The 2S albumin allergens of Arachis hypogaea, Ara h 2 and Ara h 6, are the major elicitors of anaphylaxis and can effectively desensitize peanut-allergic mice

Clin Exp Allergy. 2012 Feb;42(2):326-36. doi: 10.1111/j.1365-2222.2011.03934.x.

Abstract

Background: Ara h 2 and Ara h 6, co-purified together in a 13-25 kD fraction (Ara h 2/6; 20 kD fraction) on gel filtration chromatography, account for the majority of effector activity in a crude peanut extract (CPE) when assayed with RBL SX-38 cells sensitized with IgE from human peanut allergic sera.

Objectives: To determine if Ara h 2/6 are the primary peanut allergens responsible for allergic reactions in vivo and to determine if Ara h 2/6 would be sufficient to prevent allergic reactions to a complete CPE.

Methods: An oral sensitization mouse model of peanut allergy was used to assess the activity of Ara h 2/6 (20 kD) and CPE without the 20 kD fraction (CPE w/o 20 kD) for allergic provocation challenge and immunotherapy. The activity of these preparations was also tested in an assay of histamine release from human basophils in whole blood.

Results: Compared with mice challenged with control CPE, mice challenged with CPE w/o 20 kD experienced reduced symptoms (P < 0.05) and a smaller decrease in body temperature (P < 0.01). Results with the basophil histamine release assay corroborated these findings (P < 0.01). The mouse model was also used to administer Ara h 2/6 (20 kD) in an immunotherapy protocol, in which peanut-allergic mice treated with the 20 kD fraction experienced significantly reduced symptoms, changes in body temperature, and mast cell protease (MMCP-1) release compared with placebo (P < 0.01 for all parameters). Importantly, immunotherapy with the 20 kD fraction was just as effective as treatment with CPE, whereas CPE w/o 20 kD was significantly less effective for higher dose peanut challenges.

Conclusions and clinical relevance: Ara h 2/6 are the most potent peanut allergens in vivo and can be used to desensitize peanut-allergic mice. These results have potential implications for clinical research in the areas of diagnosis and immunotherapy for peanut allergy.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • 2S Albumins, Plant* / immunology
  • 2S Albumins, Plant* / pharmacology
  • Anaphylaxis / immunology
  • Anaphylaxis / therapy*
  • Animals
  • Antigens, Plant* / immunology
  • Antigens, Plant* / pharmacology
  • Arachis / adverse effects*
  • Arachis / immunology
  • Basophils / immunology
  • Desensitization, Immunologic*
  • Disease Models, Animal
  • Female
  • Glycoproteins* / immunology
  • Glycoproteins* / pharmacology
  • Histamine / immunology
  • Humans
  • Male
  • Mice
  • Peanut Hypersensitivity / immunology
  • Peanut Hypersensitivity / therapy*
  • Tryptases / immunology

Substances

  • 2S Albumins, Plant
  • Antigens, Plant
  • Ara h 6 allergen, Arachis hypogaea
  • Ara h II protein, Arachis hypogaea
  • Glycoproteins
  • Histamine
  • Tryptases