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Classifying Seronegative Myasthenia Gravis: A Comprehensive Population-Based Study

This population-based study analyzes the epidemiology of Myasthenia Gravis (MG) in Northern Ireland, focusing on the classification of cases by serological subtype, including seronegative Myasthenia Gravis (SNMG). Over a study period from January 2000 to December 2008, we identified and confirmed clinical cases, assessing variables such as age, sex, symptoms, and treatment responses. Our results demonstrate that while most MG cases present with AchR antibodies, a significant proportion remain seronegative, highlighting the importance of advanced serological techniques for accurate diagnosis and classification.

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Classifying Seronegative Myasthenia Gravis: A Comprehensive Population-Based Study

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  1. Classifying seronegative MG:A population based study A Carr1,4, MI Leite2, A Vincent2, C Cardwell3, P McCarron3, D O’Reilly3, J McConville1,4 Department of Neurology, Royal Victoria Hospital, Belfast, Northern Ireland. Neurosciences Group, John Radcliffe Hospital, University of Oxford, UK 3. Department of Medical Statistics and Epidemiology, Queens University, Belfast, Northern Ireland. 4. Department of Neurology, Ulster Hospital Dundonald, Belfast, Northern Ireland

  2. Aims • Describe the epidemiology of MG in Northern Ireland • Classify cases by serological subtype • Assess the usefulness of recently developed techniques

  3. Methods • Multiple sources of case ascertainment • Study period: 01/01/2000 – 31/12/2008 • Clinical confirmation and serological classification of individual cases • Characterisation by age, sex, symptomatology, diagnosis, treatment and co-morbidities

  4. Results • 717 possible cases • 287 excluded • 342 prevalent cases (31/12/2008) • Ascertainment= 98.2% (95%C.I.: 92.1, 99.6) • 212 incident during study period • 186 AChR MG • 26 SNMG

  5. Serological analysis • 23 SNMG • 12 AChR MG • 6 MuSK MG • 4 Healthy controls (HC)

  6. AChR+rapsyn-EGFP EGFP Serum+ anti-human IgG Serum+ anti-human IgG

  7. Cell-based immunofluorescent assay: MuSK Serum+ anti-human IgG MuSK-EGFP Merged Case Case Control

  8. Cell-based immunofluorescent assay: clustered AChR AChR+rapsyn-EGFP Serum+ anti-human IgG Merged Case Case Control

  9. Cell-based immunofluorescent assay

  10. Characteristics of serological subgroups No difference. ANOVA; p: 0.065 No difference. 2; p>0.5 No difference. ANOVA; p: 0.898 No difference. ANOVA; p: 0.393

  11. Incidence rate (cases per million person-years)

  12. Conclusions • Cell based assays improve serological classification of autoimmune MG • A proportion of cases remain seronegative

  13. Acknowledgements Prof Angela Vincent, Neurosciences group, Oxford University Dr Isabel Leite, Neurosciences group, Oxford University

  14. Neuromuscular junction • AChR ab in 80% • MuSK ab in 10% • SNMG 10% Motor neurone Muscle end plate Acetylcholine receptor MuSK Dok-7 Rapsyn Acetylcholine vesicle Pre-synaptic Ca2+ channel

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