1. Classifying seronegative MG: A population based study A Carr 1,4, MI Leite 2, A Vincent 2, C Cardwell 3, P McCarron 3, D O’Reilly 3, J McConville 1,4 1.Department of Neurology, Royal Victoria Hospital, Belfast, Northern Ireland. 2.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 1.Describe the epidemiology of MG in Northern Ireland 2.Classify cases by serological subtype 3.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. EGFP AChR+ rapsyn-EGFP Serum+ anti-human IgG Serum+ anti-human IgG

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

8. AChR+ rapsyn-EGFP Serum+ anti-human IgG Merged Cell-based immunofluorescent assay: clustered AChR 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: 0.898No difference. ANOVA; p: 0.393

11. Incidence rate (cases per million person-years) CIR (x10 -6) Number95% C.I. All MG13.921212.215.8 AChR MG12.318610.714.1 (Low affinity AChR ab0.580.21.0) MuSK MG0.130.030.5 SNMG0.8120.51.4 PNP MG0.90.5 1.6

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 Muscle end plate Motor neurone AChR ab in 80% MuSK ab in 10% SNMG 10% Acetylcholine receptor MuSK Dok-7 Rapsyn Acetylcholine vesicle Pre-synaptic Ca 2+ channel