ЭФФЕКТИВНОСТЬ И МЕХАНИЗМЫ СУБЛИНГВАЛЬНОЙ

»
616.2-056.3-085.37.032.313-036.8.1
14.03.09 –
,
2014
»
,
,
,
,
:
«
»
,
,
:
,
«
»
,
,
,
,
«
»
,
,
,
«
»
«
»
:
23
03.18.04
13.00
»
220116,
rector@bsmu.by;
,
.
,
:
, 83, e-mail
(017) 272-55-98.
«
»
«____»
2014
,
,
.
.
(Papadopoulos N.G., 2012).
150
(
)
(
,
J., 2010).
,
600
.
20%
10
,
200
–
(Canonica G.W., 2009).
(
):
30%
(Bousquet
300
–
).
,
10
(Canonica G.W., 2009).
,
,
.
.
,
,
.
,
,
,
,
,
,
,
.
(
)
.
.
,
.
,
,
,
.
1
.
,
,
(Akdis M., 2009).
.
01.07 «
»
«
»,
,
– 2010–2012
20110048,
.
«
»
2007–2010
.
:
.
:
1.
.
2.
2
,
.
3.
.
4.
.
5.
-4, T
-ß,
-1 A.
6.
.
: 90
, 60
(
–
,
),
.
in vivo
30
in vitro;
174
,
(
).
:
; 74
.
,
;
,
IgE,
IgG4
(
:
-4,
-5,
-10,
-13,
: T-bet, GATA-3, ROR- t);
-4
-589,
+874,
-1 A;
,
in vivo
);
in vitro (
,
-17,
T
;
-ß
(
3
-509,
).
,
:
1.
.
,
–
,
,
.
2.
,
,
.
Penicillium, Cladosporium, Aspergillus, Ulocladium.
,
,
.
3.
IgE
IgG4
IgE/IgG4
.
,
.
4.
Th2
-4,
-5,
Th17 (
Th1
-13
),
-17),
Tregs-1,
,
-10.
-13
.
Th17
,
,
.
5.
,
IgE
-589
(
3,50 IU/ml)
,
-4
.
6.
c
.
4
.
,
,
.
,
,
.
«10-
», «2.
»,
.
,
in vivo
in vitro,
,
,
.
«
.
,
10»
,
.
,
:
–
(
.
)
.,
«
»;
–
10;
.
–
.
,
,
,
;
,
.
.
,
,
.
,
,
,
,
5
,
.
,
,
,
,
,
.
,
,
[1],
,
[2, 3, 4, 5, 7, 21, 23, 24],
[28, 31, 35, 36, 40] –
,
95%.
,
[1], c
[28, 30],
[6, 10],
[52, 56] –
,
[1],
[9, 12, 27],
[33, 37, 38, 39],
,
95%.
,
[48, 53, 55] –
90%.
[11];
–
,
[1],
–
[38, 39, 42];
,
[22];
[1],
,
–
[13] –
90%.
[1], c
[8, 10, 16, 17, 18, 19, 20, 25, 26],
–
– [15, 16, 17, 18, 19, 20, 24, 26],
,
,
[29, 30, 32, 34, 36, 41],
[43, 44, 45, 47, 49, 51, 54,
95%.
[1],
[14],
[50] –
90%.
[1],
56] –
-4
[1] –
5, 6, 7, 8, 10, 16, 18, 20, 26],
[29, 30, 31, 32, 36],
95%.
,
95%.
[1],
,
,
[43, 44, 45, 46, 54, 56] –
.
[59] –
6
80%.
[4,
2
58] –
,
[57,
85%.
.
(
,
, 2010); 27(
«
,
,
, 2010);
» (
,
2010);
» (
, 2010);
«
,
,
» (
(
,
, 2010);
, 2011);
«
»(
,
, 2011); Annual Scientific
Meeting the American College of Allergy, Asthma & Immunology (Boston, USA,
2011); EAACI-WAO World Allergy & Asthma Congress (Istanbul, urkey, 2011);
«
»
,
, 2012); European Academy of Allergy and Clinical
Immunology Congress (Geneva, Switzerland, 2012); Congress American
Academy of Allergy, Asthma & Immunology (Orlando, USA, 2012); International
Food Allergy Conference (Anaheim, USA, 2012);
(
,
,
2013); I
«
»(
,
, 2013); III
,
, 2013); EAACI-WAO World Allergy & Asthma Congress
(Milan, Italy, 2013);
-2013» (
,
, 2013);
«
» (
,
, 2013);
«
» (
,
, 2013); Annual Meeting of the American College of Allergy, Asthma
& Immunology (Baltimore, USA, 2013);
2013
2014
(
,
, 2013).
.
56
: 1
(10,5
); 21
,
18
7
,
1
(9,73
2–
–
),
; 6
), 15
,
(0,79
27,06
14 –
(1,59
,
(4,45
).
.
), 14
–
2
,
.
.
198
).
(
,
,
430
,
236
,
,
,
(194
), 56
.
44
63
.
.
–
,
.
.
–
–
-
2.
.
.
,
174
,
(
).
,
,
,
8
74
.
.
(
, «
»,
)
.
IgE
(R-Biopharm,
«10-
)
».
(n=60)
IgE
min
(Sevapharma,
2
.
3 (3,50–17,49 IU/ml)
).
1 (n=30)
:
(17
)
(13
).
1
2 (n=30)
,
,
,
,
.
.
(17
,
–
1
).
13
–
15
,
15 –
.
.
:
.
(
:
) –
(
)–
.
«
»
2.
)
CD127–), CD69+
Dickenson,
Weasel
(R&D,
:
(CD45+CD3–CD16+56+),
,
+
HLA-DR
)
3.0 (WEHI,
,
(CD4+
.
FACSCalibur (Becton
CellQuest 3.3
).
CD4+
),
9
(R&D,
,
,
,
high
CD25
,
:
CD4
-4,
-5,
-13,
-17
.
T-bet, GATA-3
CD4+
(
+
ROR- t,
Th1-, Th2-
Th17-10
»)
.
«10-
«
«
»,
,
-10-
»
).
IgG4
«10-
(
ELISA (DR.FOOKE,
»)
).
2IgE
:
.
,
-1
,
-4,
-ß
«
».
9
)
30
19
36
(21
,
,
,
(in vivo
in vitro)
.
.
(Asthma Control Test –
).
.
,
.
)
Statistica
7 8 (StatSoft,
11
12 (Microsoft,
).
Microsoft Office Excel
W-
.
,
.
Me (25–75),
2575-
Me –
,
25
75 –
.
U-
– W-
,
.
10
2
.
.
(R).
,
(
)
0,05.
.
,
5
25%.
50%
.
70%.
,
16%,
– 17%,
571
– 15%.
100
,
5
(2005–2010 .)
.
697 ( 22%).
5
2020 .
,
.
100 000
2012 .
0,79%
.
.
.
5–10
.
.
10
,
–
30–40
.
,
70%.
26,7%
15,2% –
.
2012 .
,
, 58,1% –
.
33,7%
,
13 150
.
,
,
60 872
.
.
2012 .
1400
).
,
.
11
,
74 022
(804 –
596 –
2%
2
11
.
1 (30
.
,
,
)
19
.
(25–33)
,
(Me,
(Me, 25–75%)
(Me, 25–75%)
25–75%)
30,5
– 9,5 (5–16)
5,0 (1,0–13,0)
13
.
.
.
(43%).
20
–
;
;
6
,
–
4
.
6
.
.
.
2 (30
(Me, 25–75%)
)
20
.
10
28 (22–35)
.
13
(43%).
(Me, 25–75%)
(Me, 25–75%)
,
,
,
12 (6–16)
9,0 (3,0–12,0)
15
.
.
11
4
.
5
,
.
6
–
,
.
( 17 –
,
13
–
).
,
.
15
.
15
,
in vivo in vitro.
174
in vivo
,
,
in vitro
59
(33,9%),
18%
Ig E
.
(16,7%)
12
,
.
(19%)
.
33
,
,
21
(12%).
6
(28,6%),
15
,
.
,
.
30
(23,0–29,0)
(70%).
25,5
(Me, 25–75%).
9
(30%)
21
.
74
.
,
,
35
(47,3%).
9
(25,7%)
.
3
(8,6%)
.
8
(22,8%).
,
,
,
16
(21,6%).
14
(18,9%).
9
3
(33,3%)
.
(12,2%).
3
(33,3%)
,
,
.
2
,
,
.
,
.
24
(32%)
13
28 (38%)
22
,
(30%)
.
,
,
.
,
.
Aspergillus
Penicillium,
Aspergillus.
Penicillium
.
,
18%
82%
500 1
500 1
3
3
.
,
.
500
1 3
Aspergillus niger, Aspergillus versicolor, Penicillium cyclopium, Cladosporium
cladosporioides.
,
500
1 3
Alternaria alternata, Chaetomium globosum, Stachybotrys
chartarum, Ulocladium chartarum.
,
74
.
.
Penicillium (56,8%), Cladosporium (48,6%), Aspergillus
(37,8%), Ulocladium (19,0%).
Stemphylium (5,4%), Stachibotrys (4,0%), Verticillium (4,0%), Chaetomium
(2,7%), Statibotrys (2,7%), Trichoderma (1,4%).
.
1.
.
Penicillium, Cladosporium, Ulocladium,
,
(98%)
,
,
.
Aspergillus,
.
,
14
1
2
,
.
60,0%
56,8%
48,6%
50,0%
37,8%
40,0%
30,0%
19,0%
20,0%
10,0%
5,4%
4,0%
4,0%
2,7%
2,7%
1,4%
Pe
ni
cil
liu
m
Cl
ad
sp
os
.
po
riu
m
sp
.
As
pe
rg
ill
us
Ul
cla
di
um
St
em
ph
yl
iu
m
St
ac
hi
bo
tr
ys
Ve
rti
cil
liu
m
Ch
ae
to
m
iu
m
St
at
ib
ot
ry
s
Tr
ich
od
er
m
a
0,0%
1–
.
IgE
.
IgE
3 (3,50–17,49 IU/ml).
17
IgE
9,20 (6,28–16,22) IU/ml
.
13
(W6)
(Me, 25–75%)
1
(Gx)
(Me, 25–75%)
(Me, 25–75%) 3,4 (3,1–3,9)
IgE
(Me, 25–75%) 15,85 (7,44–100,0) IU/ml
3,8 (3,2–6,0)
.
17
1
–
.
17
2
IgE
(Gx)
(Me, 25–75%) 11,76 (6,59–31,62) IU/ml,
(Me, 25–75%) 3,5 (3,2–4,4)
.
13
15
13
IgE
(Me, 25–75%) 11,06 (4,42–100,0) IU/ml,
3,5 (3,0–6,0)
.
2
(W6)
(Me, 25–75%)
.
Penicillium
15
2
IgE
notatum (M1)
(Me, 25–75%) 6,41 (5,05–13,21) IU/ml
(Me, 25–75%) 3,2 (3,1–3,6)
.
IgE
Aspergillus fumigatus (M3)
2
(Me, 25–75%)
4,95 (4,44–10,27) IU/ml
(Me, 25–75%) 3,1 (3,0–3,4)
.
15
IgE
Dermatophagoides pteronyssinus (D1)
(Me, 25–75%) 16,60 (8,08–36,72) IU/ml,
(Me, 25–75%)
3,9 (3,3–4,5)
,
IgE
Dermatophagoides farinae (D2): (Me, 25–75%)
10,07 (4,39–43,92) IU/ml
(Me, 25–75%) 3,4 (3,0–4,8)
.
,
,
.
:
,
15
,
15 –
.
.
1
2,
2–
3.
Alternaria alternata (M6)
Aspergillus fumigatus (M3)
Cladosporium herbarum (M2)
Penicillium notatum (M1)
( 82)
( 84)
( 6)
–
( 5)
–
( 3)
( 1)
–
(W9)
(G12)
–
( 7)
–
( 4)
–
( 3)
–
( 2)
Dermatophagoides farinae (D2)
5
7
7
3
4
7
4
8
6
11
8
20
8
11
14
14
11
0
5
10
2–
15
20
25
1
16
13
Alternaria alternata (M6)
Cladosporium herbarum (M2)
14
2
( 82)
8
( 84)
1
( 6)
–
( 5)
–
( 3)
12
7
18
( 1)
–
7
(W9)
20
(G12)
–
( 7)
–
( 4)
–
( 3)
8
18
21
0
5
10
15
3–
20
25
2
1
IgE
Gx (Wilcoxon
W6 (Wilcoxon matched pairs test:
matched pairs test: =0,002)
=0,008).
2
IgE
Gx (Wilcoxon matched pairs test:
=0,0003)
W6 (Wilcoxon matched pairs test: =0,001).
2
IgE
Dermatophagoides pteronyssinus
(Wilcoxon matched pairs test: =0,0006) Dermatophagoides farinae (Wilcoxon
matched pairs test: =0,0006).
IgE
Penicillium notatum
(Wilcoxon matched pairs test: =0,0006)
Aspergillus fumigatus (Wilcoxon
matched pairs test: =0,0006).
IgG4
Gx (Wilcoxon matched
pairs test: =0,0003)
W6 (Wilcoxon matched pairs test: =0,008)
1.
IgE/IgG4
1
Gx,
W6 (Wilcoxon matched pairs test: <0,001).
IgG4
Gx (Wilcoxon matched pairs test: =0,0002)
W6 (Wilcoxon matched pairs test: =0,001), Dermatophagoides
pteronyssinus
Dermatophagoides farinae (Wilcoxon matched pairs test:
17
=0,0006)
2.
IgE/ IgG4
2
Gx
W6,
(Wilcoxon matched pairs test: <0,001).
(Spearman:
1
r=-0,587;
=0,013)
IgG4
IgE
.
IgG4
,
.
,
,
IgG4
,
Ig
IgE/IgG4,
.
.
1
-4 (Mann–Whitney test: z=2,41; =0,01),
-17 (Mann–Whitney test: z=2,79;
=0,005),
-5 (Mann–Whitney test: z=5,17; <0,001)
-13 (Mann–Whitney
test: z=3,50; <0,001).
,
-13
,
(Mann–Whitney test: z=5,16; <0,001).
1
-10
(Mann–Whitney test: z=6,65; <0,001).
GATA-3(Mann–Whitney test: z=3,77; <0,001).
2
(Mann–Whitney test:
z=-0,00; <0,001)
(Mann–Whitney test: z=-2,46; =0,01)
+
+
CD4 HLA-DR
1.
2
-4
(Mann–Whitney test: z=2,40; =0,01)
.
-17
(Mann–Whitney test: z=2,28; =0,02),
,
(Mann–
18
Whitney test: z=3,42;
=0,001).
-5 (Mann–Whitney test: z=3,01; =0,002)
-13 (Mann–
Whitney test: z=3,42; <0,001)
.
,
-13
(Mann–Whitney test: z=5,17; <0,001).
2
-10
(Mann–Whitney
test: z=6,65; <0,001).
GATA-3(Mann–Whitney test: z=2,36; =0,018)
ROR- t(Mann–Whitney test: z=3,48; <0,001).
,
2
ROR- t1 (Mann–Whitney test: z=-3,06;
=0,002).
-4
(Kruskal–Wallis test:
-4
1 (Mann–Whitney test: z=2,41; =0,01),
(Mann–Whitney test: z=2,40; =0,01)
.
-4
1
2
.
1,
=7,80;
2
=0,02).
2
.
-17
(Kruskal–
Wallis
test:
=9,36;
=0,009).
-17
(Mann–Whitney test: z=2,79; =0,005),
(Mann–Whitney test: z=2,28; =0,02)
.
,
-17
.
0,77 (0,51–1,24),
– 0,22 (0,17–0,36).
1
2
-17
-5
Wallis test:
=30,58;
(Kruskal–
-5
<0,001).
19
1 (Mann–Whitney test:
2 (Mann–Whitney test: z=3,01;
.
-5
.
-13
(Kruskal–Wallis
z=5,17; <0,001),
=0,002)
1
test:
=16,09;
2
=0,0003).
1 (Mann–Whitney test: z=3,50; =0,0004)
2 (Mann–Whitney test: z=3,42; =0,0006)
.
,
-13
( <0,001)
,
.
-13
8,18 (6,12–12,90),
–
3,22 (2,25–4,11).
-10
(Kruskal–Wallis test:
=59,56; <0,001).
1 (Mann–Whitney test: z=6,65; <0,001)
2 (Mann–Whitney test: z=6,65; <0,001)
.
T-bet+
(Kruskal–Wallis
test:
GATA-3+
.
=12,75;
=0,001).
GATA-3-
1 (Mann–Whitney test: z=3,77;
(Mann–Whitney test: z=2,36; =0,018)
.
1
2
.
=0,0001)
2
ROR- t-
(Kruskal–Wallis test:
=0,001).
2 (Mann–Whitney test: z=3,48;
.
,
=12,84;
<0,001)
ROR- t2
1 (Mann–Whitney test: z=-3,06; =0,002).
.
20
1
-4 (Wilcoxon matched pairs test: <0,001),
-17 (Wilcoxon matched pairs test: =0,01),
-5 (Wilcoxon matched pairs
test: <0,001),
-13 (Wilcoxon matched pairs test: <0,001)
(Wilcoxon matched pairs test: =0,01).
(Wilcoxon matched pairs test: <0,001)
-10.
1
(Wilcoxon matched pairs test: =0,027)
T-bet,
h1
.
,
GATA-3 (Wilcoxon matched pairs test: <0,027),
h2
.
ROR- t
.
2
-4 (Wilcoxon matched pairs test:
<0,001).
(Wilcoxon matched pairs test: =0,007)
CD4+
-17,
-5 (Wilcoxon matched
pairs test: <0,001),
-13 (Wilcoxon matched pairs test: <0,001).
,
(Wilcoxon
matched pairs test: =0,003)
.
-10
2
(Wilcoxon
matched pairs test: <0,001)
.
2
(Wilcoxon matched pairs test: <0,001)
T-bet
(Wilcoxon matched
pairs test: =0,009)
ROR- t.
GATA-3.
1.
T-bet+
(Kruskal–Wallis test: H=31,25; <0,001).
1 (Mann–Whitney test: z=4,44;
2 (Mann–Whitney test: z=4,98; 2- <0,001).
T-bet+
2
.
21
<0,001)
1
1–
(
1
-4,
(5
, 25–75%)
2
(n=30)
(n=30)
0,30
(0,12–0,50)
0,28
(0,18–0,50)
(n=30)
0,36
(0,13–0,81)
),%
-
18,85
(15,35–24,50)
18,65
15,05
(15,50–25,80) (11,85–19,45)
,
(5
),%
-17,
(5
0,38
(0,14–0,60)
0,20
(0,10–0,38)
0,35
(0,22–0,50)
2,05
(1,15–3.44)
1,88
(1,05–2,55)
1,47
(1,27–1,90)
1,58
(1.20–2,73)
2,06
(1,25–3,13)
1,78
(1,42–2,39)
),%
-5,
(5
),%
-13,
(5
), %
112,65
104,55
163,5
(101,10–138,30) (100,5–107,30) (125,0–226,0)
-10,
– p1-
(test: Kruskal–Wallis, H,
; Mann–Whitney: z, )
H=2,31; =0,31
z=-1,51; 1- =0,13
z=-0,85; 2- =0,39
z=-0,65; 1-2=0,51
H=13,45; =0,001
z=3,15; 1- =0,001
z=3,18; 2- =0,001
z=-0,05; 1-2=0,95
H=4,71; =0,09
z=0,81; 1- =0,41
z=-1,68; 2- =0,09
z=1,91; 1-2=0,05
H=15,16; <0,001
z=-2,65; 1- =0,008
z=-3,75; 2- <0,001
z=1,24; 1-2=0,21
H=12,36; =0,002
z=-3,06; 1- =0,002
z=-3,00; 2- =0,002
z=-0,17; 1-2=0,86
H=59,38; <0,001
z=6,65; 1- <0,001
z=6,65; 2- <0,001
z=0,32; 1-2=0,75
—
1
2
; p2-
—
; p1-2 —
1
GATA-3+
2.
(Kruskal–Wallis test: H=12,74;
=0,001).
=0,0001)
1
2
1 (Mann–Whitney test: z=3,77;
2 (Mann–Whitney test: z=2,36; =0,018).
T-bet+
.
ROR- t+
.
22
2
(Mann–Whitney test: z=-2,49;
=0,012).
.
1
-1 ( -1
(23,33%).
)
: LL – 23 (76,67%),
2/L – 7
2
LL – 20 (66,67%),
2/L – 8
(26,67%),
2/2 – 2 (6,66%).
-1
:
LL – 23 (76,67%),
2/L – 6 (20,0%),
2/2 – 1 (3,3%).
-1
1,
2
.
-1
1
:
L
26
(88,3%),
2* – 4
(11,7%).
2
-1
:
L – 24 (80,0%),
2* – 6
(20,0%).
-1
L – 26 (86,7%),
2* – 4 (13,3%).
2
2*,
,
– 4 (13,3%).
L – 24
(80,0%)
2
,
–
26 (86,7%).
-1
1,
2
.
,
-1
1,
2
.
1
:
AT – 17 (56,7%),
AA – 7 (23,3%),
TT – 6
(20,0%).
2
AT – 17 (56,66%),
AA – 6
(20,00%),
TT – 7 (23,3).
:
– 20 (66,3%),
AA – 4 (13,3%),
TT – 6 (20,0%).
1,
2
.
1:
A – 16 (51,7%),
T – 14 (48,3%).
2
:
A – 14 (48,3%),
T – 16 (51,7%).
23
– 14 (46,7%),
– 16 (53,3%).
-
1,
2
=0,53; p1-2- >0.05).
2
(Chi-square test:
,
1,
+874
2
.
:
-ß
– 16 (53,3%),
– 10 (33,3%),
2
(13,3%).
-ß
(63,3%),
1
TT – 4
– 6 (20,0%),
TT – 5 (16,7%).
-ß
:
TT – 2 (6,6%).
– 14 (46,7%),
– 19
– 14 (46,7%),
-ß
2
1,
.
-ß
1
(60,0%),
T – 12 (40,0%).
-ß
(48,3%).
-ß
(Chi-square test:
– 18
2
:
– 16 (51,7%),
-ß
– 21 (70,0%),
1,
=1,8; p1-2- >0.05).
T – 14
– 9 (30,0%).
2
2
,
-ß
1,
-509
2
.
(33,33%),
(56,7%),
-4
– 19 (63,3%),
2
1
:
TT – 1 (3,4%).
-4
– 25 (83,3%),
– 4 (13,3%),
TT – 1 (3,4%).
-4
:
– 17
– 10 (33,3%),
TT – 3 (10,0%).
=0,04)
2
.
1
(20,0%).
-589
– 10
:
2
24
– 24 (80,0%),
-4
T–6
-4
:
– 27 (90,0%),
22 (73,3%),
T – 3 (10,0%).
-4
– 8 (26,7%).
-4
p1-2- >0.05).
–
1,
2
(Chi-square test:
2
=2,8;
,
-4
-589
(Yates corrected Chi-square2- =3,89; =0,04)
2(
1)
.
-4
–589
.
,
,
-589
,
-4,
,
.
.
1
(Mann–Whitney test: z=-0,05; p=1,00).
2(Wilcoxon matched pairs test:
1,
2.
1
84%,
<0,001)
22 –
1
92%.
2
(Mann–Whitney test: z=0,41; p=0,73).
(Wilcoxon matched pairs test: <0,001)
1,
2.
1
79%,
2 –
88%.
1 (Wilcoxon matched pairs test:
2 (Wilcoxon matched pairs test: <0,001)
.
21
2–
86%.
25
2
<0,001)
83%,
1
2
(Mann–Whitney test: z=0,41; p=0,73).
,
,
(
)
.
2
(72,7%), 3
(27,3%)
6 (100%)
8
.
,
,
,
,
.
:
,
.
,
,
,
,
.
2009–2011
,
,
,
.
,
,
)
1450
,
(
ß2) – 845
.
1
.
2012 .)
(
:
– 500
795
;
(
;
230
– 465
.
,
– 240
.
– 215
,
.
4
,
,
,
,
(
) –
–
,
,
).
,
.
2–3
.
,
26
.
4 798 080 000 000
.
.
,
,
,
.
,
,
,
;
;
,
;
.
,
.
1.
.
50%.
,
2020 .
,
,
5
–
.
,
100 000
2%
[1, 2, 3, 14, 22, 24, 25, 29, 30, 38, 43].
.
2.
.
:
Penicillium (56,8%), Cladosporium (48,6%), Aspergillus (37,8%), Ulocladium
(19,0%).
,
3.
5- (19%)
.
,
.
,
[1, 9, 11, 12, 13, 23, 28, 31, 36, 40, 41, 42, 45, 46, 47].
3.
,
Th1
27
Th2
,
.
,
,
,
.
-13
(Mann–Whitney test: z=5,16; <0,001),
.
,
-17
(Mann–
Whitney test: z=3,42;
=0,001),
[1, 16, 17, 21, 44, 52, 53, 54, 56].
4.
:
h1: T-bet (Wilcoxon matched pairs test: <0,001)
h17
: ROR- t (Wilcoxon
matched pairs test: <0,001),
h2 (
)
h1
-4 (Wilcoxon matched pairs test: <0,001),
-5 (Wilcoxon
matched pairs test: <0,001),
-13 (Wilcoxon matched pairs test: <0,001),
-17 (Wilcoxon matched pairs test: =0,007)
(Wilcoxon
matched pairs test: =0,003).
,
regs, . .
regs-1,
-10,
(Wilcoxon matched pairs
test: <0,001).
,
,
[1, 6, 8, 10, 19, 20, 27, 32, 33, 34, 35, 3739, 48, 49, 50, 51].
5.
,
,
IgE
.
1,
,
IgE
(Wilcoxon matched pairs test: =0,002)
(Wilcoxon matched pairs
28
test:
=0,008).
2,
,
IgE
(Wilcoxon matched pairs
(Wilcoxon matched pairs test: =0,0003)
test: =0,001),
Dermatophagoides pteronyssinus (Wilcoxon matched pairs test: =0,0006)
Dermatophagoides farinae (Wilcoxon matched pairs test: =0,0006),
: Penicillium notatum (Wilcoxon matched pairs test:
=0,0006)
Aspergillus fumigatus (Wilcoxon matched pairs test: =0,0006).
,
IgEIgG.
IgG4
(Wilcoxon matched
pairs test: =0,0003)
W6 (Wilcoxon matched pairs test: =0,008)
1,
.
2,
IgG4
(Wilcoxon
matched pairs test: =0,0002)
(Wilcoxon matched pairs test: =0,001),
Dermatophagoides pteronyssinus Dermatophagoides farinae
(Wilcoxon matched pairs test: =0,0006) [1, 4, 5, 7, 18, 26].
6.
,
IgE/IgG4
1
,
(Wilcoxon matched pairs
test: <0,001).
2
IgE/IgG4
,
(Wilcoxon matched pairs test:
<0,001).
Ig
IgG4
,
,
[1, 18, 26].
7.
-4
-589
2
1)
(Chi-square test:
29
2
=3,89; p2- =0,04).
-4
-589
.
-1
-509
[1, 15, 55].
,
+874,
1,
-ß
2
8.
.
(Wilcoxon-matched pairs test:
<0,001)
1,
2.
1
84%,
2–
1
2
92%.
,
(
,
) [1,
4, 5, 6, 8, 10, 17, 19, 21, 25, 32, 33, 34, 35, 39, 48, 50, 51].
9.
,
,
,
,
,
,
.
4
.
2–3
.
(4798 080000000
.)
[1, 48, 49, 50, 51].
1.
(
,
,
,
,
)
.
[57, 58].
2.
(
-17)
30
-4,
-5,
-13,
,
.
3.
,
.
-13
.
4.
-17
.
5.
,
[58].
6.
IgE/ IgG4
.
7.
-589
-4
,
.
8.
,
,
,
,
.
,
,
,
,
,
[58].
31
,
,
1.
,
/
.
.
2.
.–
,
/
:
, 2012. – 233 .
.
.
//
3.
,
. – 2008. –
4.
,
.
. – 2004. –
.
3. – . 127–131.
.
/
5.
:
.
,
//
. – 2009. –
4. – . 33.
/
.
//
5. – . 131–136.
.
/
. – 2009. –
6.
,
.
//
.
12. – . 64.
.
,
/
. – 2010. – 5. – . 116–120.
7.
,
.
Ars medica. – 2011. – 11. – . 47–52.
8.
,
.
/
.
. 28–32.
9.
,
.
/
.
,
.
. 257–258.
10.
,
.
.
.
/
//
.
//
// Ars medica. – 2011. –
11. –
// Ars medica. – 2011. –
14. –
/
// Ars medica. – 2011. – 14. – . 256–257.
11.
,
.
/
.
,
.
// Ars medica. –
2011. – 11. – . 98–102.
12.
,
.
/
.
,
.
// Ars medica. –
2011. – 11. – . 53–57.
13.
,
.
/
.
,
.
// Ars medica. – 2011. – 11. – . 92–97.
32
14.
.
,
/
// Ars medica. – 2011. –
.
.
,
.
11. – . 103–107.
15.
.
,
.
2011. – 11. – . 40–46.
16.
.
//
17.
,
,
/
.
. – 2012. –
.
.
,
/
// Ars medica. –
.
,
.
4. – . 101–115.
/
.
,
,
,
.
.
,
G4
// Ars
medica. – 2012. – 11. – . 16–20.
18.
,
.
:
/
.
//
Ars medica. – 2012. – 11. – . 30–40.
19.
,
.
-10
/
.
,
.
,
.
// Ars medica. –
2012. – 11. – . 67–72.
20.
,
.
/
.
,
.
,
.
,
.
//
,
. – 2012. – 4. – P. 62–70.
21.
,
.
/
.
,
.
,
.
// Ars medica. – 2012. – 11. – . 61–66.
22.
,
.
/
.
,
.
// Ars medica. – 2012. –
11. –
. 41–46.
23.
,
.
/
.
//
. – 2012. –
3. – . 47–51.
24.
,
.
:
/
.
//
. – 2013. – 3. – . 118–127.
25.
,
.
IgE
/
.
//
.
.
.
. – 2013. –
3. –
. 56–63.
26.
,
.
:
/
.
// I
. – 2013. – 2. – . 2–11.
27. Maslova, L. Fungal contamination of premises as a risk factor for
respiratory allergy / L. Maslova //
.
. – 2013. – 4. – . 23.
33
,
28.
,
,
.
/
.
//
I
27–28
. 2008 . –
29.
,
, .
, 2008. – . 94–99.
.
/
.
.-
.
. 14. – . 250–253.
30.
.
//
,
.,
. 5031.
,
//
., 30
.
:
, 2009. –
. 2009 . –
/
:
.
, 2010 . –
.
., 2010. – . 471–477.
//
2010 . –
..
, 2010. – . 222–224.
.,
.
/
. 2532.
,
,
10,
.
, 27
.
/
.
//
:
.-
.
.,
. 50.
19
. 2010 . –
, 2010. – . 152–155.
33.
,
.
/
.
//
.
.
..
/
.
2011. –
. 17. – . 34–40.
34.
,
.
,
,
:
.
.
.–
.
,
/
.
//
:
.
..
.,
], 12
. 2012
.
.
» ;
, 2012. – . 146–148.
[
,
«
.–
,
.
35.
/
.
.
,
1.
.
.
.
,
.
36.
/
.
..
.,
], 12
. 2012 . /
.
.
.
» ;
, 2012. – . 94–97.
.
. /
.
.
//
.
[
,
«
.–
.
,
.
.
,
D
:
50-
1.
.
. 50-
.
,
.
//
34
.
.
. /
. 117–119.
37.
;
,
.
:
. –
.
., 2012. –
.
/
.
,
.
//
:
..
. 136–139.
38.
./
;
,
.
.
.–
, 2012. –
.
/
.
//
:
.
. 20. – . 85–90.
39.
/
.
/
//
122012. – . 184–185.
40.
.
.
.
,
.
., 2012. –
.
. –
,
.
2012:
.,
,
.
21
2012 . –
, 17–18
,
:
,
D
/
.
.
.
.
.
.
.
,
.
,
.
,
//
:
.
., 2012. – . 81–85.
.–
.
./
;
.
41.
/
.
.
42.
.
//
18–21.07.2013,
.
, 3–4
,
.
,
.
:
, 2013. – . 46.
. 2013 . –
. III
//
.
, .
,
/ .
:
.–
,
.
,
.
, 2013. – . 19–24.
.
,
,
43. Maslova, L.V. Allergen-specific sublingual immunotherapy in season
respiratory allergy symptoms / L.V. Maslova // Alergie. – 2010. – Suppl. 1. –
P. 64. – 27 Sjezd ceskych a slovenskych alergologu a klinickych imunologu s
mezinarodni ucasti, 6–9.10.2010, Olomouc.
35
44. Maslova, L. Allergen-specific sublingual immunotherapy in patients
season respiratory allergy symptoms : abstract
766 / L. Maslova // Allergy. –
2011. – Vol. 66, suppl. s94. – P. 302. – Abstracts of the XXX Congress of
the European Academy of Allergy and Clinical Immunology, Istanbul, Turkey
11–15 June 2011.
45. Titov, L. Allergen-specific sublingual immunotherapy for patients with
grass pollen induced respiratory disease : abstract
764 / L. Titov, L. Maslova,
L. DuBusk // Allergy. – 2011. – Vol. 66, suppl. s94. – P. 302. – Abstracts of
the XXX Congress of the European Academy of Allergy and Clinical
Immunology, Istanbul, Turkey 11–15 June 2011.
46. Titov, L. Clinical Efficacy of Sublingual Immunotherapy in Patients with
Grass Pollen induced Respiratory Allergy Symptoms / L. Titov, L. Maslova,
L.M. DuBuske // Ann. Allergy Asthma Immunol. – 2011. – Vol. 107,
5. –
Annual Meeting of the American College of Allergy, Asthma and Immunology:
Oral and Poster Abstracts 03 November 2011 – 08 November 2011.
47. Th2, Th1 and Th17 cytokine profiles in pollen and mold allergic patients
and healthy subjects / L. Maslova, A. Hancharou, L. Titov, L. DuBuske // Allergy. –
2012. – Vol. 67, suppl. 96. – P. 112.
48. Association of Indoor Mite Allergens and Mold Spores Exposure and
Allergic Respiratory Disease and Asthma in Belarus / L.P. Titov, L.V. Maslova,
T.P. Novikova, L.M. DuBuske // Allergy. – 2012. – Vol. 67, suppl. s96. – A786. –
XXXI Congress of the European Academy of Allergy and Clinical Immunology
Abstract Book, Geneva, Switzerland, 16–20 June 2012.
49. Cytokine status in allergic and healthy individuals / L.V. Maslova,
A.Y. Hancharou, L.P. Titov, L.M. DuBuske // J. Allergy Clin. Immunol. – 2012. –
Vol. 129, 2, suppl. s96. – P. AB214.
50. Interferon-gamma Gene Polymorphism in patients with Allergy /
O.O. Yanovich, L.V. Maslova, L.P. Titov, L.M. DuBuske // J. Allergy Clin.
Immunol. – 2012. – Vol. 129, 2. – . 64.
51. Th2, Th1 and Th17 cytokine profiles in pollen allergic patients before
treatment and after two years of sublingual immunotherapy / L. Maslova,
L.P. Titov, A. Hancharou, L.M. DuBuske // Allergy. – 2012. – Vol. 67, suppl. s96. –
A121. – XXXI Congress of the European Academy of Allergy and Clinical
Immunology Abstract Book, Geneva, Switzerland, 16–20 June 2012.
52.
,
.
in vitro
/
.
// Abstracts of
international scientific conference HEALTH 2013, 20–22 July 2013,
Turkmenistan, Ashgabat. – Ashgabat, 2013. – . 704.
53. Fungal contamination of households as a risk factor for respiratory
allergy / L. Maslova, T. Novikova, L.P. Titov, L.M. DuBuske // Allergy. – 2013. –
36
Vol. 68, suppl. s97. – A173. – Abstracts from the European Academy of Allergy
and Clinical Immunology and World Allergy Organization World Allergy and
Asthma Congress, 22–26 June 2013, Milan, Italy.
54. Maslova, L. Assessment of Efficacy of Allergen Specific sublingual
Immunotherapy in patients with Respiratory Allergic Disease / L. Maslova,
L. Titov, L.M. DuBuske // Ann. Allergy Asthma Immunol. – 2013. – Vol. 111,
5, suppl. A103. – Annual Meeting of the American College of Allergy, Asthma
& Immunology: Oral and Poster Abstracts, 7–11 Nov. 2013.
55. Maslova, L. Fungal contamination of premises as a risk factor
for respiratory allergy / L. Maslova, T. Novikova // Allergy. – 2013. – Vol. 68,
suppl. s97. – A216. – Abstracts from the European Academy of Allergy and
Clinical Immunology and World Allergy Organization World Allergy and Asthma
Congress, 22–26 June 2013, Milan, Italy.
56. Maslova, L. Specific sublingual immunotherapy in respiratory allergy
patients / L. Maslova // Allergy. – 2013. – Vol. 68, suppl. s97. – A185. – Abstracts
from the European Academy of Allergy and Clinical Immunology and World
Allergy Organization World Allergy and Asthma Congress, 22–26 June 2013,
Milan, Italy.
57.
:
118-0912 :
,
.
,
.
,
.
,
.
.
.
12 .
. 28.11.2012 . /
,
.
,
.
.
,
.–
.
,
,
, 2012. –
.
58.
28.11.2012
.
.
.
:
.
/
,
,
.
,
.
,
.
,
.
114-0812 :
,
.
,
.
, 2012. – 6 .
.
.
.–
59.
.
.
,
,
.
.
20121664 ;
.
,
C 12N 1/14 /
.
;
,
. 30.11.2012 ;
. – 2014. –
37
.
.
. 30.06.2014 //
3. – . 21.
:
.
,
.
.
.
./
.
,
,
,
.
.–
.
i
i
i
:
i
,
,
,
,
.
:
.
:
i
,
,
RIDA X SCREEN (R-Biopharm,
),
(MICROS,
),
FACSCalibur
AIF- /340 («
»,
Gene 3000 (
).
i i
,
,
,
41 (Olympus,
(Becton Dickenson,
),
;
50
),
),
Rotor
:
.
.
i
,
.
.
i
i:
;
,
,
,
.
:
,
38
,
,
.
:
,
,
,
,
.
:
.
:
(Olympus,
Dickenson,
,
,
,
; RIDA X SCREEN (R-Biopharm,
50 (MICROS,
),
),
),
AIF- /340
Rotor Gene 3000 (
).
,
,
),
41
FACSCalibur (Becton
(«
»,
),
:
.
.
,
.
.
:
;
,
,
,
.
:
,
.
39
,
,
SUMMARY
Maslova Ludmila
Sublingual immunotherapy of patients with allergic respiratory diseases:
efficacy and mechanisms
Key words: allergic diseases of the respiratory tract, sublingual
immunotherapy, allergen, immune status, polymorphism of genes.
Objective: to develop and implement innovative, integrated technology that
differentiates specific sublingual immunotherapy for allergic respiratory diseases
based on the study of the mechanisms and the effectiveness of its actions.
Research methods and equipment: clinical, electronic-microscopic,
allergic, immunological, genetic, statistical; RIDA X SCREEN (R-Biopharm,
Germany), binocular microscope MS (MICROS, Austria), inverted microscope
SCH (Olympus, Japan), flow cytofluorimeter FACSCalibur (Becton Dickenson,
USA), ELISA analyzer AIF-M/340 («The knight», Belarus), the thermal cycler
Rotor Gene 3000 (Australia).
The obtained results and scientific novelty: defined the features of
the functioning of the immune system in patients with allergic respiratory diseases.
Fungal allergens in the residential areas environment were the first tendecy to be
developed in the Republic of Belarus. The features of the immunological
mechanisms of sublingual immunotherapy are defined. This is the case of home
dust mites when the patients are found with allergie respiratory diseases.
Aninnovative integrated technology was worked out and offered by
the differentiated non-invasive specific immunotherapy of allergie diseases
of the respiratory tract.
Usage Recommendations: diagnosis and prevention of fungal allergies;
effective control of allergic diseases of the respiratory tract caused by sensitization
to pollen, fungal allergens and allergens house dust mites, carried out by
the patients themselves at home.
Application areas: allergology, immunology, therapy, pediatrics.
40
19.11.14.
.
. . 2,32.
.-
60 84/16.
.
«Times».
. . 2,52.
60
.
«
».
593.
:
.
1/187
, 6, 220006,
41
».
,
18.02.2014.
.
,