myasthenia gravis among hungarians
DESCRIPTION
Myasthenia gravis among Hungarians. Zsolt Illes. Department of Neurology University of Pecs. Pécs. 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 - PowerPoint PPT PresentationTRANSCRIPT
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