Researchers Identify Protein Active During Anaphylaxis as Target for Drug Therapy

Researchers Identify Protein Active During Anaphylaxis as Target for Drug Therapy

Parents of food-allergic children know the fears associated with food allergies all too well. Questions like, “Will other parents at a play date remember how to care for my child during a severe allergic reaction?” or “Is the substitute teacher equipped to help my child in the event of a life-threatening allergic event?” may flood parents’ minds on a regular basis. Many parents of kids with food allergies feel on edge all of the time as they worry about the safety of their child.

The fearful state many parents live in is rooted in the knowledge that reactions to food allergens can take a sudden turn for the worse, and urgent and proper attention is required to help their child out of a reactive state. Food allergy reactions are more than just an itch or stomach ache. Food allergies can lead to symptoms from a stuffy nose or itchiness to difficulty breathing, vomiting and even a loss of consciousness. Severe allergic reactions may involve several parts of the body, leading to a life-threatening condition known as anaphylaxis.

New research may be one of the first stepping stones on the path to inhibiting the most dangerous allergic symptoms. New therapies may be on the horizon that could transform the lives of the estimated 5.9 million American children who have food allergies, as well as the lives of their parents.

According to Dr. Simon Hogan, principal investigator of a team of researchers at the Cincinnati Children’s Hospital Medical Center, studies show that more than just immune cells play a role in food allergies. Hogan states, “It is becoming increasingly clear that non-immune cells can also influence anaphylaxis.” Hogan and his team of researchers unveiled several proteins that work together in blood vessels, strengthening the symptoms of respiratory and circulatory responses during allergic response that leads to anaphylaxis.

An allergic reaction takes place when the immune system identifies a protein that is normally considered to be harmless (also known as the allergen) as a threatening invader, initiating a chain of events that lead to symptoms of disease. The interior of these blood vessels are lined with the vascular epithelium (VE), which houses cells that work to form a barrier that prevents fluid from leaking out. When a severe allergic reaction (or anaphylaxis) takes place, this VE barrier is disrupted, allowing fluid to leak from within the blood vessels into surrounding tissues. When this happens, shock, respiratory failure or death may occur.

When an allergic reaction takes place, white blood cells release histamine molecules, which help fight infection and promote healing. Additionally, a protein called interleukin 4 (IL-4) is also released by white blood cells during an allergic reaction. Researchers at Cincinnati Children’s Hospital Medical Center honed in on the interaction of these molecules (histamine and IL-4) and the VE barrier function within blood cells during anaphylaxis.

Researchers found that anaphylaxis is linked with the disruption of the VE barrier integrity. They found that higher levels of histamine and IL-4 resulted in an increase of fluid loss from blood vessels and into surrounding tissues, which influenced the severity of anaphylaxis. This finding suggests that the activity of the IL-4 receptor plays a role in the severity of fluid loss, which may be helpful where anaphylactic symptoms are concerned.

Pharmaceuticals that are formulated to target these proteins may be able to moderate allergic reactions, potentially lowering the threat of symptoms of anaphylaxis. One drug has already been approved to treat moderate to severe eczema. Hogan also hopes this research will play a role in preventing severe allergic reactions during immunotherapy.

This research study was published in the Journal of Allergy and Clinical Immunology.


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