The allergenic significance of legumes

Leguminous are a cheap source of protein that are cultivated practically throughout the world. They are the main source of food in developing countries. In the Mediterranean area and Middle East, the most commonly consumed legumes are lentils and chickpea. In the United States, United Kingdom and south-east Asia, the major legumes involved in food allergy are considered to be peanut and soy bean, respectively. The clinical manifestations of the allergy to legumes are similar for all legumes and range from oral allergy syndrome, urticaria, angioedema, rhinitis and asthmatic crises to anaphylaxis and even death. Legumes have a high degree of immunological cross-reactivity. Severals authors have described cross-reactivity among different legumes and between legumes and various vegetables. The allergenicity of legumes is mainly is mainly related to allergens from the storage proteins of seeds. Vicilins from this group of proteins could be an important common allergen in clinical allergy to legumes. Profilins are considered to be a cause of cross-reactivity among fruits, vegetables and some pollens and are believed to be a panallergen. Other panallergens of increasing importance are lipid transfer proteins. Few studies have assessed the long-term clinical course of allergy to legumes. Novel therapeutic agents are being investigated for the treatment of peanut allergy and these could be applied to other legumes.     

Legume cross-reactivity

Legumes are dicotyledonous plants belonging to the Fabales order. The main distinctive characteristic of which is their fruit (legumen, seeds contained in pods). This botanical order is formed by three families: Mimosaceae, Caesalpiniaceae and Papilionaceae or Fabacea. The Papilionaceae family includes the most important allergenic species: Lens culinaris (lentil), Cicer arietinum (chick-pea), Pisum sátivum (pea), Arachis hipogea (peanut), Phaseolus vulgaris (bean) y Glycine max (soy). Legumes are an important ingredient in the Mediterranean diet. Among Spanish children, sensitivity to legumes is the fifth most prevalent food allergy. Lentil and chick-pea are the most frequent cause of allergic reactions to legumes in Spanish children. Legumes could be involved in severe allergic symptoms. The different legumes have structurally homologous proteins, but they are not all equally allergenic, thus making it difficult to distinguish in vitro and in vivo cross-reactivity. We have demonstrated by skin tests and CAP that most of the patients are sensitised to more than one species. We have demonstrated a great degree of cross-reactivity among lentil, chick-pea, pea and peanut by ELISA inhibition (> 50 % max. inhibition). Unlike the Anglo-Saxons population, this phenomenon implies clinical sensitisation for many Spanish children. The majority of our patients have had symptoms with more than one legume (median 3 legumes). Thirty-nine patients were challenged (open or simple blind) with two or more legumes and 32 (82 %) reacted to two or more legumes: 43,5 % to 3, 25,6 % to 2, 13 % to 4 legumes. Seventy three per cent of the patients challenged with lentil and pea had positive challenge to both, 69,4 % to lentil and chick-pea, 60 % to chick-pea and 64,3 % to lentil, chick-pea and pea simultaneously. Peanut allergy peanut can be associated to allergy to lentil, chick-pea and pea but less frequently. Contrarily, white bean and overall green bean and soy are well tolerated by children allergic to other legumes. In our study, 82 % of the children allergic to legumes had a sensitisation to pollen. Pea and bean are the legumes with more in vitro cross-reactivity with Lolium perenne, Olea europea and Betula alba. This cross-reactivity could be because of common antigenic determinants or due to the coexistence of pollen and legume allergy. Panallergens implication seems to be less probable. It is important to emphasize that in spite of an evident clinical and immunological cross-reactivity, the diagnosis of legume allergy should not be based only on specific IgE tests. The decision to eliminate one legume from the diet should be based on a positive oral food challenge.     

Sensitivity and specificity of food specific IgE and IgG determinations for the diagnosis of food allergy

Among the methods currently used to demonstrate a sensitization to foods, the measurement of food specific IgE antibodies (sIgE) is the most practical but not the most accurate. The "sensitivity" of food sIgE determinations is, for example, suboptimal with unstable allergens in fruits and vegetables that are involved in the (birch) pollen-related immediate oral allergy syndromes. In this particular syndrome the history is often conclusive and can be substantiated by skin prick tests with fresh foods. The "sensitivity" of sIgE tests is much better when sIgE are directed to stable plant or animal food allergens which often cause non-immediate generalized reactions. Foods, usually, contain many different (glyco)proteinic allergens of which some are stable and others not. The "sensitivity" of the sIgE test with a particular food, therefore, varies according to the type of allergen that is recognized by the patient. The "specificity" of sIgE tests with foods is affected by the existence of homologous food allergens which induce cross-reactive IgE that may or may not be clinically relevant. While variable, clinical cross-reactivity is more common among botanically-related fruits, among different nuts, among mammalian foods and among seafood than among cereals, grains and legumes. The "specificity" of food sIgE tests is much better when sIgE are directed to unique non-cross-reactive food allergens. Unfortunately, neither the presence of food sIgE nor its level are predictive of clinical reactivity. The identification of individual allergens in foods and the characterization of the relevant IgE binding sites in these allergens might lead to the development of tests that only measure sIgE to clinical relevant food allergens.     

Seafood allergy

Products of the sea are important source of food. Increase in consumption, due to their nutritive value has also led to a great frequency of reactions, including those that are immunologically mediated. Although hypersensitivity reactions to sea products are often easy to identify and can be confirmed by specific in vitro and in vivo tests, some patients can only be diagnosed by double-blind provocation test against placebo (DBPCFC). An atypical or incomplete clinical history suggests, always, contamination with toxins and/or parasites such as Anisakis. Crossed reactivity between different sea products is frequent. However, there are clinical differences between allergy to molluscs, crustaceans and fishes. From precise evaluation of the reactions to sea produce, will result a reduced and reasoned suppression from this type of allergens at food levels.     

Cross-reactivity between fruit and vegetables

Vegetable foods are the most frequent cause of food allergy after the age of 5 years. The most commonly implicated foods are fruit and dried fruits, followed in Spain by legumes and fresh garden produce. In patients allergic to fruit and garden produce, multiple sensitizations to other vegetable products, whether from the same family or taxonomically unrelated, are frequent, although they do not always share the same clinical expression. Furthermore, more than 75 % of these patients are allergic to pollen, the type of pollen varying in relation to the aerobiology of the area. The basis of these associations among vegetable foods and with pollens lies in the existence of IgE antibodies against "panallergens", which determines cross-reactivity. Panallergens are proteins that are spread throughout the vegetable kingdom and are implicated in important biological functions (generally defense) and consequently their sequences and structures are highly conserved. The three best-known groups are allergens homologous to Bet v 1, profilins, and lipid transfer proteins (LTP). Allergens homologous to Bet v 1 (major birch pollen allergen) constitute a group of defense proteins (PR-10), with a molecular weight of 17 kDa, which behave as major allergens in patients from northern and central Europe with allergy to vegetables associated with birch pollen allergy. In these patients, the primary sensitization seems to be produced through the inhalation route on exposure to birch pollen. The symptomatology characteristically associated with sensitization to this family of allergens is oral allergy syndrome (OAS). Profilins are highly conserved proteins in all eukaryotic organisms and are present in pollen and a wide variety of vegetable foods. They have a molecular weight of 14 kDa and present a high degree of structural homology as well as marked cross-reactivity among one another. The presence of anti-profilin IgE broadens the spectrum of sensitizations to vegetable foods detected through skin tests and/or in vitro tests but whether it correlates with the clinical expression of food allergy is unclear.LTPs are the most commonly implicated allergens in allergy to Rosaceae fruits in patients from the Mediterranean area without birch pollen sensitization. LTPs are a family of 9kDA polypeptides, widely found in the vegetable kingdom and implicated in cuticle formation and defense against pathogens (PR-14). They are thermostable and resistant to pepsin digestion, which makes them potent food allergens and explains the frequent development of systemic symptoms (urticaria, anaphylaxis) in patients allergic to Rosaceae fruits in Spain. LTPs have also been identified in other vegetable foods and in pollens and a marked degree of cross-reactivity among them has been demonstrated, which may explain (together with profilin) the frequency of individuals sensitized to vegetable foods in the Mediterranean area.     

Allergie à lˈarachide

Peanut allergy, which is frequent in the United States and was much less so in Europe up to the mid-eighties, has become a major problem in many industrialized countries. Peanut consumption is high in Eastern Europe, the United Kingdom, The Netherlands, Germany and France. The frequency of peanut allergy is between 0.5 and 0.7% in the general population. Two million Americans are now thought to be affected. In France peanuts are one of the most frequent allergens, lying second (27.4%) to egg in food allergies in children, and holding first place in food allergies in children aged over 3 years. Sensitization occurs through ingestion, contact even if indirect, and inhalation. The symptoms, which affect the skin and the respiratory or gastrointestinal tract, appear a few minutes to a few hours after exposure. Serious reactions (anaphylactic shock, life-threatening reactions, sudden death) have been described. Asthma has a significantly higher association with peanut allergy than with other allergies, taken overall. As with other food allergies, diagnosis is based on history, prick-tests, screening for specific serum IgE and food challenge whose modalities (labial and oral challenge) are debated. For the time being, elimination is the only form of treatment. The development of a modified allergen as immunogenic as possible but practically without allergenic effects should give immunotherapy new impetus. Patients with severe peanut allergy should carry a card or wear a distinctive bracelet indicating their condition as well as an emergency kit including in particular epinephrine.     

Update on the Diagnosis and Treatment of Shellfish Allergy

Shellfish allergy is a frequent, long-lasting, life-threatening disorder. As shellfish consumption increases, the number of allergic reactions to shellfish is expected to continue to rise as well. During the past decade, much has been learned about the allergens involved in shellfish allergy. Potential cross-reacting allergens between shellfish and other arthropods have been identified. As our knowledge of shellfish allergen improves, we will be able to develop more accurate methods of diagnosing shellfish allergy. In addition, extensive research is currently under way for the development of safer, more effective methods of managing shellfish hypersensitivity.     

LTP allergy/sensitization in a pediatric population

Plant lipid transfer proteins (LTPs) are widespread plant food allergens, highly resistant to food processing and to the gastrointestinal environment, which have been described as the most common food allergens in the Mediterranean area. LTP allergy is widely described in adults, but it represents an emerging allergen also in the pediatric population. Little is known about the real prevalence and the clinical features of this allergy in children and it still often remains underdiagnosed in these patients.An early identification and a deeper knowledge of this allergy in childhood can avoid severe systemic reactions and improve the child's quality of life. Pediatricians should always consider the possibility of LTP involvement in cases of plant-derived food allergy.     

What are the links between food allergy and atopy ?

Food allergy and atopy are closely linked. In children, food allergy is often the first clinical manifestation of atopy and involved in flares of atopic dermatitis. It is usually disappearing with ageing except for some particular allergens. Asthma and/or allergic rhinitis might develop later particularly if there are some risk factors as familial history of atopy or sensitization to aeroallergens. However some food allergies as allergy to peanut or tree nuts may persist in adulthood sometimes inducing severe clinical manifestations especially in asthmatic patients. In adult, food allergy is mostly associated with oral syndrome linked to cross reactivity between pollen and raw food (fruits or vegetables). Systemic manifestations are more frequent in patients living in the Mediterranean area in relation to direct sensitization (without pollen allergy) to lipid transfer proteins that are particularly resistant.     

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.     

Food Allergy and Atopic Dermatitis: How Are They Connected?

Food allergy predominantly affects children rather than adults with atopic dermatitis (AD). Early food sensitization has been found to be significantly associated with AD. Three different patterns of clinical reactions to food allergens in AD patients have been identified: 1) immediate-type symptoms, 2) isolated eczematous late-type reactions, and 3) combined reactions. Whereas in children, allergens from cow’s milk, hen’s egg, soy, wheat, fish, peanut, or tree nuts are primarily responsible for allergic reactions, birch pollen–related food allergens seem to play a major role in adolescent and adults with AD in Central and Northern Europe. Defects in the epidermal barrier function seem to facilitate the development of sensitization to allergens following epicutaneous exposure. The relevance of defects in the gut barrier as well as genetic characteristics associated with an increased risk of food allergy remain to be further investigated. Many studies focus on sufficient strategies of prevention, which actually include breastfeeding or feeding with hydrolyzed formula during the first 4 months of life.     

Particularités de l'allergie alimentaire au porc

Food allergy to pork is rare. Here we report 13 cases, due mostly to pork kidney. The reactions can be severe, and cross reactions with other animal food for animal allergens are frequent. Better knowledge of the responsible allergens is necessary to be able to identify patients at risk.     

Gastrointestinal food hypersensitivity: Symptoms, diagnosis and provocation tests.

As many as 25% of the general population in Western countries believe that they suffer from adverse reactions to food. However, the actual prevalence of food allergy is much lower. Food-induced allergic reactions cause a variety of symptoms including cutaneous, gastrointestinal and respiratory tract. Food allergy might be caused by IgE-mediated, mixed (IgE and/or non-IgE) or non-IgE-mediated (cellular) mechanisms. The clinical diagnosis is based on a careful history, laboratory findings (total and specific IgE), skin prick test, elimination diet and food challenges. New intestinal provocation tests have also been applied to pick up the allergic response of the duodenal mucosa by endosonography and external ultrasound. The management of food allergy continues to be a strict avoidance of the offending food item.     

The "egg-egg" syndrome: occupational respiratory allergy to airborne egg proteins with consecutive ingestive egg allergy in the bakery and confectionery industry.

Allergies to various inhalative allergens are a serious problem in the bakery and confectionery industry. Sensitization to wheat flour and enzymes such as alpha-amylase are a frequent cause of occupational asthma. Airborne egg allergens have been reported as another cause of respiratory allergy. We examined bakery and confectionery workers with respiratory symptoms due to egg aerosols. Skin tests (SPT), scratch tests (ST), nasal provocation tests (NPT) and serological examinations (IgE) were performed. Lung function was assessed by spirometry, and continuous registration of aerosols and particulates as well as gravimetric sampling was done at the workplace. Four bakery and two confectionery workers intensively exposed to airborne egg proteins suffered from conjunctivitis and rhinitis, four also from asthma. Subsequently, three of these four workers reported symptoms after ingestion of food that contained egg. SPT with commercial egg white and egg yolk extracts were negative in four cases. Only two employees had clearly positive SPT to commercial egg allergens and reacted also to wheat flour extracts. Scratch tests with native egg proteins were positive in four employees. Specific IgE to egg white and egg yolk were positive (CAP > or = 2) in three and in four cases, respectively, whereas they were negative in two cases. Elevated levels of specific IgE to lysozyme were detected in four employees. Two workers were sensitized to lysozyme but not to other egg proteins. The clinical relevance of egg sensitization was confirmed by continuous air sampling and by correlating the onset of the respiratory symptoms which were reflected by a significant decline (> or = 30%) of the forced one second capacity (FEV1) in two workers. Sieving of egg white powder and an inadequate spray station for liquid eggs were identified as sources of excessive allergen exposure. Bakery and confectionery workers exposed to airborne egg proteins are at risk of developing occupational asthma and subsequent nutritive egg allergy. To our knowledge, these are the first cases of inhalative egg allergy and subsequent nutritive egg allergy reported in the literature, which we refer to as the "egg-egg syndrome" in analogy to the already known "bird-egg" and "egg-bird" syndromes.     

Meeting the nutritional needs of the low-birth-weight infant

Approximately 5% of young children and 3-4% of adults exhibit adverse immune responses to foods in westernized countries, with a tendency to increase. The pathophysiology of food allergy (FA) relies on immune reactions triggered by epitopes, i.e. small amino-acid sequences able to bind to antibodies or cells. Some food allergens share specific physicochemical characteristics that allow them to resist digestion, thus enhancing allergenicity. These allergens encounter specialized dendritic cell populations in the gut, which leads to T-cell priming. In case of IgE-mediated allergy, this process triggers the production of allergen-specific IgE by B cells. Tissue-resident reactive cells, including mast cells, then bind IgE, and allergic reactions are elicited when these cells, with adjacent IgE molecules bound to their surface, are re-exposed to allergen. Allergic reactions occurring in the absence of detectable IgE are labeled non-IgE mediated. The abrogation of oral tolerance which leads to FA is likely favored by genetic disposition and environmental factors (e.g. increased hygiene or enhanced allergenicity of some foods). For an accurate diagnosis, complete medical history, laboratory tests and, in most cases, an oral food challenge are needed. Noticeably, the detection of food-specific IgE (sensitization) does not necessarily indicate clinical allergy. Novel diagnostic methods currently under study focus on the immune responses to specific food proteins or epitopes of specific proteins. Food-induced allergic reactions represent a large array of symptoms involving the skin and gastrointestinal and respiratory systems. They can be attributed to IgE-mediated and non-IgE-mediated (cellular) mechanisms and thus differ in their nature, severity and outcome. Outcome also differs according to allergens.     

Allergies associated with both food and pollen

Recent progress in understanding structural relationships between allergens has allowed their classification into molecular families. Proteins belonging to a molecular family often show some degree of IgE cross-reactivity. These cross-reactions can lead to a clinical association like birch-apple syndrome whose basis is a sensitization to a PR-10 protein (birch pollen Bet v 1) and then oral symptoms in contact to apple Mal d 1, another PR-10 family member. Food allergens implicated into pollen-food allergy syndromes differ from those linked to crustacea or milk cross-allergies: they seem unable to sensitize the patient through oral route. As a result, they most often induce weaker clinical reactions than complete allergens like those present in shrimp or cow milk. Numerous molecular families have been isolated from pollens. PR-10 and profilins have a well established role in inducing clinical reactions to food like fruits and vegetables. Some molecular families need more studies to delineate their true impact on pollen-driven food reactions: polygalacturonases, pectate lyases, isoflavone reductases, thaumatin-like, cyclophilins.... Others are found in pollen but not in eaten products: 2-EF-hand calcium binding proteins, beta expansins,... Lipid transfer proteins (LTP) are widespread plant food allergens (e.g. in peach): these proteins seem able to directly sensitize the patient through oral route. But recent data have suggested a possible additional effect of some LTP present in pollens (mugwort, olive, pellitory).     

Wheat flour allergy: an entire diagnostic tool for complex allergy

Wheat proteins are involved in respiratory allergy, contact allergy and food allergy. Wheat allergens involve in these pathologies are well-known. However, establishment of wheat allergy diagnostic can be sometimes difficult on account of the complex allergenic composition of skin prick test (SPT) solutions of wheat flour. Therefore, we have studied specific IgE reactivity from patient sera with wheat food allergy, and characterized allergenic composition of wheat SPT solutions by specific antibodies directed to wheat allergens. The results showed that 20 of the 25 sera analyzed contained specific IgE to at least one wheat protein fraction. Among positive sera, 75% have specific IgE to water/salt soluble fraction, 85% to native gluten fractions and 65% to wheat isolate fraction. The results showed also that SPT solutions of wheat flour contained major food allergens from each allergenic fraction. These results highlighted the importance of using fractions, which constitute the whole wheat allergenic pattern, during specific IgE reactivity analyses. Moreover, we have observed that wheat isolate extract (results of food industrial process) contained not only modified allergens (neo-allergens) involve of specific food allergy to wheat isolate but also some native allergens involve in wheat food allergy. Thus, these results showed the importance to use, for wheat in vivo diagnosis together wheat SPT solutions (gluten extract and wheat isolate) in order to differentiate wheat food allergy to specific wheat isolate allergy.     

Latex allergy: Review of recent advances

Latex allergy is an IgE-dependent immediate hypersensitivity reaction to latex proteins. Risk factors for latex allergy are contact with latex products and atopy. Children who undergo multiple surgical procedures and healthcare workers are the major groups at risk. Powdered latex gloves are an important source of sensitization. Preventive measures are leading to reduction in latex sensitization and allergic reactions. The prevalence of latex allergy in the general population may be as low as 0.1%, whereas the frequency of latex sensitization is reported to be 7%; this may be due to cross-reacting antipollen IgE. The most important latex allergens have been purified, and some have been cloned and sequenced. Many latex-allergic patients are also allergic to common plant-derived aeroallergens and foods. The structural and biologic relationships among plant-derived food allergens, including latex, explain these clinically important cross-reactions.     

Food allergy: a challenge for the clinician

Adverse reactions to food resulting in gastrointestinal symptoms and due to immunologic reactions (allergy) are discussed: their pathogenesis, the prevalence of food allergens and the clinical digestive expressions of food allergy in children and adults are reviewed. In IgE-mediated food allergy, the usefulness of the biological available tests is considered, mainly CAP tests, for proceeding to the diagnosis and the monitoring of the allergic disease. Finally, the best actual diagnostic tools in food allergy are considered (clinical history, skin tests, biological tests and food oral challenges), with their limitations and indications.     

Allergic reactions to foods by inhalation

Although allergic reactions to foods occur most commonly after ingestion, inhalation of foods can also be an underlying cause of these reactions. For example, published reports have highlighted the inhalation of allergens from fish, shellfish, seeds, soybeans, cereal grains, hen’s egg, cow’s milk, and many other foods in allergic reactions. Symptoms have typically included respiratory manifestations such as rhinoconjunctivitis, coughing, wheezing, dyspnea, and asthma. In some cases, anaphylaxis has been observed. In addition, there have been many investigations of occupational asthma following the inhalation of relevant food allergens. This report reviews the current literature focusing on allergic reactions to foods by inhalation.