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Allergen immunotherapy for allergic diseases


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Allergen immunotherapy for allergic diseases

  1. 1. Prof Ariyanto Harsono MD PhDSpA(K)1Prof Ariyanto Harsono MD, PhD, SpA(K)
  2. 2. Prof Ariyanto Harsono MD PhDSpA(K)2First developed at St Mary HospitalLondon at the end of 19thcentury.Basic Principle: Noon and FreemanCornerstone in the management of asthmaand allergic rhinitis
  3. 3. Prof Ariyanto Harsono MD PhDSpA(K)3Tree polen
  4. 4. Prof Ariyanto Harsono MD PhDSpA(K)4
  5. 5. Prof Ariyanto Harsono MD PhDSpA(K)5
  6. 6. Prof Ariyanto Harsono MD PhDSpA(K)6Bee sting
  7. 7. Prof Ariyanto Harsono MD PhDSpA(K)7Dermatophagoides pterisynus
  8. 8. Prof Ariyanto Harsono MD PhDSpA(K)8Dermatophagoides farinai
  9. 9. Prof Ariyanto Harsono MD PhDSpA(K)9The main allergen is the feces of mite
  10. 10. Prof Ariyanto Harsono MD PhDSpA(K)10TransepithelialdeliveryIndirect proteolysisof TJ proteinDirect proteolysisof TJ proteinDer p1/Der f1 Der p1/Der f1 Der p1/Der f1
  11. 11. Prof Ariyanto Harsono MD PhDSpA(K)11Atopy
  12. 12. Prof Ariyanto Harsono MD PhDSpA(K)12allergen2004: 3:234-237Allergy AllergyGrow outAllergenExposureAllergen IT
  13. 13. Prof Ariyanto Harsono MD PhDSpA(K)13TLR 1,2,6,7,8,11Respon imun melawan infeksifaktor-faktor yang mempengaruhi responSubset Dendritic CellSubset DC1IL-12Nat Rev Immunol, 2003,3:984-93Prof Ariyanto Harsono MD PhDSpA(K)
  14. 14. Prof Ariyanto Harsono MD PhDSpA(K)14Respon imun melawan infeksifaktor-faktor yang mempengaruhi responSubset Dendritic CellSubset DC2TLR 1,4,7,9,10IL-13Nat Rev Immunol, 2003,3:984-93Prof Ariyanto Harsono MD PhDSpA(K)
  15. 15. Prof Ariyanto Harsono MD PhDSpA(K)152004: 3:234-237Allergen exposureAllergen IT
  16. 16. Prof Ariyanto Harsono MD PhDSpA(K)16Pre Immunotherapy Post ImmunotherapyJ Allergy Clin Immunol 2004 • Volume 113 • Number 6 :1234-1237
  17. 17. Prof Ariyanto Harsono MD PhDSpA(K)17Prof Ariyanto Harsono MD PhDSpA(K)
  18. 18. Prof Ariyanto Harsono MD PhDSpA(K)18Allergen exposureIL-4, IL-5IL-13Th-2 CellIL-13B Cell
  19. 19. Prof Ariyanto Harsono MD PhDSpA(K)19IgGAllergen ITTh-1 CellIL-12 IFN-γIL-2B Cell
  20. 20. Prof Ariyanto Harsono MD PhDSpA(K)20Pre Immunotherapy Post ImmunotherapyJ Allergy Clin Immunol 2004 • Volume 113 • Number 6 :1234-1237
  21. 21. Prof Ariyanto Harsono MD PhDSpA(K)21:Pre ImmunotherapyPost ImmunotherapyJ Allergy Clin Immunol 2004 • Volume 113 • Number 6 :1234-1237IFN-γProf Ariyanto Harsono MD PhDSpA(K)
  22. 22. Prof Ariyanto Harsono MD PhDSpA(K)22Pre ImmunotherapyPost ImmunotherapyJ Allergy Clin Immunol 2004 • Volume 113 • Number 6 :1234-1237
  23. 23. 23Other study…Durham 1998, reportedreduce of IL-4 and IL-5;increase of IFN-γ andIL-2 as well as reduceof IgE and increase IgGresulted in the diminishlate phase reaction(JACI 1998;102:157-64)IL-2Prof Ariyanto Harsono MD PhDSpA(K)
  24. 24. Prof Ariyanto Harsono MD PhDSpA(K)242004: 3:234-237
  25. 25. Prof Ariyanto Harsono MD PhDSpA(K)252004: 3:234-237Prof Ariyanto Harsono MD PhDSpA(K)
  26. 26. Prof Ariyanto Harsono MD PhDSpA(K)26Th-2 Th-2Th-1 Th-1Atopic PatientAllergen IT treatedAtopic Patient(Guerra. JACI 2001;107:647-53)
  27. 27. Prof Ariyanto Harsono MD PhDSpA(K)27(Akdis, J Clin Invest 1998;102:98-106)Prof Ariyanto Harsono MD PhDSpA(K)
  28. 28. Prof Ariyanto Harsono MD PhDSpA(K)28Allergen extract:-Whole body extract-Pure venom extract10% residual risk
  29. 29. Prof Ariyanto Harsono MD PhDSpA(K)29•Effective in Seasonal allergic rhinitis•Less effective in perennial allergic rhinitis•Mark improvement in tolerance of catexposure
  30. 30. Prof Ariyanto Harsono MD PhDSpA(K)30•Common indication in North America andEurope•Meta analysis 1954-1998: beneficial effect•DBPC: 60-75% reduce of symptom score inpatients with grass pollen allergy•Economic analysis: less cost than pharmaco-therapy
  31. 31. 31GROUPControlSub-cutan ITSub-lingual ITMean181614121086PEFR Variability Pre(%)PEFR Variability Post (%)Study from Surabaya(Harsono. Fol Med Indones 2003;39:223-7)Prof Ariyanto Harsono MD PhDSpA(K)
  32. 32. 32IL-12IL-5IL-4IL-13Immunotherapyµ−>γIgE IgGAsthma symptom(Rev FEV-1)Asthma symptom(Rev FEV-1)CortikosteroidIFN-γ IL-2µ−>ε//Group AGroup BGroup CStudy from Surabaya(Harsono, Dissertation 2004)Prof Ariyanto Harsono MD PhDSpA(K)
  33. 33. Prof Ariyanto Harsono MD PhDSpA(K)33-5051015Group A Group B Group CIL_5IL_2Reduced of IL-5 correlate with significant increased of IL-2Analysis of discriminant
  34. 34. Prof Ariyanto Harsono MD PhDSpA(K)34The improvement of FEV-1 reversibility is acumulative result of 4 factors• decreased IL-4, enhances inhibition of IgE production.• decreased IL-5, enhances inhibition of eosinophilmaturation in the stem cell, chemo taxis, and prolonged lifespan.• increased IFN-γ enhances isotype switching ofimmunoglobuline production in favor of IgG subclassinstead of IgE.• increased IL-2 enhances the affinity maturation anddifferentiation of B cells giving rise to the generation of Bmemory cells and antibody secreting plasma cellsproducing IgG.
  35. 35. Prof Ariyanto Harsono MD PhDSpA(K)35Conclusion Immunotherapy in asthmatic childrenresults in elevation of IFN-γ and IL-2, diminishIL-4 and IL-5. Addition of inhaled corticosteroid toimmunotherapy results in marked attenuationof IL-5 correlates with greater elevation ofIL-2 and play an important role in themodulation of immune response resulting inthe improvement of FEV-1 reversibility.
  36. 36. Prof Ariyanto Harsono MD PhDSpA(K)36•Reduce development of Rhinitis toasthma•Reduce developing new sensitization•Prevent allergic children from going onto develop asthma•Rhinitis symptom seem to show moresustain relief
  37. 37. Prof Ariyanto Harsono MD PhDSpA(K)37UK 1957-1986: 26 fatal cases 17 forasthma5-35% systemic reactions for asthmaContra indications:•Auto-immune disease•Malignancy•Cardiac disease•Patients receiving beta blocker
  38. 38. Prof Ariyanto Harsono MD PhDSpA(K)381. The primary mechanism of action is ashift in the balance of Th-1 and Th-2cytokine expression in the allergen-challenged site.2. Allergen IT is highly form of treatmentof IgE mediated diseases.3. Highly effective for allergic rhinitis andhypersensitivity to wasp and beevenom.4. Consideration for primary use inasthma is still controversial in regardsthe potential development of adverseevent.
  39. 39. Prof Ariyanto Harsono MD PhDSpA(K)39