MRGPRX2 in general anaesthetic reactions

General anaesthesia is a very important component of modern surgery, and is necessary for many procedures ranging from kidney transplantation to total hip replacement. Anaesthesia requires the careful delivery of anaesthetic drugs, with constant monitoring of the patient by specialized doctors. To facilitate effective anaesthesia neuromuscular blocking agents (NMBAs) such as rocuronium are often used. These drugs relax muscle, enabling surgery to be performed without patient movement. In the vast majority of individuals these drugs are effective and safe, but in rare cases they can produce a severe life-threatening reaction. This severe allergy-like reaction can make the circulation fail, and during surgery can have potentially fatal consequences. This severe drug reaction has similar features to the allergic response termed anaphylaxis. Anaphylaxis can be seen with food allergies, for example in peanut-sensitive individuals, in whom exposure to peanuts can be life-threatening. The similarity of this response seen with neuromuscular blocking drugs suggests a shared common mechanism. In anaphylactic reactions, the body generates an allergic antibody (called IgE) that interacts with the substance to which the patient is allergic to stimulate special immune cells called mast cells and basophils. These cells then release numerous chemicals, such as histamine, that produce the severe symptoms of anaphylaxis. Whilst this IgE mechanism is important to some drug allergy, there are also cases where no specific IgE can be found to explain the reaction. Recently, a new mechanism has been revealed whereby certain drugs, such as rocuronium, can directly stimulate a receptor protein on the surface of mast cells leading to their activation. Despite this advance, key questions remain - why are only some people affected? Secondly, by understanding this new mechanism - can we identify individuals who are likely to suffer these reactions, sparing them from potentially devastating consequences? This project aims to answer these questions and in so doing provide a more individualised and safer approach to the use of muscle relaxant drugs during surgery.