Researchers from Johns Hopkins and University of Alberta have identified a single protein receptor, MRGPRX2, as the root of painful and dangerous allergic reactions to medications and other substances. Finding a new drug that targets the problematic protein could help smoothen treatment for patients with prostate cancer, diabetes and even HIV.
Previous studies have linked reactions (such as pain, itching and rashes at the injection sites of many drugs) to part of the immune system known as mast cells. When specialized receptors on the outside of mast cells detect antibodies, they get into action, releasing histamine and other substances that spark inflammation and draw other immune cells into the area. The antibodies are produced by other immune cells in response to bacteria, viruses or other perceived threats. However, the researchers noticed that sometimes no antibodies are produced even though many of these injection site reactions look like an allergic response.
To understand the cause of the reactions, researchers first conducted mice studies to find out which mast cell receptor, or receptors, responded to the drugs. They found that all drugs turn out to trigger a single receptor, known as MRGPRX2.
To find out whether eliminating the receptor would eliminate the allergic reactions, the research team disabled the gene for the suspect receptor in mice. They found that these 'knockout' mice did not have any of the drug allergy symptoms that their genetically normal counterparts displayed. The researchers are now working to find compounds that could safely block the culprit receptor MRGPRX2. This drug would not prevent true allergic reactions, but would block only the pseudoallergic reactions triggered by MRGPRX2, which could improve the lives of many patients.
Their study is published in the journal 'Nature'.