A Mutation for Allergies

Scientists have found a genetic flaw that appears to make some people more susceptible to allergies than others. The discovery, reported in tomorrow's New England Journal of Medicine, may allow doctors to identify allergy-prone individuals and might help researchers tease out the causes of different kinds of allergic diseases, from skin rashes to asthma.

Allergies develop when the immune system mistakenly reacts to relatively benign substances, such as peanut proteins or penicillin. In the hunt for genetic and environmental factors responsible for allergies, a prime suspect has been interleukin-4 (IL-4); this immune system protein tells white blood cells to make IgE antibodies, which recognize foreign substances and set off an immune attack.

Pediatric immunologists Gurjit Khurana Hershey and Talal Chatila of the Washington University School of Medicine in St. Louis and their colleagues set out to examine the receptor protein that IL-4 binds to on white blood cells. They sequenced the gene coding for the receptor in patients with either severe skin allergies or hyper-IgE syndrome, a rare condition in which the body produces too much IgE. They found an identical genetic mutation in seven of their 10 patients. Next, they tested 50 healthy adults for both the mutation and for above-average IgE levels. They found the mutation in 13 of 20 people with elevated IgE levels, but only in five of 30 people with normal IgE levels. Test tube experiments showed that white blood cells with the mutation responded more strongly to Il-4 than did normal cells.

The researchers conclude that the mutated gene likely plays a key role in predisposing people to allergy. Allergist William Cookson of Oxford University agrees. "It does look like a real effect," he says, although he cautions that the results should be replicated with more subjects. If the association holds up in larger studies, Chatila says, doctors could use the information to sort out which mutation--or combination of mutations--leads to different kinds of allergic diseases.