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Prof Ariyanto Harsono MD PhD
SpA(K)
1
Prof Ariyanto Harsono MD, PhD, SpA(K)
Prof Ariyanto Harsono MD PhD
SpA(K)
2
First developed at St Mary Hospital
London at the end of 19th
century.
Basic Principle: Noon and Freeman
Cornerstone in the management of asthma
and allergic rhinitis
Prof Ariyanto Harsono MD PhD
SpA(K)
3
Tree polen
Prof Ariyanto Harsono MD PhD
SpA(K)
4
Prof Ariyanto Harsono MD PhD
SpA(K)
5
Prof Ariyanto Harsono MD PhD
SpA(K)
6
Bee sting
Prof Ariyanto Harsono MD PhD
SpA(K)
7
Dermatophagoides pterisynus
Prof Ariyanto Harsono MD PhD
SpA(K)
8
Dermatophagoides farinai
Prof Ariyanto Harsono MD PhD
SpA(K)
9
The main allergen is the feces of mite
Prof Ariyanto Harsono MD PhD
SpA(K)
10
Transepithelial
delivery
Indirect proteolysis
of TJ protein
Direct proteolysis
of TJ protein
Der p1/Der f1 Der p1/Der f1 Der p1/Der f1
Prof Ariyanto Harsono MD PhD
SpA(K)
11
Atopy
Prof Ariyanto Harsono MD PhD
SpA(K)
12
allergen
2004: 3:234-237
Allergy Allergy
Grow out
Allergen
Exposure
Allergen IT
Prof Ariyanto Harsono MD PhD
SpA(K)
13
TLR 1,2,6,7,8,11
Respon imun melawan infeksi
faktor-faktor yang mempengaruhi respon
Subset Dendritic Cell
Subset DC1
IL-12
Nat Rev Immunol, 2003,3:984-93
Prof Ariyanto Harsono MD PhD
SpA(K)
Prof Ariyanto Harsono MD PhD
SpA(K)
14
Respon imun melawan infeksi
faktor-faktor yang mempengaruhi respon
Subset Dendritic Cell
Subset DC2
TLR 1,4,7,9,10
IL-13
Nat Rev Immunol, 2003,3:984-93
Prof Ariyanto Harsono MD PhD
SpA(K)
Prof Ariyanto Harsono MD PhD
SpA(K)
15
2004: 3:234-237
Allergen exposureAllergen IT
Prof Ariyanto Harsono MD PhD
SpA(K)
16
Pre Immunotherapy Post Immunotherapy
J Allergy Clin Immunol 2004 • Volume 113 • Number 6 :1234-1237
Prof Ariyanto Harsono MD PhD
SpA(K)
17
Prof Ariyanto Harsono MD PhD
SpA(K)
Prof Ariyanto Harsono MD PhD
SpA(K)
18
Allergen exposure
IL-4, IL-5
IL-13
Th-2 Cell
IL-13
B Cell
Prof Ariyanto Harsono MD PhD
SpA(K)
19
IgG
Allergen IT
Th-1 CellIL-12 IFN-γ
IL-2
B Cell
Prof Ariyanto Harsono MD PhD
SpA(K)
20
Pre Immunotherapy Post Immunotherapy
J Allergy Clin Immunol 2004 • Volume 113 • Number 6 :1234-1237
Prof Ariyanto Harsono MD PhD
SpA(K)
21
:
Pre Immunotherapy
Post Immunotherapy
J Allergy Clin Immunol 2004 • Volume 113 • Number 6 :1234-1237
IFN-γ
Prof Ariyanto Harsono MD PhD
SpA(K)
Prof Ariyanto Harsono MD PhD
SpA(K)
22
Pre Immunotherapy
Post Immunotherapy
J Allergy Clin Immunol 2004 • Volume 113 • Number 6 :1234-1237
23
Other study…
Durham 1998, reported
reduce of IL-4 and IL-5;
increase of IFN-γ and
IL-2 as well as reduce
of IgE and increase IgG
resulted in the diminish
late phase reaction
(JACI 1998;102:157-64)
IL-2
Prof Ariyanto Harsono MD PhD
SpA(K)
Prof Ariyanto Harsono MD PhD
SpA(K)
24
2004: 3:234-237
Prof Ariyanto Harsono MD PhD
SpA(K)
25
2004: 3:234-237
Prof Ariyanto Harsono MD PhD
SpA(K)
Prof Ariyanto Harsono MD PhD
SpA(K)
26
Th-2 Th-2
Th-1 Th-1
Atopic Patient
Allergen IT treated
Atopic Patient
(Guerra. JACI 2001;107:647-53)
Prof Ariyanto Harsono MD PhD
SpA(K)
27
(Akdis, J Clin Invest 1998;102:98-106)
Prof Ariyanto Harsono MD PhD
SpA(K)
Prof Ariyanto Harsono MD PhD
SpA(K)
28
Allergen extract:-Whole body extract
-Pure venom extract
10% residual risk
Prof Ariyanto Harsono MD PhD
SpA(K)
29
•Effective in Seasonal allergic rhinitis
•Less effective in perennial allergic rhinitis
•Mark improvement in tolerance of cat
exposure
Prof Ariyanto Harsono MD PhD
SpA(K)
30
•Common indication in North America and
Europe
•Meta analysis 1954-1998: beneficial effect
•DBPC: 60-75% reduce of symptom score in
patients with grass pollen allergy
•Economic analysis: less cost than pharmaco-
therapy
31
GROUP
ControlSub-cutan ITSub-lingual IT
Mean
18
16
14
12
10
8
6
PEFR Variability Pre
(%)
PEFR Variability Pos
t (%)
Study from Surabaya
(Harsono. Fol Med Indones 2003;39:223-7)
Prof Ariyanto Harsono MD PhD
SpA(K)
32
IL-12
IL-5IL-4
IL-13
Immunotherapy
µ−>γ
IgE IgG
Asthma symptom
(Rev FEV-1)
Asthma symptom
(Rev FEV-1)
Cortikosteroid
IFN-γ IL-2
µ−>ε
/
/
Group A
Group B
Group C
Study from Surabaya
(Harsono, Dissertation 2004)
Prof Ariyanto Harsono MD PhD
SpA(K)
Prof Ariyanto Harsono MD PhD
SpA(K)
33
-5
0
5
10
15
Group A Group B Group C
IL_5
IL_2
Reduced of IL-5 correlate with significant increased of IL-2
Analysis of discriminant
Prof Ariyanto Harsono MD PhD
SpA(K)
34
The improvement of FEV-1 reversibility is a
cumulative result of 4 factors
• decreased IL-4, enhances inhibition of IgE production.
• decreased IL-5, enhances inhibition of eosinophil
maturation in the stem cell, chemo taxis, and prolonged life
span.
• increased IFN-γ enhances isotype switching of
immunoglobuline production in favor of IgG subclass
instead of IgE.
• increased IL-2 enhances the affinity maturation and
differentiation of B cells giving rise to the generation of B
memory cells and antibody secreting plasma cells
producing IgG.
Prof Ariyanto Harsono MD PhD
SpA(K)
35
Conclusion
 Immunotherapy in asthmatic children
results in elevation of IFN-γ and IL-2, diminish
IL-4 and IL-5.
 Addition of inhaled corticosteroid to
immunotherapy results in marked attenuation
of IL-5 correlates with greater elevation of
IL-2 and play an important role in the
modulation of immune response resulting in
the improvement of FEV-1 reversibility.
Prof Ariyanto Harsono MD PhD
SpA(K)
36
•Reduce development of Rhinitis to
asthma
•Reduce developing new sensitization
•Prevent allergic children from going on
to develop asthma
•Rhinitis symptom seem to show more
sustain relief
Prof Ariyanto Harsono MD PhD
SpA(K)
37
UK 1957-1986: 26 fatal cases 17 for
asthma
5-35% systemic reactions for asthma
Contra indications:
•Auto-immune disease
•Malignancy
•Cardiac disease
•Patients receiving beta blocker
Prof Ariyanto Harsono MD PhD
SpA(K)
38
1. The primary mechanism of action is a
shift in the balance of Th-1 and Th-2
cytokine expression in the allergen-
challenged site.
2. Allergen IT is highly form of treatment
of IgE mediated diseases.
3. Highly effective for allergic rhinitis and
hypersensitivity to wasp and bee
venom.
4. Consideration for primary use in
asthma is still controversial in regards
the potential development of adverse
event.
Prof Ariyanto Harsono MD PhD
SpA(K)
39

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Allergen immunotherapy for allergic diseases

  • 1. Prof Ariyanto Harsono MD PhD SpA(K) 1 Prof Ariyanto Harsono MD, PhD, SpA(K)
  • 2. Prof Ariyanto Harsono MD PhD SpA(K) 2 First developed at St Mary Hospital London at the end of 19th century. Basic Principle: Noon and Freeman Cornerstone in the management of asthma and allergic rhinitis
  • 3. Prof Ariyanto Harsono MD PhD SpA(K) 3 Tree polen
  • 4. Prof Ariyanto Harsono MD PhD SpA(K) 4
  • 5. Prof Ariyanto Harsono MD PhD SpA(K) 5
  • 6. Prof Ariyanto Harsono MD PhD SpA(K) 6 Bee sting
  • 7. Prof Ariyanto Harsono MD PhD SpA(K) 7 Dermatophagoides pterisynus
  • 8. Prof Ariyanto Harsono MD PhD SpA(K) 8 Dermatophagoides farinai
  • 9. Prof Ariyanto Harsono MD PhD SpA(K) 9 The main allergen is the feces of mite
  • 10. Prof Ariyanto Harsono MD PhD SpA(K) 10 Transepithelial delivery Indirect proteolysis of TJ protein Direct proteolysis of TJ protein Der p1/Der f1 Der p1/Der f1 Der p1/Der f1
  • 11. Prof Ariyanto Harsono MD PhD SpA(K) 11 Atopy
  • 12. Prof Ariyanto Harsono MD PhD SpA(K) 12 allergen 2004: 3:234-237 Allergy Allergy Grow out Allergen Exposure Allergen IT
  • 13. Prof Ariyanto Harsono MD PhD SpA(K) 13 TLR 1,2,6,7,8,11 Respon imun melawan infeksi faktor-faktor yang mempengaruhi respon Subset Dendritic Cell Subset DC1 IL-12 Nat Rev Immunol, 2003,3:984-93 Prof Ariyanto Harsono MD PhD SpA(K)
  • 14. Prof Ariyanto Harsono MD PhD SpA(K) 14 Respon imun melawan infeksi faktor-faktor yang mempengaruhi respon Subset Dendritic Cell Subset DC2 TLR 1,4,7,9,10 IL-13 Nat Rev Immunol, 2003,3:984-93 Prof Ariyanto Harsono MD PhD SpA(K)
  • 15. Prof Ariyanto Harsono MD PhD SpA(K) 15 2004: 3:234-237 Allergen exposureAllergen IT
  • 16. Prof Ariyanto Harsono MD PhD SpA(K) 16 Pre Immunotherapy Post Immunotherapy J Allergy Clin Immunol 2004 • Volume 113 • Number 6 :1234-1237
  • 17. Prof Ariyanto Harsono MD PhD SpA(K) 17 Prof Ariyanto Harsono MD PhD SpA(K)
  • 18. Prof Ariyanto Harsono MD PhD SpA(K) 18 Allergen exposure IL-4, IL-5 IL-13 Th-2 Cell IL-13 B Cell
  • 19. Prof Ariyanto Harsono MD PhD SpA(K) 19 IgG Allergen IT Th-1 CellIL-12 IFN-γ IL-2 B Cell
  • 20. Prof Ariyanto Harsono MD PhD SpA(K) 20 Pre Immunotherapy Post Immunotherapy J Allergy Clin Immunol 2004 • Volume 113 • Number 6 :1234-1237
  • 21. Prof Ariyanto Harsono MD PhD SpA(K) 21 : Pre Immunotherapy Post Immunotherapy J Allergy Clin Immunol 2004 • Volume 113 • Number 6 :1234-1237 IFN-γ Prof Ariyanto Harsono MD PhD SpA(K)
  • 22. Prof Ariyanto Harsono MD PhD SpA(K) 22 Pre Immunotherapy Post Immunotherapy J Allergy Clin Immunol 2004 • Volume 113 • Number 6 :1234-1237
  • 23. 23 Other study… Durham 1998, reported reduce of IL-4 and IL-5; increase of IFN-γ and IL-2 as well as reduce of IgE and increase IgG resulted in the diminish late phase reaction (JACI 1998;102:157-64) IL-2 Prof Ariyanto Harsono MD PhD SpA(K)
  • 24. Prof Ariyanto Harsono MD PhD SpA(K) 24 2004: 3:234-237
  • 25. Prof Ariyanto Harsono MD PhD SpA(K) 25 2004: 3:234-237 Prof Ariyanto Harsono MD PhD SpA(K)
  • 26. Prof Ariyanto Harsono MD PhD SpA(K) 26 Th-2 Th-2 Th-1 Th-1 Atopic Patient Allergen IT treated Atopic Patient (Guerra. JACI 2001;107:647-53)
  • 27. Prof Ariyanto Harsono MD PhD SpA(K) 27 (Akdis, J Clin Invest 1998;102:98-106) Prof Ariyanto Harsono MD PhD SpA(K)
  • 28. Prof Ariyanto Harsono MD PhD SpA(K) 28 Allergen extract:-Whole body extract -Pure venom extract 10% residual risk
  • 29. Prof Ariyanto Harsono MD PhD SpA(K) 29 •Effective in Seasonal allergic rhinitis •Less effective in perennial allergic rhinitis •Mark improvement in tolerance of cat exposure
  • 30. Prof Ariyanto Harsono MD PhD SpA(K) 30 •Common indication in North America and Europe •Meta analysis 1954-1998: beneficial effect •DBPC: 60-75% reduce of symptom score in patients with grass pollen allergy •Economic analysis: less cost than pharmaco- therapy
  • 31. 31 GROUP ControlSub-cutan ITSub-lingual IT Mean 18 16 14 12 10 8 6 PEFR Variability Pre (%) PEFR Variability Pos t (%) Study from Surabaya (Harsono. Fol Med Indones 2003;39:223-7) Prof Ariyanto Harsono MD PhD SpA(K)
  • 32. 32 IL-12 IL-5IL-4 IL-13 Immunotherapy µ−>γ IgE IgG Asthma symptom (Rev FEV-1) Asthma symptom (Rev FEV-1) Cortikosteroid IFN-γ IL-2 µ−>ε / / Group A Group B Group C Study from Surabaya (Harsono, Dissertation 2004) Prof Ariyanto Harsono MD PhD SpA(K)
  • 33. Prof Ariyanto Harsono MD PhD SpA(K) 33 -5 0 5 10 15 Group A Group B Group C IL_5 IL_2 Reduced of IL-5 correlate with significant increased of IL-2 Analysis of discriminant
  • 34. Prof Ariyanto Harsono MD PhD SpA(K) 34 The improvement of FEV-1 reversibility is a cumulative result of 4 factors • decreased IL-4, enhances inhibition of IgE production. • decreased IL-5, enhances inhibition of eosinophil maturation in the stem cell, chemo taxis, and prolonged life span. • increased IFN-γ enhances isotype switching of immunoglobuline production in favor of IgG subclass instead of IgE. • increased IL-2 enhances the affinity maturation and differentiation of B cells giving rise to the generation of B memory cells and antibody secreting plasma cells producing IgG.
  • 35. Prof Ariyanto Harsono MD PhD SpA(K) 35 Conclusion  Immunotherapy in asthmatic children results in elevation of IFN-γ and IL-2, diminish IL-4 and IL-5.  Addition of inhaled corticosteroid to immunotherapy results in marked attenuation of IL-5 correlates with greater elevation of IL-2 and play an important role in the modulation of immune response resulting in the improvement of FEV-1 reversibility.
  • 36. Prof Ariyanto Harsono MD PhD SpA(K) 36 •Reduce development of Rhinitis to asthma •Reduce developing new sensitization •Prevent allergic children from going on to develop asthma •Rhinitis symptom seem to show more sustain relief
  • 37. Prof Ariyanto Harsono MD PhD SpA(K) 37 UK 1957-1986: 26 fatal cases 17 for asthma 5-35% systemic reactions for asthma Contra indications: •Auto-immune disease •Malignancy •Cardiac disease •Patients receiving beta blocker
  • 38. Prof Ariyanto Harsono MD PhD SpA(K) 38 1. The primary mechanism of action is a shift in the balance of Th-1 and Th-2 cytokine expression in the allergen- challenged site. 2. Allergen IT is highly form of treatment of IgE mediated diseases. 3. Highly effective for allergic rhinitis and hypersensitivity to wasp and bee venom. 4. Consideration for primary use in asthma is still controversial in regards the potential development of adverse event.
  • 39. Prof Ariyanto Harsono MD PhD SpA(K) 39

Editor's Notes

  1. Ariyanto Harsono-Imunopathogenesisi of CMA