Author
PONS, LAURENT - DUKE UNIVERSITY | |
PONNAPPAN, USHA - DUKE UNIVERSITY | |
HALL, RENEE - AR CHILDREN'S HOSPITAL | |
SIMPSON, PIPPA - AR CHILDREN'S HOSPITAL | |
COCKRELL, GAEL - UAMS/AR CHILDREN'S HOSPIT | |
WEST, MICHAEL - UAMS/ACNC | |
SAMPSON, HUGH - MOUNT SINAI SCH OF MED | |
HELM, RICKI - UAMS/ACNC | |
BURKS, WESLEY - DUKE UNIVERSITY |
Submitted to: Journal of Allergy Clinical Immunology
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 6/24/2005 Publication Date: 10/15/2004 Citation: Pons, L., Ponnappan, U., Hall, R.A., Simpson, P., Cockrell, G., West, M.C., Sampson, H.A., Helm, R.M., Burks, W.A. 2004. Soy immunotherapy for peanut-allergic mice: modulation of the peanut-allergic response. Journal of Allergy and Clinical Immunology. 114(4):915-921. Interpretive Summary: America households with individuals suffering from food allergy alter their dietary habits because of either a perceived or known food allergy. The only proven therapy is complete avoidance of the food causing the clinical symptoms. For example, individuals suffering gastrointestinal allergy to peanuts try to avoid all food products containing peanuts in any form, i.e., peanuts, peanut meal, or peanut butter. However, it is often difficult to identify some products that contain peanuts because the product is not labeled correctly and accidental ingestion of peanuts can take place resulting in a life-threatening allergic response. Preliminary studies are being undertaken in animal models to determine if there is a mechanism for desensitization to peanuts to the level that very small amounts of “hidden” peanut sources can be ingested without causing a life-threatening response. Many peanut-sensitive individuals can eat other members of the legume family of foods such as soybeans without having allergic symptoms. Although the mechanism is unknown, our studies suggest that peanut sensitive animals treated with soybean had a significant reduction of clinical symptoms after peanut challenges compared to placebo-controlled animals. It remains to be determined if increasing the consumption of soybean in patients allergic to peanuts can be used as a treatment option. Technical Abstract: Background Allergen-specific immunotherapy (IT) is an effective therapeutic modality to prevent further anaphylactic episodes in patients with insect sting hypersensitivity and is being investigated for peanut allergy. So far, peanut-specific IT has been unsuccessful because of the side effects of therapy. Soybean seed storage proteins share significant homology with the respective peanut allergens. Objective This study was undertaken in mice to investigate whether specific doses of soybean would desensitize peanut-allergic mice. Methods C3H/HeJ mice were sensitized to peanut with 3 intraperitoneal (IP) injections of crude peanut extract. The mice were desensitized by IP injections with either crude peanut or soybean extract for 4 weeks, 3 times a week. Controls included placebo desensitization with PBS and naive mice. After 2 weeks of rest, mice were challenged IP with crude peanut extract. Thirty minutes later, symptom scores and body temperatures were recorded. Serum immunoglobulins, peanut-induced splenocyte proliferation, and secreted cytokines were measured before and after desensitization. Results The clinical symptoms in the soybean- and peanut-desensitized animals were markedly reduced compared with the placebo-treated mice. Specific IgG1 levels to crude peanut were significantly lower in the soy IT group than in the peanut IT group. The cellular response to crude peanut was also downregulated in the soy IT group, as shown by decreased peanut-specific stimulation indices and a cytokine profile skewed toward a TH1 response. Conclusions Soy IT can be used to desensitize/downregulate peanut-specific response in peanut-allergic mice and could provide a new therapeutic intervention for peanut allergy. |