Historical overview Pr G. Pauli Hôpitaux Universitaires de Strasbourg Bischenberg 21 septembre...
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Transcript of Historical overview Pr G. Pauli Hôpitaux Universitaires de Strasbourg Bischenberg 21 septembre...
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.