Historical overview

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Historical overview

• Pr G. Pauli
• Hôpitaux Universitaires de Strasbourg

Bischenberg 21 septembre 2007
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Allergens and allergic diseases
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(1)

• 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

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(2)

• 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).

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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).Breitenede
  r H et al. - Embo J

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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

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Over the past 15 years the applications of rec
DNA 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).

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Since the 90ies

• Demonstration of biological in vivo activity of
  rec. allergens
• By skin tests
• Moser et al., r Asp f 1 J Immunol 1992
  Aspergillus
• Menz et al., r Bet v 1 Clin Exp Allergy 1996
  Birch
• Pauli et al., r Bet v 1 JACI 1996 Birch r Bet
  v 2
• Heiss 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

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More recently (21st 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.

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For the clinician (1)

• Learning the importance of molecular allergens
  involved in allergic diseases

Example for grass pollens (given by M. Hrabina,
Stallergènes, France)
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For the clinician (2)

• Better identification of cross reactivities
  thanks to the repertory of molecular allergens
• between respiratory allergens,
• between food allergens,
• between respiratory and food allergens.
• New approaches towards allergy vaccinations.