By monitoring genetic changes during acute peanut-allergy reactions in children, scientists have identified six genes and associated mechanisms that appear to play key roles in driving the response.
A report on the work, led by Icahn School of Medicine at Mount Sinai in New York, NY, was recently published in the journal Nature Communications.
The research took the form of a double-blind, placebo controlled human trial and is the first to comprehensively map changes in gene expression before, during, and after exposure to peanuts.
"This study highlights genes and molecular processes that could be targets for new therapies to treat peanut-allergy reactions," explains senior author Supinda Bunyavanich, a Mount Sinai associate professor in pediatrics and genetics and genomic sciences.
She also suggests that the findings "could be important to understanding how peanut allergy works overall."
Growing public health problem
Peanut allergy is a form of food allergy in which the immune system reacts very strongly to the ingestion of a particular food, even if the ingested amount is very small.
The reaction produces a range of symptoms, including: swelling; hives; difficulty breathing; disruption to heart and circulation and digestive systems; and sometimes, potentially life-threatening anaphylaxis.
Peanut allergy is a growing public health concern in the United States, where the prevalence in children rose from an estimated 0.4 percent in 1999 to 2 percent in 2010.
For most people with peanut allergy, the disease starts in early childhood and stays with them for life.
Although it is the main cause of death from food-related anaphylaxis in the U.S., peanut allergy is very rarely fatal. However, the fear that it can kill is a big factor in the "medical and psychosocial burden of disease."
Peanut vs. placebo
In the new study, Prof. Bunyavanich and colleagues analyzed blood samples collected from 40 children with peanut allergy as they took part in a double-blind trial that compared reactions to peanut with reactions to a placebo.
Double-blind means that neither the participants nor the clinicians that administered the doses knew which were peanut and which were placebo.
The blood samples were collected before, during, and after the "oral food challenge" was administered.
When the food challenge was peanut, the children ingested incremental amounts every 20 minutes until there was an allergic reaction, or until the total amount ingested came to 1.044 grams.
When the food challenge consisted of placebo — in this case, the researchers used oat powder — a similar pattern was followed. The children received peanut and placebo doses on different days.
Allergic reaction driven by six genes
All the blood samples underwent comprehensive genetic analysis — using RNA sequencing technology — to find out which genes and cells were active during the allergic reactions and thus were the most likely to be driving them.
The team identified six genes — "LTB4R, PADI4, IL1R2, PPP1R3D, KLHL2, and ECHDC3" — as key drivers of the signaling networks that are active in a peanut allergy response.
An analysis of the immune cells involved also identified "changes in neutrophil, naive CD4+ T cell, and macrophage populations during peanut challenge," they note.
"We still don't completely understand everything that happens in the body during peanut-allergy reactions. We can use these genes to direct our studies of peanut allergy and hopefully, predict how strongly someone with peanut allergy will react."
Prof. Supinda Bunyavanich
The researchers found the results were the same when the ran the trial with another group of 21 patients with peanut allergy.
They now plan to investigate whether the findings apply to people with allergy to milk, egg, and other foods.