Historical overviewHistorical overview

Pr G. Pauli

Hôpitaux Universitaires de Strasbourg

Bischenberg21 septembre 2007

Allergens and allergic diseasesAllergens and allergic diseases

In the 70ies

Allergenic sources were studied using electrophoretical methods (IEF, SDS-Page gel, crossed immunoelectrophoresis).

In the early 80ies

IgE responses against different components were determined (immunoblotting)

Peltre G, Lapeyre J, David B. A nitrocellulose immunoprint technique to detect human antibodies to allergen extracts. JACI 1982

(1)

Since the 90ies

Purification of allergenic proteins, determination of

peptide sequences, use of monoclonal antibody

technology (by immunization of mice with purified

allergens).

Use of DNA technology for characterization and

production of recombinant allergens (now the choice

method).

(2)

Some important dates (1)Some important dates (1)

1988 : cDNA cloning of Der p 1 (Dermatophagoïdes

pteronyssinus).

Chua et al. - J Exp Med

1988 : cDNA cloning of white-face hornet venom allergen.

Fang et al. - PNSA

1989 : cDNA cloning of Bet v 1 (Birch).

Breiteneder H et al. - Embo J

Some important dates (2)Some important dates (2) 1991 : cDNA cloning of profilin (a plant panallergen)

Valenta R et al. - Science

1993 : cDNA cloning of Phl p 5 (grass : Phleum pratense).Vrtala S et al. - J of Immunology

1993 : cDNA cloning of Sin a 1 (yellow mustard).First food allergen to be cloned.Gonzales de la Pena, Villalba M et al. - Biochem Biophys Res Commun

Over the past 15 years the applications of rec Over the past 15 years the applications of rec DNA technology to allergens have explodedDNA technology to allergens have exploded

Characterization of 569 allergenic molecules listed in

Allergome (data bank of www.allergens.org) updated

July 2007.

Numerous basic research studies (T cell epitope

mapping, identification of three dimensional

structures, IgE epitope mapping), production of

allergen derivatives with reduced IgE binding capacity

(hypoallergens).

Since the 90Since the 90iesies

Demonstration of biological in vivo activity of rec. allergens By skin tests

Moser et al., r Asp f 1 J Immunol 1992 AspergillusMenz et al., r Bet v 1 Clin Exp Allergy 1996 BirchPauli et al., r Bet v 1 JACI 1996 Birch

r Bet v 2Heiss et al., r Phl p 1,2,5 J Investig Dermatol 1999 Grass

Prick-tests (1 - 100 µg/ml). By provocation tests

Bronchial : Godnic - Cvar et al, rBet v 1, JACI 1997

Nasal : Ruoppi et al., Bos d 2, Clin Exp Allergy 2001 Van Hage Hamsten et al., Bet v 1, Clin Exp Allergy 2002

Conjunctival : Arquint et al., rBet v 1, JACI 1999

More recently (21More recently (21stst Cy) Cy)

Immunotherapy with recombinant allergens

and recombinant hypoallergenic derivatives

demonstration of de novo IgG antibody

responses against rec. allergens,

clinical results of phase 2 are available for 3

studies.

For the clinician (1)For the clinician (1) Learning the importance of molecular allergens

involved in allergic diseases

Example for grass pollens (given by M. Hrabina, Stallergènes, France)

Groupe

1

Groupe

5

Groupe

7

Groupe

2/3

Groupe

10

Groupe 4

Groupe

12

Groupe

11

50%

40%

Groupe13

Low potential

High potential

% of specific IgE to individual molecular allergens

Prevalence ofsensitization

For the clinician (2)For the clinician (2)

Better identification of cross reactivities thanks to the repertory of molecular allergensbetween respiratory allergens,between food allergens,between respiratory and food allergens.

New approaches towards allergy vaccinations.