr 2002; 73: 344-345.

  22. MATTHEWS I, SIMS G, LEDWIDGE S, STOTT D, WILLCOX N, VINCENT A Antibodies to acetylcholine receptor in parous women with myasthenia: evidence for immunization by fetal antigen. Lab Invest. 2002;82:1407-17

  23. PLESTED, CP, T. TANG, I. SPREADBURY, E.T. LITTLETON, U. KISHORE, AND A. VINCENT. AChR phosphorylation and indirect inhibition of AChR function in seronegative MG Neurology 2002; 59: 1682-8

  24. EALING J, WEBSTER R, BROWNLOWS, ABDELGANY A, OOSTERHUIS H, MUNTONI F, VAUX DJ, VINCENT A, BEESON D. Mutations in congenital myasthenic syndromes reveal an varepsilon subunit C-terminal cysteine, C470, crucial for maturation and surface expression of adult AChR. Hum Mol Genet. 2002 ;11:3087-3096.

  25. DALTON P, DEACON R, BLAMIRE AM, PIKE M, MCKINLAY I, STEIN J, STYLES P, VINCENT A. Experimental evidence for a fetopathogenic antibody in the mother of children with autism and a severe speech disorder. Ann Neurol 2003 : 53:533-7.

  26. SANDERS DB, EL-SALEM K, MASSEY JM, MCCONVILLE J, VINCENT A. Clinical aspects of MuSK antibody positive seronegative MG. Neurology. 2003 Jun 24;60(12):1978-80.

  27. SCHOTT JM, HARKNESS K, BARNES J, ROCCHETTA I, VINCENT A, ROSSOR MN. Amnesia, cerebral atrophy, and autoimmunity. Lancet 2003; 361:1266.

  28. SHIONO H, WONG YL, MATTHEWS I, LIU JL, ZHANG W, SIMS G, MEAGER A, BEESON D, VINCENT A, WILLCOX N. Spontaneous production of anti-IFN-alpha and anti-IL-12 autoantibodies by thymoma cells from myasthenia gravis patients suggests autoimmunization in the tumor. Int Immunol. 2003 Aug;15(8):903-913

  29. VINCENT A, CLOVER L, GRIMLEY-EVANS J, ROTHWELL P. Incidence of myasthenia in the elderly. J Neurol Neurosurg Psychiatry. 2003 Aug;74(8):1105-8.

  30. LAWRENCE N, OGER J, AZIZT, PALACE J, VINCENT A. A sensitive radioimmunoprecipitation assay for assessing the clinical relevance of antibodies to INF . J Neurol Neurosurg Psychiatry. 2003 Sep;74(9):1236-9.

  31. POZO-ROSICH P, CLOVER L, SAIZ A, VINCENT A, GRAUS F. Voltage-gated potassium channel antibodies in idiopathic and paraneoplastic limbic encephalitis. Ann Neurol. 2003 Oct;54(4):530-3.

  32. BURKE G, COSSINS J, MAXWELL S, OWENS G, VINCENT A, ROBB S, NICOLLE M, HILTON-JONES D, NEWSOM-DAVIS J, PALACE J, BEESON D. Rapsyn mutations in hereditary myasthenia: Distinct early- and late-onset phenotypes. Neurology. 2003 Sep 23;61(6):826-828.

  33. LILY O, PALACE J, VINCENT A Serum autoantibodies to cell surface determinants in multiple sclerosis: systematic analysis of antibodies binding to humanc ells by flow cytometry. Brain 2004;127):269-79.

  34. VINCENT A, BUCKLEY C, SCHOTT JM, BAKER I, DEWAR B-K, DETERT N, CLOVER L, PARKINSON A, BIEN CG, OMER S, LANG B, ROSSOR M, PALACE J. Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis Brain in press.

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