myasthenia gravis among hungarians
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Myasthenia gravisamong Hungarians
Department of NeurologyUniversity of Pecs
Zsolt Illes
Pécs
225 samples• sera• DNA• clinical data
• 225 analyzed for anti-AchR antibodies• 149 analyzed for anti-Titin antibodies• 36 analyzed for anti-MuSK antibodies
database and tissue bank at Pecs
• University of Pecs, Department of Neurology, Pecs• Jahn Ferenc Teaching Hospital, Department of Neurology, Budapest
Pécs Budapest
sex ratio
n=225
0
20
40
60
80
100
n147
n78
Perc
en
tag
e
F M
0
19
40
2124
2825
16
2
0
5
10
15
20
25
30
35
40
45
1-10 11-20 21-30 31-40 41-50 51-60 61-70 71-80 81-
age (years)
age at the time of diagnosis
n=175mean age: 44.6
years
num
ber
of
pati
en
ts
age at the time of diagnosis: females
n=109mean age: 37.7
years
0
18
36
1613
11
68
10
5
10
15
20
25
30
35
40
num
ber
of
pati
en
ts
1-10 11-20 21-30 31-40 41-50 51-60 61-70 71-80 81-
age (years)
64%
age at the time of diagnosis: males
0 1 4 5
11
1719
8 10
5
10
15
20
1-10 11-20 21-30 31-40 41-50 51-60 61-70 71-80 81-
n=66mean age: 56.1
years
num
ber
of
pati
en
ts
age (years)
68%
anti-AchR antibody
anti-AchR positiveanti-AchR negative
20
40
60
80
100
141 34
n=175
number of patients
perc
en
tag
e
total
80.6
19.4
84 25
n=109
female
number of patients
77.1
22.913.6
57 9
n=66
male
number of patients
86.4
anti-Titin antibody
anti-titin positiveanti-titin negative
n=149
total
35 114number of patients
20
40
60
80
100
perc
en
tag
e
23.5
76.5
14.9
n=94
female
14 80number of patients
85.1
n=55
male
21 34number of patients
61.8
38.2
+-
anti-AchR
combination of antibodies
175 patientsanti-AchR+: 141 80.6%anti-AchR-: 34 19.4%
149 patientsanti-AchR+: 117 79%anti-AchR-: 32 21%
anti-Titin32/117
anti-MuSK0/23
0
20
40
60
80
100
27% 0%
+
9%0
20
40
60
80
100
anti-Titin3/32
anti-MuSK4/13
-
31%
+-
combination of antibodies
anti-Titin149 patientsanti-Titin+: 114 23.5%anti-Titin-: 35 76.5%
91%
anti-AchR32/35
anti-MuSK0/7
0
20
40
60
80
100
0%
+
14%
74%
0
20
40
60
80
100
anti-AchR85/114
anti-MuSK4/29
-
0.94 [0.42-2.12]
0.8859 (89)7 (11)26 (79)7 (21)0(0)33Thymoma
1.07 [0.53-2.15]0.8474 (88)10
(12)33 (79)8 (19)1(2)42anti-AchR -
1.46 [1.00-2.12]<0.05277 (84)51 (16)115 (70)47 (29)2(1)164anti-AchR +
1.17 [0.78-1.75]
0.4265 (87)
39 (13)
115 (76)35 (23)2(1)152anti-Titin -
2.10 [1.23-3.58]0.00579 (79)21 (21)30 (60)19 (38)1(2)50anti-Titin +
1.39 [0.98-1.97]0.07354 (85)
62 (15)
149 (72)56 (27)3
(1)208No thymoma
673 (89)85 (11)299 (79)75 (20)5 (1)379Control
[95% CI]C (%)T (%)CCCTTT
ORP Allele
frequencyGenotypen
genetic heterogeneity: PTPN22
Greve et al, Hum Immunol, 2009
genetic heterogeneity
0
4
8
12
16
20
control AchR– Titin+
11.6
1.74.3
total
12.2
min
or
alle
le f
req
uen
cy
16.8
DRB1*1501
MG MS
ICOS-PE
010
110
210
310
410
CD
8-A
PC
010
110
210
310
410 0,24%
wt
ICOS-PE
010
110
210
310
410
CD
8-A
PC
010
110
210
310
410 1,24%1,24%
minor
ICOS
generalization over 5 years:
II: 76 %III: 17 %
IV: 7 %
I: all 100%MGFA at diagnosis
12.4 months
4.7 monthstime to diagnosis
79 %21 %
77 %23 %
anti-AchR: AchR
+ AchR -
24 %41 %male (LOMG)
76 %59 %female (EOMG)
56%44 %percentage of patients
limbocular onset
83 %
ocular vs generalized: 5 years retrospectively
n=71
therapy• thymoma
• hyperplasia
complete remission
• thymoma• hyperplasia
pathology• thymoma
• hyperplasia
23 months (2-132)time to operation
23 %77 %
serology• anti-AchR+• anti-AchR-• anti-MuSK• anti-Titin
24 years (11-56)age at diagnosis
thymectomy
sex
0.07 %0 %
31 %69 %
75 %55 %
all female
pyr (30%) / AZA (30%) / AZA+pyr (30%)nothing (20%) /pyr (40%) /AZA (40%)
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
anti-MuSKn=4
all femalesex
3 75 %1 25 %
age at diagnosis• EOM• LOM
none 0 %none 0 %all 4 100 %
serology• anti-AchR• anti-Titin• anti-MuSK
all bulbar symptoms
all 11 crisis and 13 PE during 7 years 3 crisis and 4 PE during 4 years
crisis
paraneoplasia in one?
acknowledgement
University of TübingenBernhard Greve, Arthur Melms
University of Pecs, HungaryCsilla Rozsa, Samuel Komoly, Renata Vegh, Blanka Kellermayer,
Miklos Banati
Oxford UniversityAngela Vincent
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