A Mouse Model of Anaphylaxis and Atopic Dermatitis to Salt-Soluble Wheat Protein Extract (1)
Recent estimates show that the combined prevalence of celiac disease, wheat allergy, and non-celiac gluten sensitivities in the USA is surprisingly up to 10%. Wheat is implicated in multiple types of immune-me- diated adverse reactions, as follows: (i) wheat causes typi- cal food allergy (e.g., anaphylaxis, atopic dermatitis, etc.) mediated by IgE antibodies; (ii) it causes non-IgE or cell-mediated reactions (e.g., eosinophilic esophagitis, eosinophilic gastritis); (iii) it also triggers autoimmune diseases associated with autoantibody production and autoreactive T cell responses (celiac disease, dermatitis herpetiformis); (iv) it is linked to neuroimmune reactions (e.g., gluten ataxia), and (v) more recently, it is linked to a new disease known as non-celiac gluten sensitivity.
Groups of mice were injected by the intraperitoneal (IP) route 4 times (days 0, 10, 24, 40) with SSWP extract (0.01 mg/mouse/injection) plus alum (1 mg/mouse). Low levels of SIgE antibody levels were detectable by day 26 after first sensitization, but reached significantly high levels by day 46. A time-dependent increase in TIgE was observed.
Salt-Soluble Wheat Protein (SSWP)-sensitized mice exhibited signif- icant HSR during the next 30 min post challenge.
IP challenge with SSWP elicited a robust elevation of mMCP-1 compared to the levels found in the pre-challenge plasma sample. A significant positive correlation (r = 0.87) between the mMCP-1 concentration and the drop in RT at 10 min post challenge was observed.
The SSWP-sensitized mice (5/8) developed marked dermatitis lesions and alopecia. Histopathology studies demonstrated sig- nificant degranulation of mast cells in the lesions.
Selective and significant elevations of cytokines and chemokines, associated with Th2 and Th17 responses, were noted in the lesions. Proinflammatory/Th1-associated IFN-γ, TNF-α, IL-1β, and CXCL9 (MIG, a CXCR3 ligand) were also elevated.
The analysis of wheat proteins for IgE antibody binding identified 3 protein allergens – 1 major allergen at 65 kDa and 2 minor allergens at 55 and 43 kDa.
Bodinier et al. developed a mouse model using gliadin/alum IP sensitization and intranasal challenge in BALB/c, B10.A/C3H/HeJ mice. They studied IgE antibody responses and eosinophil influx into airways as disease markers and found BALB/c to be the best responder. Denery-Papini et al. developed a BALB/c model using gliadins, and LTP1 plus alum by IP sensitization as in the above study and evaluated IgE responses. Gourbeyre et al. used native and deamidated gliadins plus alum and used IP sensitization and IP challenge methods in BALB/c mice. Abe et al. also used deamidated gliadins plus alum and BALB/c mice, but used IP sensitization followed by intragastric challenges.