1. Department of Neurology
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 F M

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

6. age at the time of diagnosis: males1 4 5 11 17 19 8 10 15 20
1-10
11-20
21-30
31-40
41-50
51-60
61-70
71-80
81-
n=66
mean age: 56.1 years
number of patients
age (years)
68%

7. anti-AchR antibody anti-AchR positive anti-AchR negative n=175 total20 40 60 80
100
141 34
n=175
number of patients
percentage
total
80.6
19.4 84 25
n=109
female
number of patients
77.1
22.9
13.6 57 9
n=66
male
86.4

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

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

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

11. genetic heterogeneity: PTPN22
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 [ ]
anti-Titin + 50
1(2)
19 (38)
30 (60)
21 (21)
79 (79)
0.005
2.10 [ ]
anti-Titin -
152
2(1)
35 (23)
115 (76)
39 (13)
265 (87)
0.4
1.17 [ ]
1.46 [ ]
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 [ ]
Thymoma 33
0(0)
7 (21)
26 (79)
7 (11)
59 (89)
0.88
0.94 [ ]
Greve et al, Hum Immunol, 2009

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

13. ocular vs generalized: 5 years retrospectively
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
Hashimoto thyreoditis %
hypothyreosis %
hyperthyreosis %
antiphospholypid syndrome 0.2 %
MGUS %
all anti-AchR positive
Hodgkin lymphoma 1 patient
post-irradiation sarcoma?
anti-MuSK positive
anti-TPO 1 %
anti-TG %
all anti-AchR positive

16. anti-MuSK n=4 sex all female age at diagnosis EOM LOM 3 75 % 1 25 %
3 75 %
1 25 %
serology
anti-AchR
anti-Titin
anti-MuSK
none 0 %
all %
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