Evaluation of MRGPRX2 receptor mutations in patients with vancomycin-induced red neck syndrome

Vancomycin is a tricyclic glycopeptide antibiotic isolated from Amycolatopsis orientalis that is effective against gram-positive bacteria, especially MRSA (Methicillin-Resistant Staphylococcus aureus). It inhibits RNA synthesis and the polymerization of peptidoglycan, an essential component of the bacterial cell wall. Vancomycin can cause two types of hypersensitivity reactions: one is IgE-mediated anaphylaxis, and the other is red neck syndrome, an IgE-independent mast cell degranulation. Both reactions involve mast cell activation. Red neck syndrome is an infusion-related reaction peculiar to vancomycin. It is an idiopathic infusion reaction in which specific antibodies are not involved; and unlike allergic reactions, can occur with the first exposure to vancomycin. Symptoms are typically an erythematous rash, fever, paresthesia, itching involving the face, neck, and upper body, agitation and hyperthermia around the mouth. Red neck syndrome occurs mainly with parenteral administration of vancomycin and its adverse effects may begin approximately 4-10 minutes after the start of the infusion or soon after the infusion ends. Hypersensitivity reactions caused by vancomycin are due to the effect of vancomycin on mast cells. Red neck syndrome causes histamine degranulation from mast cells and basophils independent of IgE or complement. It was reported before that vancomycin activates mast cells via a non-IgE mediated pathway in mice. It was shown that vancomycin can directly induce mast cell degranulation via the MAS-related G-protein-coupled receptor X2 (MRGPRX2). The aim of the thesis is to determine genetic variations in the protein-coding region of the MRGPRX2 gene in patients with clinical features of hypersensitivity reactions related to vancomycin. To gain knowledge about the different variants of the MRGPRX2 receptor can be helpful in assessing the propensity of patients for experiencing adverse reactions in response to certain drugs.