Allergic reaction to peanuts can be blocked

By blocking an enzyme’s activity that is essential to the allergic reaction to peanuts, researchers at National Jewish Health have prevented diarrhoea and inflammation, and reduced levels of several proteins associated with allergies in sensitised mice.

The findings, published online in the Journal of Allergy and Clinical Immunology, identify the enzyme, known as Cyp11a1, as a potential target for treatment of increasingly common and potentially deadly food allergy.

“Right now, we have no therapy for food allergy other than to avoid the allergenic food,” said senior author, Erwin Gelfand, MD, chair of Pediatrics at National Jewish Health. “In Cyp11a1, we have found an essential enzyme and signalling pathway in the intestinal allergic reaction, which are potential targets for intervention.”

Food allergy has become more common in recent decades, now affecting about 8% of the American population. Among children, peanuts are the most common food allergy and can provoke severe, even life-threatening, allergic reactions. Antihistamines and epinephrine are used in response to allergic reactions but there is no approved therapy for the prevention of allergic reactions to food.

Cyp11a1 promotes the first and rate-limiting step in the production of corticosteroids. These steroids have long been used to treat allergic diseases because they inhibit inflammation associated with the allergic reaction. Evidence in recent years, however, has indicated that corticosteroids may also activate immune cells associated with allergic reactions.

The researchers sensitised mice to peanuts so that they became allergic to the legume. When subsequently fed peanut protein, the mice experienced diarrhoea and inflammation in the small intestine. Levels of Cyp11a1 increased, as did cytokine signalling molecules IL13 and IL17A, which are associated with allergic reactions.

When the researchers used aminoglutethimide (AMG) to inhibit the enzymatic activity of Cyp11a1 in the sensitised mice, it prevented allergic diarrhoea and inflammation, and reduced levels of IL13 and IL17A. It also reduced the conversion of naive T cells into allergic Th2 and Th17 subtypes.

“While we evaluated Cyp11a1 blockade in peanut allergy, it could likely have an effect in the full range of food allergies,” said Dr Gelfand.

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