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WHAT YOU SHOULD HAVE READ BUT….2012




                 immunotherapy

Attilio Boner
University of
Verona, Italy
sottocutanea
Sottocutanea
Effetti collaterali
Systemic reactions associated with subcutaneous allergen
      immunotherapy: timing and risk assessment
        DaVeiga Ann Allergy Asthma Immunol 2011;106:533

                                Rate of systemic reaction from
                              subcutaneous allergen immunotherapy

                             0.5 –
 A retrospective review
  from January 2001          0.4 –
  to December 2007.
                             0.3 –

 Systemic reaction from
                                          0.28%
                             0.2 –
  immunotherapy.
                             0.1 –

                             1.0
Systemic reactions associated with subcutaneous allergen
      immunotherapy: timing and risk assessment
        DaVeiga Ann Allergy Asthma Immunol 2011;106:533


                             1) All severe reactions occurred
                                within 30 minutes.
                             2) The estimated odds of systemic
 A retrospective review        reaction were almost 6 times
  from January 2001             higher for patients with more
  to December 2007.             than 33% 3 to 4+ positive skin
                                tests (OR = 5.83).
 Systemic reaction from
                             3) For each additional 4+ skin
  immunotherapy.
                                test, the estimated odds for
                                systemic reaction increased
                                by 17% (P = 0.020).
sublingual
Sublingual immunotherapy not effective in house dust
           mite-allergic children in primary care
             De Bot, Pediatr Allergy Immunol 2012;23:150

                                       Mean nose symptom score
 251 children (6–18 yrs)             after 2 years of treatment
  with house dust mite–      03 –
  induced allergic
  rhinitis
                             02 –    2.26        ns
 SLIT with Oralgen                                    2.02
  House Dust Mite
  (Oralgen Mijten, Artu      01 –
  Biologicals, Lelystad, T
  he Netherlands) or
  placebo                     0
                                      SLIT            PLACEBO
 for 2 years
Sublingual immunotherapy not effective in house dust
           mite-allergic children in primary care
             De Bot, Pediatr Allergy Immunol 2012;23:150

                                       Mean nose symptom score
 251 children (6–18 yrs)             after 2 years of treatment
  with house dust mite–      03 –
  inducedSublingual
           allergic
  rhinitis
    immunotherapy with
      house dust mite        02 –    2.26        ns
 SLIT with Oralgen
        allergen was                                   2.02
  House Dust Mite
  (Oralgen better Artu
      not Mijten, than
                             01 –
            placebo
  Biologicals, Lelystad, T
  he Netherlands) or
  placebo                     0
                                      SLIT            PLACEBO
 for 2 years
Epicutaneous allergen administration: is this the future
         of allergen-specific immunotherapy?
                 Senti, Allergy 2011;66:798




 Allergen-specific immunotherapy (SIT) either
   subcutaneously or via the sublingual route
   is effective, but only few patients (<5%) choose
   immunotherapy, as treatment takes several years
   and because allergen administrations are associated
   with local and, in some cases, even systemic allergic
   side-effects.
Epicutaneous allergen administration: is this the future
         of allergen-specific immunotherapy?
                  Senti, Allergy 2011;66:798

  In order to resolve these two major drawbacks, the ideal
   application site of SIT should have two characteristics.

   - 1st it should contain a high number of potent antigen-
    presenting cells to enhance efficacy and shorten treatment
    duration;
   - 2nd it should be nonvascularized in order to minimize
    inadvertent systemic distribution of the allergen;

  The epidermis, a nonvascularized multilayer
   epithelium, that contains high numbers of potent antigen-
   presenting Langerhans cells (LC) could therefore be an
   interesting administration route.
Epicutaneous allergen administration: is this the future
          of allergen-specific immunotherapy?
                          Senti, Allergy 2011;66:798
Timeline for the developments in allergen-specific immunotherapy




On the top: Development of currently approved forms of allergen-specific immunotherapy.
On the bottom: Development of epicutaneous allergen-specific immunotherapy.
Recombinant DNA immunotherapy ameliorate established
    airway allergy in a IL-10 dependent pathway.
               Fonseca, Clin Exp Allergy 2012;42:131


 Background Previous studies have established that mycobacterial
 infections (M. vaccae) ameliorate allergic inflammation.
 However,      a non-infectious approach that controls allergic
 responses might represent a safer and more promising strategy.
 The 60–65 kDa heat shock protein (Hsp) family is endowed
 with anti-inflammatory properties, but it is still unclear whether
 and how single mycobacterial Hsp control allergic disorders.
 Objective Therefore, in this study we determined whether
 the administration of Mycobacterial leprae Hsp65 expressed
 by recombinant a DNA plasmid could attenuate a previously
 established allergic response.
Recombinant DNA immunotherapy ameliorate established
    airway allergy in a IL-10 dependent pathway.
                Fonseca, Clin Exp Allergy 2012;42:131


                 Sensitized and challenged with ovalbumin




                       Administration of Mycobacterial leprae Hsp65
                       expressed by recombinant a DNA plasmid.


Allergic mice
                            (-)
                          Eosinophilia, pulmonary inflammation,
                          Th2 cytokine and mucus production
Recombinant DNA immunotherapy ameliorate established
    airway allergy in a IL-10 dependent pathway.
              Fonseca, Clin Exp Allergy 2012;42:131


                Sensitized and challenged with ovalbumin




                       Administration of Mycobacterial leprae Hsp65
      Inhibition       expressed by recombinant a DNA plasmid.
of allergic response
    is dependent
Allergic IL-10
      on mice
     production.            (-)
                         Eosinophilia, pulmonary inflammation,
                         Th2 cytokine and mucus production
What 2012 immunotherapy

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What 2012 immunotherapy

  • 1. WHAT YOU SHOULD HAVE READ BUT….2012  immunotherapy Attilio Boner University of Verona, Italy
  • 4. Systemic reactions associated with subcutaneous allergen immunotherapy: timing and risk assessment DaVeiga Ann Allergy Asthma Immunol 2011;106:533 Rate of systemic reaction from subcutaneous allergen immunotherapy 0.5 –  A retrospective review from January 2001 0.4 – to December 2007. 0.3 –  Systemic reaction from 0.28% 0.2 – immunotherapy. 0.1 – 1.0
  • 5. Systemic reactions associated with subcutaneous allergen immunotherapy: timing and risk assessment DaVeiga Ann Allergy Asthma Immunol 2011;106:533 1) All severe reactions occurred within 30 minutes. 2) The estimated odds of systemic  A retrospective review reaction were almost 6 times from January 2001 higher for patients with more to December 2007. than 33% 3 to 4+ positive skin tests (OR = 5.83).  Systemic reaction from 3) For each additional 4+ skin immunotherapy. test, the estimated odds for systemic reaction increased by 17% (P = 0.020).
  • 7. Sublingual immunotherapy not effective in house dust mite-allergic children in primary care De Bot, Pediatr Allergy Immunol 2012;23:150 Mean nose symptom score  251 children (6–18 yrs) after 2 years of treatment with house dust mite– 03 – induced allergic rhinitis 02 – 2.26 ns  SLIT with Oralgen 2.02 House Dust Mite (Oralgen Mijten, Artu 01 – Biologicals, Lelystad, T he Netherlands) or placebo 0 SLIT PLACEBO  for 2 years
  • 8. Sublingual immunotherapy not effective in house dust mite-allergic children in primary care De Bot, Pediatr Allergy Immunol 2012;23:150 Mean nose symptom score  251 children (6–18 yrs) after 2 years of treatment with house dust mite– 03 – inducedSublingual allergic rhinitis immunotherapy with house dust mite 02 – 2.26 ns  SLIT with Oralgen allergen was 2.02 House Dust Mite (Oralgen better Artu not Mijten, than 01 – placebo Biologicals, Lelystad, T he Netherlands) or placebo 0 SLIT PLACEBO  for 2 years
  • 9. Epicutaneous allergen administration: is this the future of allergen-specific immunotherapy? Senti, Allergy 2011;66:798 Allergen-specific immunotherapy (SIT) either subcutaneously or via the sublingual route is effective, but only few patients (<5%) choose immunotherapy, as treatment takes several years and because allergen administrations are associated with local and, in some cases, even systemic allergic side-effects.
  • 10. Epicutaneous allergen administration: is this the future of allergen-specific immunotherapy? Senti, Allergy 2011;66:798  In order to resolve these two major drawbacks, the ideal application site of SIT should have two characteristics. - 1st it should contain a high number of potent antigen- presenting cells to enhance efficacy and shorten treatment duration; - 2nd it should be nonvascularized in order to minimize inadvertent systemic distribution of the allergen;  The epidermis, a nonvascularized multilayer epithelium, that contains high numbers of potent antigen- presenting Langerhans cells (LC) could therefore be an interesting administration route.
  • 11. Epicutaneous allergen administration: is this the future of allergen-specific immunotherapy? Senti, Allergy 2011;66:798 Timeline for the developments in allergen-specific immunotherapy On the top: Development of currently approved forms of allergen-specific immunotherapy. On the bottom: Development of epicutaneous allergen-specific immunotherapy.
  • 12. Recombinant DNA immunotherapy ameliorate established airway allergy in a IL-10 dependent pathway. Fonseca, Clin Exp Allergy 2012;42:131 Background Previous studies have established that mycobacterial infections (M. vaccae) ameliorate allergic inflammation. However, a non-infectious approach that controls allergic responses might represent a safer and more promising strategy. The 60–65 kDa heat shock protein (Hsp) family is endowed with anti-inflammatory properties, but it is still unclear whether and how single mycobacterial Hsp control allergic disorders. Objective Therefore, in this study we determined whether the administration of Mycobacterial leprae Hsp65 expressed by recombinant a DNA plasmid could attenuate a previously established allergic response.
  • 13. Recombinant DNA immunotherapy ameliorate established airway allergy in a IL-10 dependent pathway. Fonseca, Clin Exp Allergy 2012;42:131 Sensitized and challenged with ovalbumin Administration of Mycobacterial leprae Hsp65 expressed by recombinant a DNA plasmid. Allergic mice (-) Eosinophilia, pulmonary inflammation, Th2 cytokine and mucus production
  • 14. Recombinant DNA immunotherapy ameliorate established airway allergy in a IL-10 dependent pathway. Fonseca, Clin Exp Allergy 2012;42:131 Sensitized and challenged with ovalbumin Administration of Mycobacterial leprae Hsp65 Inhibition expressed by recombinant a DNA plasmid. of allergic response is dependent Allergic IL-10 on mice production. (-) Eosinophilia, pulmonary inflammation, Th2 cytokine and mucus production