Anaphylaxis Preparedness Initiative for Allergen Immunotherapy – Implementation of a Policy for Carrying Autoinjectable Epinephrine

Abstract

RATIONALE: Antibody Fab fragments (Fabs) prepared by digestion with papain lack effector functions including mast cell degranulation due to the absence of the Fc portion. In the present study, we tested the hypothesis that the application of allergen-specific monoclonal antibody (mAb) IgG1 Fabs downregulated atopic dermatitis-like skin inflammation in mice. METHODS: Balb/c mice sensitized by intraperitoneal injections of antiovalbumin (OVA) IgE mAbs on days 0, 1, 2, 7, 8, and 9 were challenged with OVA by its application to the skin on days 1, 2, 3, 8, 9, and 10. Anti-OVA IgG1 mAb (O1-10) Fabs were applied to the skin 30 min before the fourth to sixth challenges followed by measurement of clinical symptoms including erythema/hemorrhage, edema, scarring/dryness, and excoriation/erosion of the skin. Histological changes in the skin were also investigated. RESULTS: Significantly increased clinical symptoms were observed during the third to sixth OVA challenges. The application of O1-10 Fabs to the skin resulted in marked suppression of all of the clinical symptoms. Intact O1-10 failed to affect the clinical symptoms. Histologically, epidermal thickness and neutrophil accumulation in the skin were decreased following the treatment with O1-10 Fabs. Furthermore, the suppression of the clinical symptoms by the O1-10 Fabs was associated with decreases in mast cells as well as IL-17A and IL-13 in the skin. CONCLUSIONS: The present study demonstrates for the first time that the application of pathogenic allergen-specific IgG1 mAb Fabs to the skin appears to be effective in downregulating IgE-mediated atopic dermatitislike skin inflammation.