Oral sensitization to peanut is highly enhanced by application of peanut extracts to intact skin, but is prevented when CpG and cholera toxin are added.
BACKGROUND
CpG oligonucleotides might offer an alternative to conventional immunotherapy in preventing and potentially reversing Th2-biased immune deregulation which leads to allergy. However, non-invasive ways of administration, especially in peanut-allergic patients, should be explored.


METHODS
One hundred micrograms of whole peanut protein extract (PE) alone, or mixed with cholera toxin (CT, 50 microg) plus CpG (100 microg) as adjuvant, was applied on intact skin of mice (40 min, twice). Initiation of an immune response was monitored by detection of specific antibodies in sera. The effect of this pretreatment on a further oral sensitization by PE was then evaluated by assaying antibodies and cytokines specific for PE and purified allergens. Cytokine production in liver 40 min after skin application was also assayed.


RESULTS
Two brief skin applications of PE alone highly potentiated further oral sensitization, as demonstrated by very intense specific IgE, IL-4 and IL-5 productions. Conversely, skin pretreatment with PE and CT + CpG efficiently prevented further sensitization via gastro-intestinal exposure. In both cases, the specificity of the antibodies and cytokines was the same as in control mice. CT + CpG treatment allowed the rapid production of IL-12 and TGFbeta in liver and of specific IgG2a in sera, suggesting the activation of Th1 and/or regulatory T cells.


CONCLUSIONS
Oral sensitization to peanut is highly enhanced by a previous short exposure of allergens to intact skin. Conversely, the use of CT + CpG adjuvant for skin application efficiently prevents further oral sensitization. The potential of such treatment in specific immunotherapy needs to be evaluated.
Adel-Patient
Karine
K
Laboratoire Inra d'Immuno-Allergie Alimentaire, CEA de Saclay, Gif-sur-Yvette, France. karine.patient@cea.fr
Ah-Leung
Sandrine
S
Bernard
Hervé
H
Durieux-Alexandrenne
Coralie
C
Créminon
Christophe
C
Wal
Jean-Michel
JM
D000284:Administration, Oral; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology*; D005260:Female; D007070:Immunoglobulin A / Q000032:analysis; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008099:Liver / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D021183:Peanut Hypersensitivity / Q000209:etiology / Q000628:therapy*; D010936:Plant Extracts / Q000276:immunology; D012867:Skin / Q000276:immunology*
C408982:CPG-oligonucleotide; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D015848:Interleukin-5; D009838:Oligodeoxyribonucleotides; D010936:Plant Extracts; D015847:Interleukin-4; D007073:Immunoglobulin E; D002772:Cholera Toxin