Les allergènes du grain de blé

Wheat is a major dietary cereal, which can cause respiratory, contact and food allergies. Wheat grain contains a large panel of proteins with very particular structures and functions. This review will consider diverse wheat grain proteins and summarize recent work on wheat grain allergens.     

Console de jeu : mode de transmission de l'allergie à l'arachide

The authors report the case of a child allergic to peanuts since he was one year old who, at the age of 9 years, developed angioedema after playing with his "Play Station". This device had been used previously by his uncle who had eaten peanuts at a family get-together. This observation illustrates a new way of transmitting food allergies and provides an opportunity to review the principal situations in which this allergy can be transmitted by proxy.     

Histoire de l'allergie alimentaire : des précurseurs à l'histoire contemporaine

Food allergies are an important public health problem. Relatively unheard of during the 1970–1980 s, they had almost always been associated with the same allergens (cow milk, chicken eggs, and fish). Since then, they have become more frequent and more varied, involving about 4% of the general population of all ages; the prevalence may even be 5–6% or more among children. They are also becoming more and more severe, and interfering more in daily living. Beginning in the 1980 s, the story of food allergy has been marked by the explosion of the occurrence of peanut allergy, the prevalence of which has at least doubled over the past five years. Another important tendency has been an increase in the frequency of allergy to shelled fruits (e.g. exotic nuts) and to certain plant allergens (e.g. sesame, buckwheat and wheat). There has also been an increase in the number of near-fatal and fatal cases of food-related anaphylaxis, justifying the establishment of a monitoring network. The workup of food allergies has become more standardized, allowing a definitive diagnosis to be more easily established, thus justifying avoidance of the responsible substance. Indeed, until recently, in the absence of effective preventive measures and a good risk-benefit ratio, the prevention of food allergies depended on avoidance of the responsible food(s), which recommendation is nevertheless often not followed as prescribed. Other preventive measures (antihistamines, corticosteroids, adrenalin auto-injectors) are then adopted to avoid recurrences, which can be considered as evidence of treatment failure. Recent years have been marked by standardization of preventive measures based on the Project of Individual Care and by the establishment of educational protocols. The future may see the development of specific immunotherapy (until now, difficult and dangerous), modification of food allergens, and treatments that block IgE-dependant allergic reactions. For example, the preliminary results of a clinical trial of sublingual immunotherapy with hazelnut appear to be promising. Considering the difficulty of diagnosis and prevention, the social and psychological repercussions of food allergies are considerable for both children and their families.     

Immunothérapie et allergie alimentaire

Immunotherapy trials on food allergy were published some years ago and few of them were randomized. The protocols used varied and IgE-mediated food allergies were the first studied. Immunotherapy is mainly indicated for persistent food allergy after the usual age of recovery. Other factors, such as the dose of the allergen and the nature of the symptoms due to food allergy, are less well-defined with regard to indications for immunotherapy. Different techniques are available: the subcutaneous route, with well-known adverse effects when currently available extracts are used; the oral route, with efficacy in a third of the cases and the sublingual route, which seems to be promising. The real effect of immunotherapy, whether persistent, transitory or merely an increase in the amount of food tolerated, remains to be defined.     

Allergie aux protéines du lait et aux hydrolysats de protéines de lait : à propos d'une observation au diagnostic retardé

The authors report the case of an infant with a history of eczema due to cow milk and who later had two bouts of urticaria after drinking milk protein hydrolysate. The particular interest in this case is the disconnection between the onset of the eczema (when an allergy workup was not predictive) and the subsequent finding, one year later, of positive IgE-dependant sensitization tests.     

Test de provocation par voie orale aux aliments chez l'enfant. Quand,pour qui et comment ? Interprétation

Oral food challenges (OFC) have to be carefully interpreted. OFC prove the food allergy or persistent food allergy. OFC prove also the absence or the cure of food allergy. Objective and subjective signs are distinguished. Cutaneous and gastrointestinal symptoms are more frequent than respiratory or systemic symptoms. Delayed reactions, isolated or associated, have to be taken into account. In some cases, the OFC cannot be interpreted. Negative double-blind placebo-controlled food challenge must be confirmed by an open manner.     

Allergologie et auto-immunité : médecine interne aux frontières de l'allergologie

At the crossroad of numerous medical specialties, Internal Medicine incorporates a number of different fields, including autoimmune diseases and other immunological conditions, the symptoms of which can simulate those of allergies, particularly allergies of the skin and lungs. We will limit our discussion to only a few aspects of this subject: 1) concerning immunological aspects, CD4+ IL17+ lymphocytes and the detection of autoantibodies in chronic urticaria; 2) concerning pharmacological aspects, discussion of the eventual role of acetaminophen in the recent increase in the frequency of asthma and allergic diseases; and 3) concerning other clinical matters, mastocytosis and insect stings, eosinophilic esophagitis, mosquito bites, allergy and NK lymphoma.     

Définitions des termes utilisés en allergologie alimentaire chez l’enfant

In so far as there are no recent medical references that specify terms used in allergy, and particularly terms dealing with food allergy, it seemed to us that it would be of use to compile a glossary that would be helpful in daily practice. The defined terms (plus comments) have been retained according to sequences that correspond to steps in a food allergy work-up. The following terms are entered successively in this review: atopic dermatitis; SCORAD; asthma; pulmonary function tests; medications for children; symptoms and severity of food allergies; immediate skin tests; intradermal tests or “atopy patch-tests”; allergen-specific and total serum IgE levels; oral provocation test; labial provocation test; other tests used in allergy work-ups; allergy, hypersensitivity, atopy; allergens, allergies, sensitizations, allergic cross-reactions; treatment of an allergic reaction.     

Épidémiologie de l’allergie alimentaire

The epidemiology of food allergy normally relies on surveys using questionnaire in general populations and studies on cohorts and through professionals in allergy clinics, sometimes completed by prick-tests, specific IgE assays and/or oral challenges. Complementary data are supplied by specialized medical networks. In European countries, the prevalence of food allergy in the pediatric population is about 4.7%, and in adults it is about 3.2%. Striking disparities characterize the response to questionnaires in EU countries. Life-threatening anaphylaxis occurs in 1/10,000 inhabitants, fatal anaphylaxis in 1/1 million inhabitants. A drastic increase of life-threatening and lethal anaphylaxis has been noted in the UK and Australia over the past ten years. In France, there has been an increase of 28% between 2001 and 2006. The Allergy Vigilance Network, which includes 400 allergists, reports that this increase has occurred in the pediatric population. The prevalence of food allergies depends on age and consuming habits. Milk, egg, peanut and tree-nuts are at the top of the list in children. Prunoïdeae, latex-group fruits, Apiaceae, wheat and tree-nuts are the most important food allergens in adults. Peanut and tree nuts are the main offending allergens in severe anaphylactic cases. Since 2002 the Allergy Vigilance Network in France and Belgium has been identifying newly-appearing dangerous allergens. Molluscs, lupine flour and cashew nuts are the most common on this list and labelling these foods is now compulsory. Goat and sheep milk proteins (14 cases), buckwheat (25 cases) and wheat isolates are not yet required to be labelled. The danger of anaphylaxis to goat and sheep proteins (two deaths out of 14 cases) is due to the likelihood of their being masked allergens, for which reason the EU Scientific Agency should be made aware of the necessity of required labelling of foods containing these substances.     

Facteurs de risque de l’allergie alimentaire sévère

Asthma is the main risk factor for severe, potentially fatal food allergy reactions. Peanut and tree nuts are the main foods involved in these reactions. Consequently, any asthmatic individual with a food allergy must be controlled perfectly by daily treatment. Other risk factors for severe allergic reactions are parallel medications (especially aspirin, beta-blockers and angiotensin enzyme inhibitors), physical effort, food consumption outside the home, mastocytosis, hidden allergens, and a combination of such associated factors. Better patient education and, in addition, risk prevention, particularly away from home, in restaurants and at school, should reduce the frequency of severe food allergic reactions. Collection of data concerning food allergies will allow better identification of the individuals at risk and development of targeted preventive measures.     

Quoi de neuf en allergologie pédiatrique en 2005 ? Partie 4. Allergie cutanée,alimentaire, médicamenteuse et aux insectes (Une revue de la littérature internationale d'octobre 2004 à octobre 2005)

Allergological work-up and treatment of french children with atopic dermatitis have been the subject of a recent consensus. Food avoidance is useless for prevention of atopic dermatitis, and should be indicated in children with severe atopic dermatitis associated with food allergy only. Exposure, sensitization and allergy rates to nuts increase with age, and avoidance of nuts (even tolerated) is recommended in young children allergic to one or several nuts to prevent the risk of sensitization and allergy to an increasing number of nuts. Threshold values of skin prick-tests and specific IgE determinations with a 90-100% predictive value for food allergy are highly variable from one study to another one, and depend on numerous factors such as age of the children, the allergens used, etc. The diagnostic value of patch-tests and skin application food tests remains controversial. Treatment of food allergy is based on the eviction of the allergenic foods. However, probiotics and « desensitization » to foods may be efficacious in some patients. In children that have outgrown their food allergy, tolerance should be maintened by regular consumption of the foods. However, the parents should be informed that relapses requiring an emergency treatment may occur. Finallly, in children as in adults, repeated mosquito bites induce a desensitization, and most children outgrow their allergy between five to fourteen years.     

Induction de tolérance orale aux aliments chez l’enfant : aspects pratiques

Specific oral tolerance induction (SOTI) to food is a new topical-therapeutic approach of food allergy. When successful, it improves significantly the patients’ quality of life. SOTI’s practical aspects for child are discussed from our recent experience concerning cow milk, hen’s egg and wheat. Family’s motivation and education are crucial questions to achieve SOTI correctly. A detailed information of possible side effects is essential.     

Test de provocation par voie orale aux aliments chez l'enfant. Quand,pour qui et comment ? Conséquences

Whatever results are, oral food challenges (OFC) will have consequences, particularly on diet and emergency kit. Positive OFC, negative OFC and food specificities are discussed, according to the literature review. In case of positive OFC, the management and monitoring of persistent food allergy is specified. Practical recommendations are suggested.     

Quoi de neuf en allergologie pédiatrique en 2006-2007 ? Partie 3: Allergie cutanée, alimentaire, médicamenteuse et aux insectes (une revue de la littérature internationale d’octobre 2005 à septembre 2007)

Most sensitizations in children with atopic dermatitis are non pathogenic. Thus, responses in prick-tests, specific IgE determinations and patch-tests should be carefully evaluated based on the clinical history of the children or responses in challenge tests. Moreover, although atopy patch-tests are highly specific, they have a low sensitivity. Food eviction is indicated in a few children only, since they may be responsible for anaphylactic reactions induced by accidental ingestion of the food or oral challenge tests. The predictive value of serum specific IgE to foods depends on the food investigated, the age of the children, their allergic disease (atopic dermatitis, urticaria/angioedema, anaphylaxis) and, may be, on their ethnical origin. The prevention of food-induced severe reactions is based on eviction. However, several studies suggest that oral desensitization to foods may be efficient. Most frequent reactions in children hypersensitive to antalgics, antipyretics and nonsteroidal antiinflammatory drugs are oedema (facial oedema especially) and urticaria. Usually, the severity of the reactions increases from one treatment to another one and with the dose of drug administered to the children. Diagnosis is based on a convincing clinical history or on challenge tests. Skin tests with vaccines should be performed according to a standardized procedure because they may give false positive responses. Most latex sensitizations detected by skin prick-tests and, especially, specific IgE determinations are non pathogenic. The prevention of reactions to latex is based on eviction. However, preliminary results suggest that sublingual desensitization with a latex extract is efficient and well-tolerated.     

L'allergie au tournesol et à son huile : rôles du contact,de l'ingestion et de l'inhalation

We report the case of a 5-years old girl with food allergy to sunflower oil. Sensitivity to sunflower oil and seeds was demonstrated by skin tests whereas assays of serum for sunflower-specific IgE were negative. An oral challenge test with 54 ml of sunflower oil was positive. The patient also reacted to cutaneous contact and inhalation of sunflower seeds. Depending on the route of contact –– skin contact, ingestion or inhalation –– sunflower oil and seeds can trigger symptoms such as urticaria, erythema, vomiting, dyspnea or fatigue.     

Axes de recherche en allergologie alimentaire : hypoallergénicité et vaccins

The frequency of food allergy in the pediatric population (8%), as well as the worrying increase of prevalence of severe anaphylaxis boost the research for means of prevention and for therapeutics alternative to the sole eviction of foods. Oral desensitization and sublingual immunotherapy, being the main part of the present clinical research are not in the scope of this review. Future trends of research focus on hypoallergenicity and vaccines. The definition of hypoallergenicity is limited to a lesser reactivity because of a lesser binding of specific IgE to modified food allergens, since the conditions of the immunogenicity leading to sensitization remain unknown. Different ways for patients, alimentary industry and agronomical research are detailed: heating and cooking, enzymatic and chemical treatment of natural foods, physical treatments (texturization, ultrafiltration,…), screening of natural varieties in order to characterize some of them with a lower level or an absence of major allergens. Bioengineering of plants with a reduced level of major allergens, and site-directed mutagenesis on B epitopes could be helpful for a safer nutrition and vaccines. Possible molecular forms aimed at vaccines are considered: recombinant natural allergens, modified recombinant allergens by dimerisation, site-directed mutagenesis, fusion with other molecules, long peptides,… Associated considerations are the choice of adjuvants promoting a Th1 response, as well as vectors for the expression of recombinant food allergens: bacteria, probiotic ones, or poorly allergenic plants. Mucosal vaccines could be especially interesting for food allergens in order to add specific mechanisms of tolerance arising in the intestinal mucosa to the reorientation towards a Th1 and TREG response. Plasmidic DNA vaccines and anti-IgE vaccines are an object of research without any application in the near future. Therapeutic vaccines for food allergens might be substituted to oral desensitization and could be applied first to peanut allergy and to cross allergy between pollens and fruit or vegetable linked to panallergens. Prophylactic vaccines might be a second step for atopic infants, insofar as more knowledge could be obtained of mechanisms and enhancing factors of oral tolerance to food allergens and the “opportunity window” for the establishment of oral tolerance.     

Modèles animaux d’allergie alimentaire. Application aux protéines de blé

The allergens responsible for wheat food allergy are beginning to be characterized. Nevertheless, animal models that produce highly-specific IgE and clinical symptoms comparable to those observed in allergic patients are of great interest for precise studies of allergens and of the mechanisms involved in wheat allergy. The aim of our research was to develop, in the first instance, a mouse model of allergy to a total extract of gliadins, then to use this model to study two major wheat allergens involved in wheat food allergy on children and adults, namely, the lipid-transfer protein (LTP) and the omega-5 gliadins.

Methods

First, we determined the mouse strain and the allergen dose required to induce an optimal allergic reaction to wheat. Three strains of mice (Balb/cJ, B 10.A ND c3 h/hEj) received four successive intraperitoneal injections of a total-gliadin extract (10 or 20 μg) adsorbed on alum. The level of sensitization was determined by assay of gliadin-specific IgE and IgG1 and by the level of cytokines secreted by splenocytes activated in vivo by the gliadins; in vitro basophil (RBL) degranulation tests were also done. In addition, the intensity of the allergic reaction was evaluated in vivo by analysis of the production of type Th2 cytokines and the influx of eosinophils in bronchoalveolar fluid (BAF) after intranasal gliadin extract provocation. Sensitization assays and provocation tests with LTP and omega-5 gliadins were done subsequently.

Results

The highest level of sensitization was observed in the Balb/cJ mice, whatever the dose of gliadins used. After the provocation test, these mice developed an intense-allergic reaction, as demonstrated by the strong production of type Th2 cytokines and the influx of eosinophils in the BAF. In contrast, a weak or no reaction was observed in the other two mouse strains. While sensitization of Balb/cJ mice by omega-5 gliadins was not very effective, administration of LTP induced significant production of specific IgE and IgG1 as well as specific degranulation of RBL cells, but little or no secretion of type Th2 cytokines by activated splenocytes. Induction of an allergic response after intranasal introduction of LTP was not very effective, in spite of the cellular influx in the BAF.

Conclusion

Balb/cJ mice, sensitized by intraperitoneal injection of a total-gliadin extract, appeared to produce some of the markers of wheat allergy, but the results of the sensitization studies with the purified allergens appear to be more complex.     

Détermination des seuils de réactivité au cours des allergies alimentaires

It is important for an individual allergic to food to be aware of the threshold (the minimal amount) of the allergenic food that can trigger a reaction. This information is equally essential to the food-processing industry for labeling of pre-packaged foodstuffs. Three methods are available to determine the threshold: case reports, statistical methods and oral provocation tests. Published data available at present allow only limited analysis for three foods (cow milk, chicken egg and peanut). In addition, the absence of standardized oral provocation tests limits determination of thresholds.     

De l'importance de lire attentivement les étiquettes avant de consommer… des spaghettis

Three children who knew that they were allergic to peanuts and who knew how to avoid exposure to peanuts nevertheless had an immediate allergic reaction shortly after eating spaghetti with tomato sauce. These observations give us the chance to discuss how to manage the food intake, especially concerning all kinds of nuts, of children with peanut allergy, the new European rules dealing with labelling, and to stress the absolute necessity to read carefully the labels of all products consumed by individuals with food allergy, even if the allergy concerns products containing ingredients to which the individual is not known to be allergic.