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