In small study, nearly all people who stopped eating the legumes daily later experienced allergic reaction
Peanut allergy is proving a tough nut to crack. Many people seem able to overcome the allergy by consuming tiny-but-increasing amounts of the legume daily for months or years. But the protection often evaporates if they fail to keep eating peanuts regularly, a new study shows. Twenty people with the allergy could eat a handful of peanuts after two years of bit-by-bit consumption, but 17 of them relapsed after avoiding peanuts for several months and then trying to eat some.
Blood tests of the volunteers suggest that those who fared best developed an army of immune stalwarts called regulatory T cells, or T-regs, which were oriented toward cooling immune reactions toward peanut protein. The researchers also report that this still-experimental introduction of peanuts into the diet, called oral immunotherapy, seems to induce biochemical changes in T-regs that might drive some of the newfound protection. The report appears in the February Journal of Allergy and Clinical Immunology.
Kari Nadeau, a pediatrician and immunologist at Stanford University School of Medicine, and her colleagues tracked the progress of 23 people with a peanut allergy as they consumed peanut protein powder over two years — starting with 1 milligram per day and working up to 4,000 milligrams. Three people dropped out of the study. After two years, the remaining 20 people could eat a handful of peanuts without a reaction.
As part of the study, the volunteers then gave up peanuts for three months. The next time they consumed peanuts, under supervision, 13 had allergic reactions but seven were fine. After those seven went without peanuts for another three months, four failed another peanut test.
The researchers examined blood from the study participants and from other allergic people, who were not getting oral immunotherapy. All 20 immunotherapy volunteers experienced a clear increase in numbers of T-regs during the two years, while the untreated people didn’t. And the seven volunteers who went on to remain tolerant to peanuts after the three-month hiatus produced more T-regs throughout the study than did the other participants.
The researchers also measured indicators of the T-reg cells’ production of a protein called Foxp3, which tones down overzealous immune reactions. All volunteers started out with signs of low levels of the protein. The seven people who maintained normal immunity through the first three-month hiatus showed evidence of more Foxp3 in their T-regs at the two-year mark than the other volunteers did.
At the start of the study, all volunteers had alterations called epigenetic changes on the gene encoding Foxp3 in T-regs. These changes showed up as the addition of chemical groups that bog down the gene’s activity. As the participants became less allergic during the two years, these changes faded. But the alterations lingered more in people who would later lose their ability to eat peanuts during the first three-month hiatus.
While oral immunotherapy continues to be the most promising line of research for food allergy treatment, the new study suggests that “the durability of this effect is relatively marginal in most people,” says Calman Prussin, a physician and allergy researcher at the National Institute of Allergy and Infectious Diseases in Bethesda, Md.
But, he adds, “this study underscores that it’s a good idea to try to develop a way to amplify the T-reg response.” A goal might be to find a way to ensure that all patients achieve the long-term T-reg protection that only a few participants experienced in the study.
Nadeau says the new findings also suggest that T-regs might serve as indicators of patients who could get by without eating peanuts daily. But food allergy is a complex business involving antibodies, immune proteins and more than 30 kinds of immune cells, she says. “To think any one cell is the biomarker,” she says, “is a little premature. We’re getting little pieces of the puzzle together.”
A. Syed et al. Peanut oral immunotherapy results in increased antigen-induced regulatory T-cell function and hypomethylation of forkhead box protein 3 (Foxp3). Journal of Allergy and Clinical Immunology. Vol. 133, February 2014, p. 500. doi: 10.1016/j.jaci.2013.12.1037.
N. Seppa. Therapy for milk allergy offers hope, and caution. Science News Online, February 27, 2013.
L. Beil. Little by Little. Science News. Vol. 176, September 12, 2009, p. 20.
H.A. Sampson. Peanut oral immunotherapy: Is it ready for clinical practice? Journal of Allergy and Clinical Immunology: In Practice. Vol. 1, January 2013, p. 15. doi: 10.1016/j.jaip.2012.10.009.
P. Varshney et al. A randomized controlled study of peanut oral immunotherapy: Clinical desensitization and modulation of the allergic response. Journal of Allergy and Clinical Immunology. Vol. 127, March 2011, p. 654. doi:10.1016/j.jaci.2010.12.1111.
A. Thyagarajan et al. Peanut oral immunotherapy (OIT) is not ready for clinical use.
Journal of Allergy and Clinical Immunology. Vol. 126, July 2010, p. 31. doi: 10.1016/j.jaci.2010.05.012.
S.M. Jones et al. Clinical efficacy and immune regulation with peanut oral immunotherapy. Journal of Allergy and Clinical Immunology. Vol. 124, August 2009, p. 292. doi: 10.1016/j.jaci.2009.05.022.