IgE Neutralization Reverses Trimellitic Anhydride-Induced Urticaria in Humanized CD34+ Mice

Urticaria is a significant challenge affecting the quality of life for a substantial population worldwide, manifested by the sudden appearance of wheals, erythema, and pruritus triggered by allergic reactions, infections, or physical stimuli. Immunoglobulin E (IgE) plays a pivotal role in urticaria pathogenesis by mediating mast cell accumulation and degranulation to regulate the release of inflammatory mediators such as histamine.

We developed a humanized CD34+ mouse model of urticaria by sensitizing the depilated skin topically with Trimellitic anhydride (TMA) on four occasions, with anti-human IgE as the positive control. Four consecutive days after the final sensitization, we observed and scored animal ear conditions, and enumerated scratching frequency. Additionally, mast cell counts in the skin and ear were evaluated.

TMA-sensitized animals exhibited increased ear thickness, scoring, scratching frequency, and mast cell numbers in both skin and ear compared to normal animals. Toluidine blue staining confirmed a significant rise in mast cell numbers in TMA-sensitized mice, correlating with elevated histamine levels.

Treatment with anti-human IgE ameliorated urticaria symptoms, showcasing comparable ear thickness, mast cell numbers in the ear and skin, and scratching frequencies to the normal animals. Our findings indicate that IgE neutralization effectively reversed TMA-induced urticaria in humanized CD34+ mice.