111:
In Vivo Mast Cell Activation by the MRGPRX2 Receptor Ligands
Saturday, March 3, 2018
South Hall A2 (Convention Center)
Maria Shtessel, MD, Eric T. Oliver, MD, Kristin L. Chichester, MS, Sarbjit Singh Saini, MD FAAAAI
RATIONALE: The MRGPRX2 receptor activates mast cells in a non-IgE mediated manner, and is upregulated in expression in patients with chronic spontaneous urticaria (CSU). While in vitro studies show MRGPRX2 activation by substance P, VIP, compound 48/80 and therapeutic drugs associated with pseudoallergic reactions, no human studies of MRGPRX2 activation have been performed. We examined skin mast cell responses to MRGPRX2 activation using 2 known MRGPRX2 ligands (icatibant and atracurium) in healthy and CSU subjects. We also examined skin response to histamine titration in healthy and CSU subjects.

METHODS: Healthy controls (n=9) and urticaria subjects (n=2) underwent serial intradermal skin titration testing with icatibant and atracurium (1 x 10-6 to 1 x 10-1 mg/ml) insulin and saline as negative controls, and histamine serial titration. Wheal size was calculated after 15 minutes. The mean concentration of each ligand that yielded a 5 mm wheal (ED5) or AUC was determined.

RESULTS: The ED5 for healthy and urticaria subjects for histamine was 2.8 x 10-3 mg/ml and 2.1 x 10-4 mg/ml and 6.9 x 10-1 mg/ml and 2.8 x 10-3 mg/ml for icatibant respectively. For atracurium, the mean wheal diameter for the healthy subjects did not reach 5 mm, and therefore, the area under the curve was calculated, 7.03 for healthy and 19.56 for urticaria subjects.

CONCLUSIONS: The ED5 for icatibant suggests that there is a heightened sensitivity to MRGX2 ligands in CSU subjects in support of heightened protein expression noted in past studies.