Myasthenia gravis among Hungarians - PowerPoint PPT Presentation

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Myasthenia gravis among Hungarians

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  1. Myasthenia gravis among Hungarians Zsolt Illes Department of Neurology University of Pecs Pécs

  2. database and tissue bank at Pecs • University of Pecs, Department of Neurology, Pecs • Jahn Ferenc Teaching Hospital, Department of Neurology, Budapest Pécs Budapest • 225 samples • sera • DNA • clinical data • 225 analyzed for anti-AchR antibodies • 149 analyzed for anti-Titin antibodies • 36 analyzed for anti-MuSK antibodies

  3. sex ratio 100 n=225 80 60 n 147 Percentage 40 n 78 20 0 F M

  4. age at the time of diagnosis n=175 mean age: 44.6 years 45 40 40 35 30 28 25 25 24 number of patients 20 21 19 15 16 10 5 2 0 0 1-10 11-20 21-30 31-40 41-50 51-60 61-70 71-80 81- age (years)

  5. age at the time of diagnosis: females n=109 mean age: 37.7 years 40 35 36 30 25 number of patients 20 18 15 16 13 10 11 8 5 1 6 0 0 1-10 11-20 21-30 31-40 41-50 51-60 61-70 71-80 81- 64% age (years)

  6. age at the time of diagnosis: males n=66 mean age: 56.1 years 20 19 15 17 number of patients 10 11 8 5 1 1 0 4 5 0 1-10 11-20 21-30 31-40 41-50 51-60 61-70 71-80 81- age (years) 68%

  7. anti-AchR antibody total female male n=175 n=109 n=66 100 80 80.6 77.1 86.4 60 percentage 40 20 22.9 19.4 13.6 141 34 84 25 57 9 number of patients number of patients number of patients anti-AchR positive anti-AchR negative

  8. anti-Titin antibody total female male n=149 n=94 n=55 100 80 60 percentage 61.8 76.5 85.1 40 38.2 20 23.5 14.9 35 114 14 80 21 34 number of patients number of patients number of patients anti-titin positive anti-titin negative

  9. combination of antibodies anti-AchR 175 patients anti-AchR+: 141 80.6% anti-AchR-: 34 19.4% + - 149 patients anti-AchR+: 117 79% anti-AchR-: 32 21% 100 100 80 80 - + 60 60 40 40 9% 20 20 27% 0% 31% 0 0 anti-Titin 32/117 anti-Titin 3/32 anti-MuSK 0/23 anti-MuSK 4/13

  10. combination of antibodies anti-Titin 149 patients anti-Titin+: 114 23.5% anti-Titin-: 35 76.5% - + + - 100 100 91% 74% 80 80 60 60 14% 0% 40 40 anti-AchR 32/35 anti-AchR 85/114 anti-MuSK 0/7 anti-MuSK 4/29 20 20 0 0

  11. genetic heterogeneity: PTPN22 n Genotype Allele frequency P OR TT CT CC T(%) C (%) [95% CI] Control 379 5 (1) 75 (20) 299 (79) 85 (11) 673 (89) No thymoma 208 3 (1) 56 (27) 149 (72) 62 (15) 354 (85) 0.07 1.39 [0.98-1.97] anti-Titin + 50 1(2) 19 (38) 30 (60) 21 (21) 79 (79) 0.005 2.10 [1.23-3.58] anti-Titin - 152 2(1) 35 (23) 115 (76) 39 (13) 265 (87) 0.4 1.17 [0.78-1.75] 1.46 [1.00-2.12] anti-AchR + 164 2(1) 47 (29) 115 (70) 51 (16) 277 (84) <0.05 anti-AchR - 42 1(2) 8 (19) 33 (79) 10 (12) 74 (88) 0.84 1.07 [0.53-2.15] Thymoma 33 0(0) 7 (21) 26 (79) 7 (11) 59 (89) 0.88 0.94 [0.42-2.12] Greve et al, Hum Immunol, 2009

  12. genetic heterogeneity wt minor ICOS 20 16.8 16 12.2 11.6 minor allele frequency 12 8 4.3 4 1.7 0 Titin+ total control AchR– DRB1*1501 MG MS

  13. ocular vs generalized: 5 yearsretrospectively n=71 ocular onset limb percentage of patients 44% 56% female (EOMG) 59% 76% male (LOMG) 41% 24% • anti-AchR: • AchR + • AchR - 77% 23% 79% 21% time to diagnosis 4.7 months 12.4 months MGFA at diagnosis I: all 100% II:76% III:17% IV:7% generalization over 5 years: 83 %

  14. thymectomy sex all female age at diagnosis 24 years (11-56) • serology • anti-AchR+ • anti-AchR- • anti-MuSK • anti-Titin 77 % 23% 0.07 % 0 % time to operation 23 months (2-132) • pathology • thymoma • hyperplasia 31 % 69 % • complete remission • thymoma • hyperplasia 75 % 55 % • therapy • thymoma • hyperplasia pyr (30%) / AZA (30%) / AZA+pyr (30%) nothing (20%) /pyr (40%) /AZA (40%)

  15. associated (autoimmune) diseases n=71 • Hashimoto thyreoditis 5.8 % • hypothyreosis 0.2 % • hyperthyreosis 0.2 % • antiphospholypid syndrome 0.2 % • MGUS 0.2 % • all anti-AchR positive • Hodgkin lymphoma 1 patient • post-irradiation sarcoma? anti-MuSK positive • anti-TPO 1 % • anti-TG 0.2 % all anti-AchR positive

  16. anti-MuSK n=4 sex all female • age at diagnosis • EOM • LOM 3 75 % 1 25 % • serology • anti-AchR • anti-Titin • anti-MuSK none 0 % none 0 % all 4 100 % bulbar symptoms all crisis • all • 11 crisis and 13 PE during 7 years • 3 crisis and 4 PE during 4 years paraneoplasia in one?

  17. acknowledgement University of Pecs, Hungary Csilla Rozsa, Samuel Komoly, Renata Vegh, Blanka Kellermayer, Miklos Banati University of Tübingen Bernhard Greve, Arthur Melms Oxford University Angela Vincent