Susan L. Hefle

An evaluation of the sensitivity of subjects with peanut allergy to very low doses of peanut protein: A randomized, double-blind, placebo-controlled food challenge study☆☆☆★

BACKGROUND The minimum dose of food protein to which subjects with food allergy have reacted in double-blind, placebo-controlled food challenges is between 50 and 100 mg. However, subjects with peanut allergy often report severe reactions after minimal contact with peanuts, even through intact skin. OBJECTIVE We sought to determine whether adults previously proven by challenge to be allergic to peanut react to very low doses of peanut protein. METHODS We used a randomized, double-blind, placebo-controlled food challenge of 14 subjects allergic to peanuts with doses of peanut ranging from 10 microg to 50 mg, administered in the form of a commercially available peanut flour. RESULTS One subject had a systemic reaction to 5 mg of peanut protein, and two subjects had mild objective reactions to 2 mg and 50 mg of peanut protein, respectively. Five subjects had mild subjective reactions (1 to 5 mg and 4 to 50 mg). All subjects with convincing objective reactions had short-lived subjective reactions to preceding doses, as low as 100 microg in two cases. Five subjects did not react to any dose up to 50 mg. CONCLUSION Even in a group of well-characterized, highly sensitive subjects with peanut allergy, the threshold dose of peanut protein varies. As little as 100 microg of peanut protein provokes symptoms in some subjects with peanut allergy.

A consensus protocol for the determination of the threshold doses for allergenic foods: how much is too much?

Background While the ingestion of small amounts of an offending food can elicit adverse reactions in individuals with IgE‐mediated food allergies, little information is known regarding these threshold doses for specific allergenic foods. While low‐dose challenge trials have been conducted on an appreciable number of allergic individuals, a variety of different clinical protocols were used making the estimation of the threshold dose very difficult.

Peanut allergen Ara h 3: Isolation from peanuts and biochemical characterization

Background:  Peanut allergen Ara h 3 has been the subject of investigation for the last few years. The reported data strongly depend on recombinant Ara h 3, since a purification protocol for Ara h 3 from peanuts was not available.

Presentation of allergen in different food preparations affects the nature of the allergic reaction--a case series.

Background Characterization of fatal and non‐fatal reactions to food indicates that the majority of reactions are due to the ingestion of prepared foods rather than the non‐processed allergen. In an ongoing study that used a double‐blind placebo‐controlled food challenge to investigate peanut allergy and clinical symptoms, the observed reaction severity in four of the first six subjects was greater than anticipated. We hypothesized that this was due to differences in the composition of the challenge vehicle.

Does skin prick test reactivity to purified allergens correlate with clinical severity of peanut allergy

Background Recognition of specific peanut allergens or the diversity of IgE binding to peanut allergens may play a role in the elicitation of severe allergic reactions.

The range of minimum provoking doses in hazelnut-allergic patients as determined by double-blind, placebo-controlled food challenges

Background The risk for allergic reactions depends on the sensitivity of individuals and the quantities of offending food ingested. The sensitivity varies among allergic individuals, as does the threshold dose of a food allergen capable of inducing an allergic reaction.

Purification and immunoglobulin E-binding properties of peanut allergen Ara h 6: Evidence for cross-reactivity with Ara h 2

Background IgE‐binding peanut proteins smaller than 15 kDa were previously identified as potential allergens in the majority of our peanut allergic population.

Digestion of peanut allergens Ara h 1, Ara h 2, Ara h 3, and Ara h 6: A comparative in vitro study and partial characterization of digestion-resistant peptides

SCOPE There are differences in stability to pepsin between the major allergens in peanut; however, data are from different reports using different digestion models. This study provides a comprehensive comparison of the digestibility of the major peanut allergens. METHODS AND RESULTS Peanut allergens Ara h 1, Ara h 2, Ara h 3 and Ara h 6 were incubated with pepsin to mimic the effect of gastric digestion. Samples were analyzed using SDS-PAGE. To further investigate resistance to digestion, Ara h 2 was additionally subjected to digestion with trypsin and residual peptides were characterized. Ara h 1 and Ara h 3 were rapidly hydrolyzed by pepsin. On the contrary, Ara h 2 and Ara h 6 were resistant to pepsin digestion, even at very high concentrations of pepsin. In fact, limited proteolysis could only be demonstrated by SDS-PAGE performed under reducing conditions, indicating an important role for the disulfide bridges in maintaining the quaternary structure of Ara h 2 and Ara h 6. Trypsin digestion of Ara h 2 similarly resulted in large residual peptides and these were identified. CONCLUSION Ara h 2 and Ara h 6 are considerably more stable towards digestion than Ara h 1 and Ara h 3.

Assessing Genetically Modified Crops to Minimize the Risk of Increased Food Allergy: A Review

The first genetically modified (GM) crops approved for food use (tomato and soybean) were evaluated for safety by the United States Food and Drug Administration prior to commercial production. Among other factors, those products and all additional GM crops that have been grown commercially have been evaluated for potential increases in allergenic properties using methods that are consistent with the current understanding of food allergens and knowledge regarding the prediction of allergenic activity. Although there have been refinements, the key aspects of the evaluation have not changed. The allergenic properties of the gene donor and the host (recipient) organisms are considered in determining the appropriate testing strategy. The amino acid sequence of the encoded protein is compared to all known allergens to determine whether the protein is a known allergen or is sufficiently similar to any known allergen to indicate an increased probability of allergic cross-reactivity. Stability of the protein in the presence of acid with the stomach protease pepsin is tested as a risk factor for food allergenicity. In vitro or in vivo human IgE binding are tested when appropriate, if the gene donor is an allergen or the sequence of the protein is similar to an allergen. Serum donors and skin test subjects are selected based on their proven allergic responses to the gene donor or to material containing the allergen that was matched in sequence. While some scientists and regulators have suggested using animal models, performing broadly targeted serum IgE testing or extensive pre- or post-market clinical tests, current evidence does not support these tests as being predictive or practical. Based on the evidence to date, the current assessment process has worked well to prevent the unintended introduction of allergens in commercial GM crops.

Food allergen labeling in the USA and Europe.

Purpose of review The ingredient statement on the label of packaged foods is an important source of information for food-allergic consumers. New legislation in the USA and European Union will increase the amount of information available to food-allergic consumers. Recent findings The USA has implemented the Food Allergen Labeling & Consumer Protection Act, which mandates use of clear labeling and source labeling of ingredients derived from commonly allergenic sources. Similarly, the European Union is implementing new regulations that mandate the source labeling of ingredients derived from commonly allergenic foods and fuller disclosure of allergenic food components, even when present in small amounts. The food industry is providing consumers with information relating to the presence of allergenic residues by adding voluntary advisory statements, such as ‘may contain peanuts’. Summary Food-allergic consumers are advised to follow specific strict avoidance diets that exclude allergenic foods and ingredients derived from these foods. Thus individuals must avoid potentially hazardous residues of the allergenic food that might occur as the result of common practices in the food industry. The ingredient statement on packaged food labels now contains more information than ever before.