allergen immunotherapy for allergic diseases

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  • 1. Prof Ariyanto Harsono MD PhDSpA(K)1Prof Ariyanto Harsono MD, PhD, SpA(K)

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. Prof Ariyanto Harsono MD PhDSpA(K)3Tree polen 4. Prof Ariyanto Harsono MD PhDSpA(K)4 5. Prof Ariyanto Harsono MD PhDSpA(K)5 6. Prof Ariyanto Harsono MD PhDSpA(K)6Bee sting 7. Prof Ariyanto Harsono MD PhDSpA(K)7Dermatophagoides pterisynus 8. Prof Ariyanto Harsono MD PhDSpA(K)8Dermatophagoides farinai 9. Prof Ariyanto Harsono MD PhDSpA(K)9The main allergen is the feces of mite 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. Prof Ariyanto Harsono MD PhDSpA(K)11Atopy 12. Prof Ariyanto Harsono MD PhDSpA(K)12allergen2004: 3:234-237Allergy AllergyGrow outAllergenExposureAllergen IT 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. 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. Prof Ariyanto Harsono MD PhDSpA(K)152004: 3:234-237Allergen exposureAllergen IT 16. Prof Ariyanto Harsono MD PhDSpA(K)16Pre Immunotherapy Post ImmunotherapyJ Allergy Clin Immunol 2004 Volume 113 Number 6 :1234-1237 17. Prof Ariyanto Harsono MD PhDSpA(K)17Prof Ariyanto Harsono MD PhDSpA(K) 18. Prof Ariyanto Harsono MD PhDSpA(K)18Allergen exposureIL-4, IL-5IL-13Th-2 CellIL-13B Cell 19. Prof Ariyanto Harsono MD PhDSpA(K)19IgGAllergen ITTh-1 CellIL-12 IFN-IL-2B Cell 20. Prof Ariyanto Harsono MD PhDSpA(K)20Pre Immunotherapy Post ImmunotherapyJ Allergy Clin Immunol 2004 Volume 113 Number 6 :1234-1237 21. Prof Ariyanto Harsono MD PhDSpA(K)21:Pre ImmunotherapyPost ImmunotherapyJ Allergy Clin Immunol 2004 Volume 113 Number 6 :1234-1237IFN-Prof Ariyanto Harsono MD PhDSpA(K) 22. Prof Ariyanto Harsono MD PhDSpA(K)22Pre ImmunotherapyPost ImmunotherapyJ Allergy Clin Immunol 2004 Volume 113 Number 6 :1234-1237 23. 23Other studyDurham 1998, reportedreduce of IL-4 and IL-5;increase of IFN- 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. Prof Ariyanto Harsono MD PhDSpA(K)242004: 3:234-237 25. Prof Ariyanto Harsono MD PhDSpA(K)252004: 3:234-237Prof Ariyanto Harsono MD PhDSpA(K) 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. Prof Ariyanto Harsono MD PhDSpA(K)27(Akdis, J Clin Invest 1998;102:98-106)Prof Ariyanto Harsono MD PhDSpA(K) 28. Prof Ariyanto Harsono MD PhDSpA(K)28Allergen extract:-Whole body extract-Pure venom extract10% residual risk 29. Prof Ariyanto Harsono MD PhDSpA(K)29Effective in Seasonal allergic rhinitisLess effective in perennial allergic rhinitisMark improvement in tolerance of catexposure 30. Prof Ariyanto Harsono MD PhDSpA(K)30Common indication in North America andEuropeMeta analysis 1954-1998: beneficial effectDBPC: 60-75% reduce of symptom score inpatients with grass pollen allergyEconomic analysis: less cost than pharmaco-therapy 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. 32IL-12IL-5IL-4IL-13Immunotherapy>IgE IgGAsthma symptom(Rev FEV-1)Asthma symptom(Rev FEV-1)CortikosteroidIFN- IL-2>//Group AGroup BGroup CStudy from Surabaya(Harsono, Dissertation 2004)Prof Ariyanto Harsono MD PhDSpA(K) 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. 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- 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. Prof Ariyanto Harsono MD PhDSpA(K)35Conclusion Immunotherapy in asthmatic childrenresults in elevation of IFN- 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. Prof Ariyanto Harsono MD PhDSpA(K)36Reduce development of Rhinitis toasthmaReduce developing new sensitizationPrevent allergic children from going onto develop asthmaRhinitis symptom seem to show moresustain relief 37. Prof Ariyanto Harsono MD PhDSpA(K)37UK 1957-1986: 26 fatal cases 17 forasthma5-35% systemic reactions for asthmaContra indications:Auto-immune diseaseMalignancyCardiac diseasePatients receiving beta blocker 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. Prof Ariyanto Harsono MD PhDSpA(K)39

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