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Genetic basis for allergies discovered

Researchers at the School of Medicine’s Nadeau Lab and the Lucile Packard Children’s Hospital have found that peanut-allergic patients who have undergone desensitization treatment have altered DNA methylation levels, offering the potential to use those levels as markers for patients undergoing other allergy therapies.

Holden Maecker Ph.D. ‘88 P.D. ‘88 P.D. ‘94, director of the Human Immune Monitoring Center and a co-author of the paper, explained that the fraction of children who have peanut allergies has risen over time.

“Some of them have a severe peanut allergy, and it’s life threatening for them,” Maecker said. “It’s an emerging medical problem.”

Similar to other food allergies, peanut allergies currently have no cure. Desensitization—a method of treatment under which patients are given increasing doses of peanut powder every day over a two-year period—has allowed patients to tolerate higher amounts of peanut after 24 months, but the extent to which continued treatment is necessary remains uncertain.

“One thing people ask when they finish the study is, ‘Does this mean I have to take peanut butter at four grams a day every day for the rest of my life?’” said Kari Nadeau, associate professor of pediatrics, immunology and allergy and the paper’s senior author.

The researchers studied patients who had ingested peanut powder daily for 24 months, measuring their reactions to peanuts three months after the treatment concluded. Of the 20 patients who completed the program, seven were no longer reactive and were deemed “tolerant.” The remaining thirteen were reactive only to higher levels of peanut than patients who had not gone through desensitization.

Researchers studied the blood samples of the more tolerant patients and found that the DNA of their regulatory T cells—cells known to suppress immune response—had fewer methyl groups attached to them. This change in methylation was located at a gene called FOXP3, which plays a role in allergic responses.

Researchers plan to next undertake a larger phase-two study involving about 120 people. By looking at different combinations of gene markers and cells, they hope to find a composite indicator that may predict the effectiveness of immunotherapy in a patient.

“In the new studies that we’re starting…we’re going to look for the same thing, but we’re also going to look for other changes that accompany it,” Maecker said. “There’s certainly the possibility that, in different people, tolerance [to peanuts] is induced by different mechanisms.”

The Nadeau Lab published their research online on Jan. 31 in the Journal of Allergy and Clinical Immunology.

 

Contact Issa Yousif at iyousif ‘at’ stanford ‘dot’ edu.