1. Molecular allergology and immunotherapy

2. Disclosure
In relation to this presentation, I declare the following, real or perceived conflicts of interest:
Rudolf Valenta has received research grants from
- BIOMAY AG, Vienna, Austria
- Thermofisher, Uppsala, Sweden
and serves as a consultant for both companies.
A conflict of interest is any situation in which a speaker or immediate family members have interests, and those may cause a conflict with the current presentation. Conflicts of interest do not preclude the delivery of the talk, but should be explicitly declared. These may include financial interests (eg. owning stocks of a related company, having received honoraria, consultancy fees), research interests (research support by grants or otherwise), organisational interests and gifts.

3. ALLERGENS: Allergic sensitization, secondary immune response and pathomechanisms
Valenta R. Nat Rev Immunol. 2002, 2:446-53

4. The revolution in the characterization of protein allergens through expression cDNA cloning

5. From allergen genes to new forms of diagnosis and treatment of allergy
Valenta R, et al., Annu.Rev.Immunol, 2010, 28:211-41

6. From allergen genes to new forms of diagnosis and treatment of allergy

7. First demonstration that recombinant allergens can be used for in vitro diagnosis of allergy

8. First demonstration that recombinant allergens can be used for serological diagnosis of allergy
Valenta et al., J. Allergy Clin. Immunol., 1991, 88:889-94

9. First demonstration that recombinant allergens can be used for in vitro diagnosis of allergy

10. First demonstration that recombinant allergens can be used for diagnosis of allergy in basophil activation assays
Valenta et al., J. Allergy Clin. Immunol., 1993, 91: 88-97

11. First demonstration that recombinant allergens can be used for diagnosis of allergy in basophil activation assays
Valenta et al., J. Allergy Clin. Immunol., 1993, 91: 88-97

12. Recombinant allergens for in vivo allergy diagnosis by skin prick testing
Pauli et al., J.Allergy Clin. Immunol., 1996, 97:1100-9

13. Development of the concept of component-resolved allergy diagnosis

14. Allergen microarrays open the door for testing for multiple allergens with minute amounts of serum
FASEB J. 2002

15. Improved diagnosis with recombinant allergen-based diagnostic tests
More accurate diagnosis of the disease-causing allergen sources with recombinant allergen-based tests facilitates prescription of SIT
Monitoring of the effects of SIT by measurement of allergen-specific IgG development
Hiller R, et al., FASEB J. 2002;16:414-6

16. Skin testing versus chip testing

18. The allergy march in childhood Allergic rhinoconjunctivitis
Food allergies
Genetic factors
Atopic dermatitis can be the first sign of a lifelong susceptibility for allergic diseases
Allergic rhinoconjunctivitis
Bronchial asthma 40% of infants having atopic dermatitis develop asthma until the age of 4

19. European-wide assessment of the molecular evolution of allergic sensitization in birth cohorts: MeDALL

20. The MeDALL allergen chip

21. List of allergens contained on the MeDALLallergen-chip
Lupinek C et al, Methods 2014, 43:

22. Higher sensitivity of the MeDALL-chip to detect allergic sensitization compared to skin testing and CAP testing

24. Prevalences of IgE reactivity to PR-10 proteins
at ages 4, 8 and 16
Westman et al; J Allergy Clin Immunol. 2015, 135,

25. Numbers of children with IgE, upper or lower respiratory symptoms
Westman et al; J Allergy Clin Immunol, in press

26. Probabilities for incident or persistent birch pollen-induced rhinitis in relation to
Bet v 1-specific IgE
Westman et al; J Allergy Clin Immunol, in press

27. The allergen microarray in pediatric allergology
The allergen microarray is the perfect tool to diagnose IgE sensitizations and allergy in childhood
Results from MeDALL indicate that it allows to predict the development of allergic disease according to sensitization profiles
The microarray could be used for obligatory allergy screening in school children

28. „Species-specific“ marker allergens
Genuine sensitization against a certain allergen source
Prediction of symptoms
Cross-reactive marker allergens
Cross-sensitization

29. Component-resolved diagnosis of food allergy

30. Use of microarrayed allergens/antigens in the diagnosis of respiratory diseases

31. Clinical asthma phenotypes and associated pathophysiological mechanisms
Kim et al., Nature Immunol. 2010

32. odds ratio: Der p 5: 4.21 Der p 2: 2.79 Der p 7: 2.54
J Allergy Clin Immunol 2015, in press
odds ratio:
Der p 5: 4.21
Der p 2: 2.79
Der p 7: 2.54

33. Allergen contact via the respiratoriy but not the dermal route increases allergen-specific IgE levels
Niederberger V, et al., Int Arch Allergy Immunol. 2006, 142:

34. Summary:
Microarrays containing respiratory allergens and epitopes from respiratory viruses allow to measure increases of allergen-specific IgE and virus-specific IgG increases
Increases of allergen-specific IgE and virus-specific IgG will allow identifying causes of respiratory disease exacerbations (allergen exposure versus viral infection)

35. The microarray for identifying patients who are suitable for IgE-targeted therapy strategies
recombinant humanized ab to IgE
IgG1-ab, murine CDR < 5 %
binds to Cε3 region of IgE
forms trimeric complexes
blocks binding to FcεRI
In clinical trials (2012):
adults (>12 yrs): 5308
children (6-12 yrs): 914
Outside trials (2012):
> patient treatment years
CDR: complementarity determining region
FcεRI: high affinity receptor
Trimeric complexed do not activate complement system
Holgate ST, QJM 1998

36. Allergen molecule-based tests for accurate prescription of immunotherapy

38. Decision trees for prescription of SIT
Valenta et al,

39. Molecular diagnosis changes the prescription of SIT

40. Monitoring of IT with recombinant allergens
Monitoring of the immunological efficacy of IT
Measurement of specific IgG
Major allergens: Phl p 1, Phl p 5 Bet v 1, Ole e 1
Par j 2

41. Allergen-specific IgG antibodies induced by SIT cause a reduction of allergen-specific IgE binding on ISAC
Wollmann et al., J. Allergy Clin. Immunol. In press

42. The ISAC platform may be compared with the iPhone:
Continuous evolvement of new opportunities!

43. Synthetic allergy vaccines in clinical trials
Valenta R et al., Ann Rev Immunol. 2010: 28:211-41

44. Acknowledgements MeDALL Coordinators
Jean Bousquet
Josep M. Antó
Delphine Smagghe
Partners from MeDALL birth-cohorts
BAMSE (Karolinska Institute, Stockholm, Sweden):
Magnus Wickman
Marianne van Hage
Inger Kull
Niklas Andersson
ECA (Oslo, Norway)
PIAMA (Netherlands)
ROBBIC (Rome and Bologna, Italy)
EGEA (France)
BiB (Bradford, England)
INMA (Catalonia, Spain)
Dept. of Pathophysiology and Allergy Research, Medical University of Vienna
Christian Lupinek
Eva Wollmann
Renata Kiss
Sandra Pahr
Alexandra Baar
Yvonne Resch
Phadia Multiplexing/Thermo Fisher Scientific, Uppsala, Sweden
Thomas Schlederer
Daniel Ebner
Christian Harwanegg

45. PreDicta: www.predicta.eu
Rudolf Valenta
Marianne van Hage
Clarissa
Cabauatan
Katarzyna Niespodziana
Daniela Gallerano
Gunilla Hedlin

46. Acknowledgements www.predicta.eu Karl-Franzens-University of Graz:
Walter Keller
PreDicta members:
Nikolaos G. Papadopoulos
(National Kapodistrian University of Athens, Greece)
Sebastian L. Johnston
(Imperial College London, UK)
David Jackson

47. Thank you for your attention! Rudolf Valenta