Report from AAAAI: New Targets and Tools for Food Allergy Diagnosis and Treatment
Continuing FARE’s reporting from this year’s annual scientific meeting of the American Academy of Allergy, Asthma & Immunology (AAAAI), we’re proud to share that research co-funded by FARE was featured in a number of AAAAI 2017 poster sessions. FARE is the world’s largest private funder of food allergy research. From fundamental laboratory studies in animal models to patient diagnosis and clinical trials, FARE funding helps drive advances in all areas of food allergy research. Some examples include:
Targeting pathways to lessen severity of anaphylaxis: During severe anaphylaxis, fluid can leak from blood vessels, concentrating the blood cells and causing low blood pressure and shock. This symptom is also seen in mice when researchers trigger a systemic reaction. Another reaction symptom measurable in mouse is a drop in the body temperature (hypothermia). A small signaling protein called IL-4 –interleukin-4 enhances these symptoms.
Binding of IL-4 to the IL-4 receptor protein on cell surfaces promotes immune responses that are associated with allergy. To explore the role of the IL-4 receptor in anaphylaxis, investigators at Cincinnati Children’s Hospital genetically engineered mice that are missing a piece of the receptor. Sensitized mice that are challenged with food protein have more severe symptoms when treated with IL-4, but in mutant mice with non-functional IL-4 receptors, reaction symptoms are unaffected by IL-4 treatment. Tests using cultured cells confirm that the IL-4 receptor must be functional for IL-4 to increase the permeability of histamine-treated cells of the blood vessel lining.
Identifying the molecular events that lead from allergen exposure to anaphylaxis can provide targets for drug therapies. The IL-4 receptor is a target of the drug Dupilumab, which has performed well in clinical trials to treat atopic dermatitis. These results suggest that Dupilumab may find future use in the treatment of food allergy. This poster received special recognition from AAAAI’s Food Allergy, Dermatologic Diseases, and Anaphylaxis interest section.
Blood samples were taken prior to an oral food challenge assessing eligibility to participate in a clinical trial of peanut oral immunotherapy (OIT). Patients eligible for the trial, defined here as “reactors,” were unable to tolerate a single 100-mg dose. The “non-reactors,” patients who tolerated 100 mg peanut protein in a single dose, were excluded from the trial.
Blood samples from the two patient groups, reactors and non-reactors, were studied by researchers at Benaroya Institute in Seattle to learn more about some of the T cells that are activated by peanut protein in peanut-allergic patients. T cells are a diverse group of cells that perform many immune functions. Th2 cells that are specifically activated by food proteins are associated with food allergy.
Analysis of individual T cells and the proteins they produce in response to peanut revealed that the peanut-activated T cells of reactors clustered into two distinct groups. Peanut-specific T-cells from one group of reactors resembled the Th2 cells associated with allergic conditions, while peanut-specific T-cells from the second group of reactors were characterized by a different set of proteins. Non-reactor patients who tolerated a 100-mg dose had fewer peanut-activated T cells, and the proteins produced by those cells more closely resembled the T-cell proteins of individuals who do not have peanut allergy.
In the context of the ongoing clinical trial, researchers are eager to learn whether patients with different T cell profiles respond differently to peanut OIT. The ability to “fingerprint” a patient’s immune response to peanut may someday allow clinicians to pinpoint which interventions will be most effective for that individual.
Basophil activation tests: Basophils are large white blood cells that bind IgE antibodies and contribute to allergic reactions, releasing histamine when activated. Measuring basophil activation may provide a useful tool for diagnosing food allergy. Currently, skin prick tests (SPTs) and blood tests for allergen-specific IgE antibodies (sIgE) show sensitization to foods, but positive sensitization results may not indicate allergy.* Excluding foods on the basis of positive SPT or sIgE results alone can limit childhood nutrition and may even contribute to the development of clinical food allergy.
In basophil activation testing, blood cells are exposed to possible allergens and then labeled to allow detection of allergen-activated proteins. Researchers at National Jewish Health in Colorado found that, in 11 children undergoing allergy testing, basophil activation predicted the outcome of oral food challenges in 30 of 33 tests (91 percent), with one negative test failing to predict peanut allergy and two positive tests failing to predict oral tolerance to milk and peanut. In a case study, a five-year-old child with moderately severe eczema had been placed on an elimination diet for peanut, wheat, soy, oat, rice, egg, tree nuts and sesame based on sIgE levels. The results of the child’s basophil activation tests matched his food challenge results, which showed that he could tolerate eating milk, soy, wheat and several tree nuts, all of which had yielded positive SPTs. Work is ongoing to develop a more stable version of the basophil activation test that can be performed more than four hours after the blood is drawn.
*For example, the LEAP study included infants whose initial SPTs resulted in wheals measuring 1 - 4 millimeters in diameter, but among these peanut-sensitized infants who regularly ate peanut from an early age, only 11 percent developed clinical peanut allergy.