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Celery allergy confirmed by double-blind, placebo-controlled food challenge: A clinical study in 32 subjects with a history of adverse reactions to celery root
Abstract
Celery root is a frequent cause of food allergy in pollen-sensitized patients. Because of problems in blinding challenges with fresh vegetables and the risk of anaphylactic reactions, no double-blind, placebo-controlled, food challenges (DBPCFCs) with celery have been published so far.
The aim of the study was to confirm the clinical relevance of celery as a food allergen by DBPCFCs and to evaluate current diagnostic procedures in patients with true allergy.
DBPCFCs were performed in 32 patients with a history of an allergic reaction to celery. The patients underwent skin prick tests (SPTs) with celery extracts, crude celery, and different pollen extracts. Specific IgE for celery was determined by using the CAP method.
Twenty-two of 32 patients had a positive DBPCFC result. Two patients reacted to placebo, and 8 patients did not respond to the challenge. Of the nonresponders, 4 reacted to an open provocation with celery. The sensitivity of CAP determination for specific IgE (> or =0.7 kU/L) to celery in patients with a positive DBPCFC result was 73%, 48% to 86% for SPTs (> or =3 mm) with commercial extracts, and 96% for prick-to-prick tests with crude celery. The positive predictive value of the SPT and CAP tests was between 87% and 96%, whereas the specificity and negative predictive values were poor.
This study confirms the importance of celery as a food allergen for use in DBPCFCs. The SPT and CAP methods proved to be reliable for the diagnosis of a relevant allergy to celery in regard to sensitivity and positive predictive value but not to specificity and negative predictive value.
... Aspekte der Eignung von Nahrungsmitteln zur Nativtestung sind in der Leitlinie zur Hauttestung mit Nahrungsmittelallergenen genauer beschrieben [21]. Limitationen des nativen Prick-zu-Prick-Tests sind die geringe Spezi tät aufgrund möglicher irritativer Komponenten im Nahrungsmittel, die falsch-positive Reaktionen auslösen können, sowie ob das entsprechende Nahrungsmittel in frischer Form überhaupt verfügbar ist [26,27]. Die Testung mit nativem Material beinhaltet die Anwendung nichtstandardisierter Allergenextrakte bzw. ...
... In der Regel sind die birkenpollenassoziierten Nahrungsmittelallergien durch das Au reten vorwiegend oropharyngealer Symptome gekennzeichnet. Jedoch gibt es in der Literatur zahlreiche Fallberichte, bei denen schwere Reaktionen aufgrund einer Bet v 1-Kreuzreaktivität aufgetreten sind [15,26,27,55,56]. Häu ge und typische Nahrungsmittel, die schwere Reaktionen im Rahmen der Kreuzreaktivität gegenüber Bet v 1 auslösen, sind Haselnuss, Karotte, Soja und auch seltene Vertreter wie die Sharon-Frucht. ...
... -Symptomarme Intervalle sind zu bevorzugen.-Die Zubereitung des nativen Testmaterials sollte aufgrund der Instabilität bestimmter Allergene frisch erfolgen[26,27,43]. -Je nach Stärke der vermuteten Reaktion kann primär eine Schleimhautprovokation und anschließend die systemische Provokation in ansteigender Menge[16,26,44] erfolgen (Tabelle 6). ...
In adults, the majority of IgE-mediated food aller gies is caused by cross-reacting allergen molecular structures that are present in inhalant as well as food allergens. On the one hand, synthesis of IgE stimulated by a cross-reactive allergen in pollen can result in a diverse pattern of sensitizations against various foods. On the other hand, even anaphylactic reactions may occur after first consumption of a food containing a cross-reactive allergen.
In clinical practice, it is not sufficient to detect cross-reactivities by immunologic assays. Clinically relevant sensitizations have to be distinguished from clinically irrelevant IgE responses. Hence, in cases of unclear history oral challenge tests are nec essary.
A few open studies have demonstrated the therapeutic potential in pollen-related food allergy: in at least 50% of the cases, tree pollen immunotherapy led to an improvement of associated food allergies. However, these results have to be con firmed in placebo-controlled studies.
As we are facing an increase of pollen allergies, a shift in sensitization patterns and changes in nutri tional habits, the occurrence of new, so far unknown cross-reactions is expected.
... Furthermore, fruits such as peaches, apples, pears, kiwi, melons, and nuts are known to cause oral allergy syndrome in patients with an allergy to olive pollen [52]. In the case of Artemisia vulgaris pollen (the Art v 1 glycoprotein is recognized as the dominant allergen), the cross-reactions of its allergens with food are rare and insufficiently confirmed, but are known to lead to more severe anaphylactic reactions [153,160]. ...
... In most pollen-related foods, potential allergenic structures are thermally labile, and the vast majority of potentially allergic people tolerate these foods after heating by boiling, baking, or cooking [52]. Some cases of deviation from this rule have been observed in roasted hazelnuts and cooked celery which may cause allergic symptoms in highly sensitive patients due to the residual and preserved small amounts of pollen-related allergens [52,163], such as lipid transfer proteins in hazelnut Cor a 8 (heat resistant below 100 • C) or celery Api g 2, which show stability during heat treatment [154,160,164,165]. In the studies of Hansen et al. [166] and Worm et al. [163] the complete tolerance to roasted hazelnut was confirmed in 70.6% and 15% of cases, respectively, among the subjects with a confirmed allergy to raw hazelnuts. ...
Pollen is recognized as an excellent dietary supplement for human nutrition, which is why it can be found in different forms on the market (granules, capsules, tablets, pellets, and powders). But, the digestibility of pollen's nutrients is strongly affected by the presence of a pollen shell, which can decrease the bioavailability of nutrients by 50% and more. Since consumers have become more aware of the benefits of a healthy diet and the necessity to improve pollen digestibility, different pollen-based functional food products have been developed and extensive studies were done to estimate the beneficial effects of pollen-based feed on animal growth, health, and rigor mortise stage. Considering the positive effects of pollen nutrients and phytometabolites on human and animal health, the aim of this paper was to give an overview of recent achievements in the application of pollen in the formulation of functional food and animal diets. Special attention was paid to the effects of pollen's addition on the nutritional, functional, techno-functional, and sensory properties of the new formulated food products. Anti-nutritional properties of pollen were also discussed. This review points out the benefits of pollen addition to food and feed and the possible directions in the further development of functional food and feed for the wellbeing of everyone.
... Cross-reactions are frequently observed between pollens and certain foods, especially fruits and vegetables 68,69 . This is the oral allergy syndrome, which typically involves mild reactions as previously mentioned. ...
... This is the oral allergy syndrome, which typically involves mild reactions as previously mentioned. Examples include cross-reactions between birch pollen and apples, ragweed pollen and melons, and mugwort pollen and celery [68][69][70] . Cross-reactions have also been noted between latex allergies, a common problem among health-care workers, and certain foods including bananas, kiwis, avocados, and chestnuts. ...
The immune system protects our body against pathogens and other foreign substances by producing a kind of glycoprotein known as immunoglobulin or antibodies from plasma cells or B-cells. Surveys show that about one-third of all adults believe they have food allergies. About 4-8% percent of young children are diagnosed with food allergies, most of which are evident in the first years of life and are often outgrown. A food allergy is any adverse reaction to an otherwise harmless food or food component that involves the body’s immune system. In others words, a food allergy is an immune system response to a food that the body mistakenly believes is harmful. Components of a food that trigger the immune system are called food allergens. Cows’ milk allergy appears to be among the more prevalent food allergies in infants. Eggs and peanuts are also common allergenic foods for infants, along with soybeans, tree nuts, fish, and wheat. Seafood allergies, especially to crustaceans (shrimp, crab, lobster) are also rather common among adults. The present review provides brief information about food allergy and allergic reactions, their types, symptoms and approaches for reduction.
... Moreover, even with well prepared extracts, false positive SPT or elevated food specific IgE do occur due to clinically silent or insignificant sensitisation or cross-reaction, respectively, which explains the overall observed low specificity and low positive predictive value of SPT or in vitro testing for specific IgE in food allergy.These are often below 50%, particularly in children with atopic dermatitis [24][25][26]. In adults, however, this figure is higher, at about 80% [22,23,[27][28][29]. Thus, positive diagnostic tests indicate the presence of food specific IgE antibodies, but they do not establish the diagnosis of food allergy and negative diagnostic tests might be the consequence of the unavailability of standardised meat extracts. ...
... Die klinische Symptomatik reduziert sich in der Regel auf ein OAS, welches allerdings manchmal schwer ist und zu relevanter Atemnot führen kann, vor allem, wenn es zu einer Larynxschwellung kommt. Systemische Reaktionen auf kreuzreaktive PR10-Proteine sind beschrieben für Soja (Gly m 4) [28,29], Karotte (Dau c 1) [30], Haselnuss (Cor a 1), Sellerie (Api g 1) [31,32], Sharonfruit (Kaki, [33]) und Jackfruit [34]. ...
... 26 87% of celery allergic people, 52% of carrot allergic people, and 26% of caraway seed allergic people also show hypersensitivity towards mugwort leading to the concept of the celery-carrot-mugwort-birch-spice syndrome. 27,28 Mugwort shares common epitopes with other tree pollens like birch, olive, Italian funeral cypress, and pine. 29 Cross-reactivity is also observed between the alder tree and mugwort due to the presence of calcium-binding proteins in either. ...
Pollens are typically the primary reason for seasonal hypersensitivity caused in many people that are released by a hundred different species of plants for fertilization. Not all pollens are the same or have the same effect on human beings, there are those worse than others. The human body works out on a defence mechanism by creating certain reactions against those offensive pollens as a response by the immune system. The allergic reactions include sneezing, coughing, wheezing, itching, red-watery swelled eyes, runny nose, inflammation in the nasal passage frequently leading to rhinitis, asthma, skin irritation, and other respiratory disorders. This study is intended to acquire knowledge about a few plants with high allergenic properties along with their major allergens. It is evident that the pollination of the plants varies from season to season as it depends on various factors such as species, weather, and geographical location. Understanding these high allergenic plants with respect to their varying factors and cross-reacting properties is the purpose of this study. It is an effort to obtain deeper insights into these common pollen offenders.
... Clinical symptoms are usually reduced to an oral allergy syndrome, which, however, is sometimes severe and may lead to relevant respiratory distress, especially if laryngeal swelling occurs. Systemic reactions to crossreactive PR10 proteins have been described for soy (Gly m 4) [28,29], carrot (Dau c 1) [30], hazelnut (Cor a 1), celery (Api g 1) [31,32], Sharon fruit [33], and jackfruit [34]. ...
Background
Food-associated complaints in the gastrointestinal tract can be signs of an intolerance of different etiology, which is reported by almost a quarter of the population. Due to the unspecific symptoms, a whole range of different triggers and immune reactions can be considered for the differential diagnosis, which cannot always be determined unambiguously and quickly.Differentiation and diagnosis of disease entityThe time course in connection with the clinical picture already allows a rough estimation of the underlying pathomechanism and points the diagnostic way. Thus, immune-mediated clinical pictures such as allergy must be distinguished from nonimmune-mediated intolerances. An allergic reaction can be IgE-mediated or cellularly induced. Secondary food allergies are triggered by other allergens than primary allergies, differ in their sensitization routes and course of disease. Non-immunological intolerance reactions also play a not insignificant role, including carbohydrate utilization disorders and histamine intolerance in addition to toxic reactions. Often difficult to identify are also those food components which trigger a nonspecific mast cell activation. Due to their particular clinical relevance, wheat intolerances of different pathogenesis are also discussed. As a consequence of their complexity with regards to disease-causing proteins, target organ manifestations, pathomechanisms and diagnostic clarification, these require a particularly differentiated approach.PurposeThis review article presents the current recommendations regarding the diagnosis of food intolerance and food allergy, with a separate focus on the specifics in the interpretation of different tests including IgE diagnostics.
... In dieser Dekade setzte sich die "doubleblind, placebo controlled food challenge" (DBPCFC) durch als die einzige valide Methode (golden standard), um eine allergische Reaktion auf Nahrungsmittel sicher zu diagnostizieren [54,55]. Auch auf der Allergiestation in Zürich wurde diese Methode durch B. Ballmer-Weber und Mitarbeiter für eine Anzahl wichtiger Nahrungsmittel (Sellerie, Weizen, Milch, Kirschen, Haselnuss, usw.) eingeführt [56]. ...
In the 1960s, there were few scientific publications on the subject of “food aller-gies”; for the German-speaking allergist, the manuals edited by Karl Hansen and by Karl Hansen and Max Werner were the daily used “bible”. Few foods were considered as aller-gens, the clinical picture of “oral allergy syn-drome” (OAS) was not yet known, and the concept of pollen-associated food allergies was not yet established. Diagnostic methods were mainly based on a subtly collected pa-tient history and on the performance of ex-tensive skin tests according to the prick and intracutaneous method (“large antigen test” according to Hansen). Especially in cases of occupational allergies to dusts, the rubbing test described in Bad Lippspringe in 1961 was used. The pulse test according to Coca, the leucopenic index according to Vaughan, and the platelet fall test according to Storck
(19) (PDF) Sechs Dekaden Nahrungsmittelallergie. Available from: https://www.researchgate.net/publication/353798624_Sechs_Dekaden_Nahrungsmittelallergie [accessed Aug 20 2021].
... The most frequent OAS occurs in Bet v 1-sensitized patients when eating fruits from the Rosaceae family, mainly apple. Apple OAS depends on the molecular homology between Bet v 1 and the Bet v 1-homologous Mal d 1, the major allergen of apple belonging to PR-10 family (Ballmer-Weber et al., 2000;Ballmer-Weber & Hoffmann-Sommergruber, 2011;Boyano-Martínez et al., 2013;Fernández-Rivas et al., 2006). According to our results, patients suffering from the sensitization to Phl p1, Phl p 2, Phl p 4, Phl p 5, Phl p 6 and Phl p 7 suffer significantly more often from food reaction to peanuts, the sensitization to Phl p 11 and Phl p 12 is in significant relation to food reaction to peach. ...
To evaluate the relation between the sensitization to molecular components of inhalant allergens and the occurrence of food reactions in atopic dermatitis patients. Another aim is to evaluate the semi-quantification results of the ISAC Multiplex testing to reveal the relevance of the leading allergens. The complete dermatological and allergological examination including the examination of the sensitization to molecular components with Multiplex ISAC testing was performed. The food reactions to examined food allergens were confirmed in the open exposure test (history). Altogether 100 atopic dermatitis patients were examined – 48 men, 52 women, the average age 40.9 years. The leading molecular components are cysteine protease (Der f 1, Der p 1), NPC2 protease (Der f 2, Der p 2), Acidic glycoprotein (Alt a 1), PR 10 proteins (Bet v 1, Mal d 1, Aln g 1 and Cor 1.04), lipocalins (Can f 1, Fel d 4, Mus m 1, Equ c 1), uteroglobulin (Fel d 1), Kallikrein (Can f 5) and molecular components of Timothy and Bermuda grass (glycoprotein). The significantly higher occurrence of sensitization to molecular components Aln g 1, Bet v 1, Phl p 1, 2, 4, 5, 6, 11 was confirmed in patients suffering from reactions to peanuts, hazelnuts, celery, apple and peach.
... The symptoms induced by food Bet v 1-like proteins are not usually severe, although some anaphylactic reactions to soy [81], celery (Api g 1), carrot (Dau c 1) [82,83], jackfruit and sharon fruit [84,85] or to different mixed vegetables have been described [86]. Actually, in most cases it was not possible to discriminate whether the reaction was caused by Bet v 1-like proteins or by other allergens. ...
Oral allergy syndrome (OAS) is one of the most common IgE-mediated allergic reactions. It is characterized by a number of symptoms induced by the exposure of the oral and pharyngeal mucosa to allergenic proteins belonging to class 1 or to class 2 food allergens. OAS occurring when patients sensitized to pollens are exposed to some fresh plant foods has been called pollen food allergy syndrome (PFAS). In the wake of PFAS, several different associations of allergenic sources have been progressively proposed and called syndromes. Molecular allergology has shown that these associations are based on IgE co-recognition taking place between homologous allergens present in different allergenic sources. In addition, the molecular approach reveals that some allergens involved in OAS are also responsible for systemic reactions, as in the case of some food Bet v 1-related proteins, lipid transfer proteins and gibberellin regulated proteins. Therefore, in the presence of a convincing history of OAS, it becomes crucial to perform a patient's tailored molecule-based diagnosis in order to identify the individual IgE sensitization profile. This information allows the prediction of possible cross-reactions with homologous molecules contained in other sources. In addition, it allows the assessment of the risk of developing more severe symptoms on the basis of the features of the allergenic proteins to which the patient is sensitized. In this context, we aimed to provide an overview of the features of relevant plant allergenic molecules and their involvement in the clinical onset of OAS. The value of a personalized molecule-based approach to OAS diagnosis is also analyzed and discussed.
... Additionally, positive reactions to placebo are not uncommon and can have a varied clinical presentation. In our experience, 12.7% of participants had positive placebo challenges, which is consistent with the published literature (38)(39)(40)(41)(42)(43)(44). In light of these significant burdens, there is a great need for a reliable method of diagnosing food allergies without food challenges, in addition to the ability to stratify participants according to potential risk in scenarios where a food challenge cannot be avoided. ...
Background: Double-blind placebo-controlled food challenges (DBPCFCs) remain the gold standard for the diagnosis of food allergy; however, challenges require significant time and resources and place the patient at an increased risk for severe allergic adverse events. There have been continued efforts to identify alternative diagnostic methods to replace or minimize the need for oral food challenges (OFCs) in the diagnosis of food allergy.
Methods: Data was extracted for all IRB-approved, Stanford-initiated clinical protocols involving standardized screening OFCs to a cumulative dose of 500 mg protein to any of 11 food allergens in participants with elevated skin prick test (SPT) and/or specific IgE (sIgE) values to the challenged food across 7 sites. Baseline population characteristics, biomarkers, and challenge outcomes were analyzed to develop diagnostic criteria predictive of positive OFCs across multiple allergens in our multi-allergic cohorts.
Results: A total of 1247 OFCs completed by 427 participants were analyzed in this cohort. Eighty-five percent of all OFCs had positive challenges. A history of atopic dermatitis and multiple food allergies were significantly associated with a higher risk of positive OFCs. The majority of food-specific SPT, sIgE, and sIgE/total IgE (tIgE) thresholds calculated from cumulative tolerated dose (CTD)-dependent receiver operator curves (ROC) had high discrimination of OFC outcome (area under the curves > 0.75). Participants with values above the thresholds were more likely to have positive challenges.
Conclusions: This is the first study, to our knowledge, to not only adjust for tolerated allergen dose in predicting OFC outcome, but to also use this method to establish biomarker thresholds. The presented findings suggest that readily obtainable biomarker values and patient demographics may be of use in the prediction of OFC outcome and food allergy. In the subset of patients with SPT or sIgE values above the thresholds, values appear highly predictive of a positive OFC and true food allergy. While these values are relatively high, they may serve as an appropriate substitute for food challenges in clinical and research settings.
... The symptoms that develop after the ingestion of plant foods are usually mild, as the proteins responsible are thermolabile. Nevertheless, systemic reactions have been described by some PR-10 allergens such as Gly m 4 from soy [9] or Api g 1 [10] from celeriac. In southern Europe, on the other hand, allergic reactions to foods derived from plants are usually associated with systemic reactions due to a primary sensitization to LTPs, though thaumatin-like proteins (TLPs) have been also described as a cause of severe reaction to fruits in Spain [11]. ...
Purpose of Review
To critically examine evidence suggesting that food allergy induced by lipid transfer proteins (LTPs) follows a geographic pattern.
Recent Findings
LTP syndrome remains most common in the Mediterranean basin, with a clear gradient seen in prevalence of LTP sensitization between northern and southern Europe. We hypothesize that high levels of birch pollen seem to protect against LTP allergy, as these higher levels correlate with a lower prevalence of LTP hypersensitivity. Nevertheless, LTP food allergy cases still appear in areas having a high environmental level of birch pollen.
Summary
Food allergy caused by LTP may be related to (1) primary sensitization to a food LTP allergen in the absence of pollinosis, (2) primary sensitization to LTP from a pollen source, and (3) co-sensitization to LTP from pollen and food.
... Celery is recognized as a healthy vegetable because of its abundant nutrients over the world, whereas celery is also one of the common plant food sources that cause allergic reactions in central European human (30)(31)(32). The allergenic reaction to celery induces many symptoms such as human oral allergy, severe cases exhibited life-threatening anaphylactic reactions (33,34). So far, several allergens were identified from celery, including Api g 1 (35), Api g 2 (36), Api g 4 (37), Api g 5 (38) and Api g 6 (39). ...
Celery (Apium graveolens L.) is a plant belonging to the Apiaceae family, and a popular vegetable worldwide because of its abundant nutrients and various medical functions. Although extensive genetic and molecular biological studies have been conducted on celery, its genomic data remain unclear. Given the significance of celery and the growing demand for its genomic data, the whole genome of ‘Q2-JN11’ celery (a highly inbred line obtained by artificial selfing of ‘Jinnan Shiqin’) was sequenced using HiSeq 2000 sequencing technology. For the convenience of researchers to study celery, an online database of the whole-genome sequences of celery, CeleryDB, was constructed. The sequences of the whole genome, nucleotide sequences of the predicted genes and amino acid sequences of the predicted proteins are available online on CeleryDB. Home, BLAST, Genome Browser, Transcription Factor and Download interfaces composed of the organizational structure of CeleryDB. Users can search the celery genomic data by using two user-friendly query tools: basic local alignment search tool and Genome Browser. In the future, CeleryDB will be constantly updated to satisfy the needs of celery researchers worldwide.
Database URL: http://apiaceae.njau.edu.cn/celerydb
... Cross-reactivity between mugwort and mustard has also been demonstrated, and accordingly, celery-birch-mugwort-spice syndrome has been used to describe these cross-reactivities (12). Celery root (which is mainly consumed in Switzerland) has been associated with systemic symptoms in the "mugwort-celery-spice syndrome" (13), whereas celery stick is more often associated with OAS in birch pollen-allergic subjects (14). Melon-induced OAS in ragweed-allergic subjects has been observed to be associated with profilin sensitization (15). ...
Plant allergens, being one of the most widespread allergenic substances, are hard to avoid. Hence, their identification and characterization are of prime importance for the diagnosis and treatment of food allergy. The reported allergies to fruits mainly evoke oral allergy syndrome caused by the presence of cross-reactive IgE to certain pollens and thus, allergy to fruits has also been linked to particular pollens. Many fruit allergies are being studied for their causative allergens, and are being characterized. Some tropical or exotic fruits are responsible for region-specific allergies for which only limited information is available, and generally lack allergen characterization. From a survey of the literature on fruit allergy, it is clear that some common fruits (apple, peach, musk melon, kiwi fruit, cherry, grape, strawberry, banana, custard apple, mango and pomegranate) and their allergens appear to be at the center of current research on food allergy. The present review focuses on common fruits reported as allergenic and their identified allergens; a brief description of allergens from six rare/tropical fruits is also covered.
... Celery represents an important plant allergen source, causing reactions from mild oral allergy and skin symptoms to more severe respiratory symptoms and life-threatening anaphylactic reactions (Wuthrich and Dietschi, 1985;Ballmer-Weber et al., 2000). Due to phototoxic reactions, skin reactions can occur when handling the leaves in light. ...
Description of the book.
Medicinal herbs are rich in vitamins, minerals and antioxidants, and are able to synthesize secondary metabolites with disease preventive properties. It is due to these qualities that herbs have been used throughout history for flavouring and in food, medicine and perfumery preparations. They are also often considered to be safe alternatives to modern medicines because of their healing properties. Though interest in medicinal and aromatic crops is growing worldwide, there is still little focus on the area of leafy medicinal herbs.
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Since the discovery of immunoglobulin E (IgE) as a mediator of allergic diseases in 1967, our knowledge about the immunological mechanisms of IgE‐mediated allergies has remarkably increased. In addition to understanding the immune response and clinical symptoms, allergy diagnosis and management depend strongly on the precise identification of the elicitors of the IgE‐mediated allergic reaction. In the past four decades, innovations in bioscience and technology have facilitated the identification and production of well‐defined, highly pure molecules for component‐resolved diagnosis (CRD), allowing a personalized diagnosis and management of the allergic disease for individual patients. The first edition of the “EAACI Molecular Allergology User's Guide” (MAUG) in 2016 rapidly became a key reference for clinicians, scientists, and interested readers with a background in allergology, immunology, biology, and medicine. Nevertheless, the field of molecular allergology is moving fast, and after 6 years, a new EAACI Taskforce was established to provide an updated document. The Molecular Allergology User's Guide 2.0 summarizes state‐of‐the‐art information on allergen molecules, their clinical relevance, and their application in diagnostic algorithms for clinical practice. It is designed for both, clinicians and scientists, guiding health care professionals through the overwhelming list of different allergen molecules available for testing. Further, it provides diagnostic algorithms on the clinical relevance of allergenic molecules and gives an overview of their biology, the basic mechanisms of test formats, and the application of tests to measure allergen exposure.
Objective. The aim of this study was to research a sIgE allergen profile of birch pollen and to evaluate a contribution of some homologous food allergens as well as latex allergen to the development of sensibility in allergic rhinitis (AR) / rhinoconjunctivitis patients, in focus of cross-reactivity and oral allergy syndrome.. Methods. Blood sera of 21 AR/rhinoconjunctivitis patients (at the age of 3 to 16) and 20 healthy persons without allergy symptoms were used. sIgE to birch pollen, soybean, latex, apple and celery as well as the total IgE levels were measured by the ImmunoCAP method (Phadia, Sweden) and the ELISA kits (Alkorbio, Russia). Results. We detected high total IgE levels, sIgE to allergens of birch pollen, apple, celery, as well as to recombinant allergens of birch Bet v 1, Bet v 2 and soybean - Gly m 4 in AR patients. Correlation analysis of IgE humoral response to homologous proteins showed the direct valid dependence between the sIgE levels to birch isoallergen Bet v 1 and soy isoallergen Gly m 4 (r=0,84; p
Vegetables provide important nutrients but can also induce allergic symptoms. Celery tuber allergy frequently occurs in Central European countries and can cause allergic reactions including fatal anaphylactic shocks. There is little information about allergen content in seeds. Therefore, we analyzed 2 patients with allergic reaction after remoulade sauce consumption who entered the clinic for a diagnostic work-up. The routine diagnostic included serum derived specific IgE testing by ImmunoCAP, ImmunoCAP ISAC, and skin prick tests (SPTs). Furthermore, protein extracts were prepared from both celery tuber and celery seeds and IgE binding capacity of these extracts was assessed by immunoblots, ELISA, and rat basophil leukemia (RBL) assay. We also determined role of cross-reactive carbohydrate determinants (CCDs) by IgE inhibition ELISA. Results revealed distinct protein patterns from celery tuber and seed extracts, suggesting differences in content and quantity of allergenic proteins. IgE antibodies from both sera bound to high molecular weight (HMW) proteins on immunoblots and caused high basophil response, which was also observed upon addition of glycosylated proteins as horseradish peroxidase and Api g 5, respectively. Our results indicate that it is worth considering CCDs from plant foods as a possible allergenic factor and their contribution to the mugwort-celery syndrome.
Aim: To evaluate the occurrence of food allergy to peach/apple/celery in atopic dermatitis patients and to analyse the sensitisation to molecular components.
Methods: The diagnosis of food allergy was confirmed according to the results of the challenge test/history and according to the examination of the sensitisation to molecular components with Multiplex ISAC testing.
Results and conclusion: Altogether 113 atopic dermatitis patients were examined – 54 men, 59 women, the average age 39.9 years. Allergy to apple was confirmed in 18 patients (15.9%), to peach in 17 patients (15.1%), to celery in 6 patients (5.3%). The sensitisation to Bet v 1 (Birch, PR 10 protein) was confirmed in 64 patients (56.7%) included in the study. From the whole number of patients with sensitisation to Bet v 1, we confirmed in 42.2% food allergy and in 48.4% food sensitisation to apple/peach/celery.
Background:
Previous studies demonstrated that birch pollen-related foods can cause late eczematous responses in birch pollen-sensitized patients with atopic dermatitis (AD). However, suitable markers to predict birch pollen-related food allergy in patients with AD are still lacking.
Objective:
We evaluated the correlation of the results from ImmunoCAP® fluorescence enzyme immunoassay (FEIA) singleplex and ImmunoCAP® immuno solid-phase allergen chip (ISAC) multiplex system in AD patients and investigated the diagnostic validity of allergen microarray analysis, measuring specific IgE (sIgE) with ImmunoCAP® ISAC to predict birch pollen-related food allergy in patients with AD.
Methods:
A total of 19 children and adults with AD, existing IgE-mediated birch pollen sensitization, and suspected birch pollen-related food allergy underwent a double-blind placebo-controlled food challenge (DBPCFC) in the clinical routine. Total and sIgE levels to birch pollen, Bet v 1, Bet v 2, and birch pollen-related foods (apple, carrot, celery, and hazelnut) were determined prior to the DBPCFC by ImmunoCAP®-FEIA. Additionally, allergen microarray ImmunoCAP® ISAC analysis was performed. Data were analyzed retrospectively.
Results:
Twelve out of 19 patients (63% responders) experienced an allergic reaction upon DBPCFC. Overall, 7 patients (37%) developed a significant deterioration of AD with a median increase of 12.4 points in the scoring of atopic dermatitis (SCORAD) index (range 10.0-15.7). Oral allergy syndrome was the predominant immediate-type symptom (n = 11/12 responders). There were no differences in sensitization frequencies regarding allergens of the pathogenesis-related protein family 10 between responders and non-responders. In all patients, correlation of IgE levels determined with ImmunoCAP® ISAC and ImmunoCAP®-FEIA, respectively, was significant with high correlation coefficients regarding birch pollen allergen extract, rBet v 1, and rBet v 2 (rs > 0.8, p < 0.001) and lower but also significant correlation coefficients regarding food allergens (rs < 0.8, p < 0.05-<0.001).
Conclusion:
ImmunoCAP® ISAC microarray allows displaying a differentiated sensitization profile in birch pollen-sensitized patients with AD. However, IgE-mediated sensitization against birch pollen-related allergens revealed by the allergen multiplex system does not predict late eczematous reactions upon DBPCFC with birch pollen-related foods.
Oleoresin is a mixture of volatile and nonvolatile components available in whole extract of natural herb or spice. It principally comprises essential oils and resin. Lemongrass oleoresins come from the Cymbopogon species, which grow in the tropical and subtropical regions of the world. Oleoresin of lemongrass is a dark green-colored viscous liquid having a characteristic lemon aroma and flavor and is mostly used as a flavoring ingredient. The lemon prefix in the lemongrass specifies the characteristic lemon-like odor, which is due to the availability of citral content (mixture of two isomeric aldehydes, geranial and neral). It has been utilized in synthesizing flavors, perfumes, cosmetics, detergents, and in the food and pharmaceutical industries. Different methods are used to extract the lemongrass essential oil, but steam distillation is the most suitable method as it doesn’t alter the quality of the obtained oil. The chemical composition of lemongrass oil varies depending on its extraction methods, genetic differences, harvest period, photoperiod, plant age, farming practices, and geographical origin. Lemongrass essential oil has shown several biological activities, including antimicrobial, antifungal, antiprotozoan, antioxidant, antidiarrheal, antimutagenic, antiinflammatory, antimalarial, antinociceptive, antihepatotoxic activities, etc. Lemongrass oil is a potent food preservative because of its extraordinary antifungal and antibacterial activities.
Food allergy is becoming a great problem in industrialized countries. Thus, there is the need for a robust understanding of all aspects characterizing IgE response to allergens. The epitope mapping of B-cell epitopes has the potential to become a fundamental tool for food allergy diagnosis and prognosis and to lead to a better understanding of the pathogenesis. Using this approach, we have worked on epitope mapping of the most important plant food allergens identified in the Mediterranean area. The final aim of this study is to define the immune response regarding B epitopes and its clinical relevance in LTP allergy. This chapter describes the protocol to produce microarrays using a library of overlapping peptides corresponding to the primary sequences of allergenic lipid transfer proteins.
While the intake of fruits and vegetables has been recommended for maintaining good health and preventing lifestyle-related diseases, in recent years, an increase in the prevalence of allergies to fruits and vegetables, e.g., pollen-associated food allergy syndrome (PFAS), has been reported. Meanwhile, fruit allergens causing severe anaphylaxis have been reported; new allergens have been discovered and their pathological mechanisms have been clarified. Most of the symptoms induced by fruits or vegetables are localized around the mouth and are self-limiting; however, systemic allergic symptoms such as anaphylactic shock, which are mainly caused by the specific characteristics of allergens such as resistance to heat and digestive enzymes, may develop in some cases. Recently, especially in Italy and Japan, gibberellin-regulated protein (GRP) has been identified as an allergen causing severe systemic peach allergy. Understanding allergens that are highly conserved across species (i.e., pan-allergens) is becoming increasingly important for diagnostics and research in food allergy.
Taken into account data from which is considered a product not safe, estimate the safe level of a contaminant on food, for example, always have many unavoidable uncertainties. It cannot be overemphasized enough, that this also happens as in any other human activity. In most cases, we hope, to define as clearly as possible the eventual risk associated with particular conditions of exposure to a given substance in food. There are numerous toxic compounds that reside naturally in certain foods that unable these to be consumed above certain limits or even are fully prohibited in some other countries. Chapter starts with a clear explanation of differences and relationships between food allergy and food poisoning, continued with main allergens in food and main toxics. Finally, authors summarize different origins of toxins and allergens (natural from foods, from additives, pollutants and food processing).
Pollen-food allergy syndrome (PFAS) is an immunoglobulin E-mediated immediate allergic reaction caused by cross-reactivity between pollen and the antigens of foods-such as fruits, vegetables, or nuts-in patients with pollen allergy. A 42.7% prevalence of PFAS in Korean pediatric patients with pollinosis was recently reported. PFAS is often called oral allergy syndrome because of mild symptoms such as itching, urticaria, and edema mainly in the lips, mouth, and pharynx that appear after food ingestion. However, reports of systemic reactions such as anaphylaxis have been increasing recently. This diversity in the degree of symptoms is related to the types of trigger foods and the characteristics of allergens, such as heat stability. When pediatric patients with pollen allergy are treated, attention should be paid to PFAS and an active effort should be made to diagnose it.
Food allergy and allergen management are important global public health issues. In 2011, the first iteration of our allergen threshold database (ATDB) was established based on individual NOAELs and LOAELs from oral food challenge in roughly 1750 allergic individuals. Population minimal eliciting dose (EDp) distributions based on this dataset were published for 11 allergenic foods in 2014. Systematic data collection has continued (2011–2018) and the dataset now contains over 3400 data points. The current study provides new and updated EDp values for 14 allergenic foods and incorporates a newly developed Stacked Model Averaging statistical method for interval-censored data. ED01 and ED05 values, the doses at which 1%, and respectively 5%, of the respective allergic population would be predicted to experience any objective allergic reaction were determined. The 14 allergenic foods were cashew, celery, egg, fish, hazelnut, lupine, milk, mustard, peanut, sesame, shrimp (for crustacean shellfish), soy, walnut, and wheat. Updated ED01 estimates ranged between 0.03 mg for walnut protein and 26.2 mg for shrimp protein. ED05 estimates ranged between 0.4 mg for mustard protein and 280 mg for shrimp protein. The ED01 and ED05 values presented here are valuable in the risk assessment and subsequent risk management of allergenic foods.
Most plants and plant products are innocuous, but a minority cause a variety of mild to severe adverse skin reactions that include urticaria, irritant contact dermatitis, allergic contact dermatitis, and phototoxic dermatitis. Although irritant contact dermatitis is the most common of these skin manifestations, this chapter focuses on plant-induced urticaria as well as effective treatments and preventive strategies.
Background:
Although epidemiologic data are scarce, there is no doubt that the increase in pollen allergies is going to be followed by an increase in the so-called pollen-related food allergies. The aim of this study was the evaluation of the food hypersensitivity reactions in atopic dermatitis patients and the relation to the sensitization to grass and trees.
Methods:
The complete dermatological and allergological examinations were performed in all included patients; the occurrence of food hypersensitivity reactions was recorded and the sensitization to inhalant allergens (grass and trees) was examined (skin prick test, and specific IgE). The statistical evaluation of the relation between the sensitization to these inhalant allergens and the occurrence of food hypersensitivity reactions was performed.
Results:
A total of 321 patients were included, with an average age of 26.7 years (±9.2 years) and with an average SCORAD of 33.2 (±13.3) points. The significant relation was recorded between the patients suffering from sensitization to grass and the reactions to peanuts, celery and walnuts; another significant relation was demonstrated between the patients suffering from sensitization to trees and reactions to apple, peanuts, and walnuts. In patients suffering from sensitization to grass and trees, the occurrence of food hypersensitivity reactions to tomatoes, kiwi, spices, oranges, capsicum, tangerines, and carrot was higher also, but the relation was not significant.
Conclusion:
The significant relation was found between the reactions to peanuts and walnuts and sensitization to grass and trees, another significant relation was found between the sensitization to grass and celery and between the sensitization to trees and apple.
Résumé
Par définition, le syndrome oral (SO) devrait correspondre à des symptômes qui restent limités à la cavité bucco-pharyngée. Les allergènes en cause (principalement PR10 et profilines) sont fragiles et facilement dénaturés par l’acidité gastrique. Toutefois, de nombreux cas de « syndrome oral aggravé », voire de véritables anaphylaxies, sont décrits avec ces allergènes. Les facteurs favorisants sont principalement l’effort physique, les infections, les antiinflammatoires (AINS) et les antiacides (IPP).
Background
Previous studies have indicated that in patients with atopic dermatitis (AD) and birch pollen allergy related foods are able to cause a late eczematous response. However, the relevance of AD worsening by ingestion of birch pollen‐related foods is still a matter of debate.
Objective
The purpose of this retrospective study was to determine how frequently birch pollen‐related foods induce a deterioration of eczema. Additionally, the diagnostic value of specific IgE (sIgE) determination was evaluated.
Methods
A total of 182 children and adults with AD and suspected birch pollen‐related food allergy underwent 261 double‐blind placebo‐controlled food challenges (DBPCFC). Total and specific IgE levels were determined prior to DBPCFC.
Results
65 patients developed allergic reactions (responders) upon DBPCFC with birch pollen‐related foods (n=103 DBPCFC). Of these, 32 patients exhibited significant deterioration of AD defined as a median increase of 15.4 SCORAD index points (95% CI 12.4‐16.3) from baseline making up 37% of all positive reactions. Responders showed significantly higher sIgE levels to birch pollen and apple as well as a higher prevalence of allergic rhinoconjunctivitis compared to non‐responders (P<.05). However, patients with late eczematous response could not be differentiated from those with isolated immediate type reactions by specific IgE levels.
Conclusion
In a subpopulation of patients with AD and birch pollen sensitization, related foods should be considered as a trigger for an aggravation of eczema. Since sufficient markers for prediction of late eczematous reactions are still lacking, DBPCFC cannot be replaced in diagnosis of birch pollen‐related foods in patients with AD.
Clinical Implications
In patients with AD and birch pollen‐allergy, birch pollen‐related foods should be considered as a provocation factor for an aggravation of disease signs and symptoms.
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Molecular allergy is based on identification, characterization and subsequent use of single allergens, being components of complex allergen sources like pollen, mites, furred animals, foods or insect venoms. Only few protein families contain relevant allergens of similar sequence and structure, carrying common IgE epitopes as the basis of cross reactivity. Used as purified or recombinant (glyco)proteins single allergens can potentially improve in-vitro diagnostics, particularly allergen-specific IgE assays through a) increased sensitivity, b) use of risk and marker allergens, c) component-resolved diagnostics (CRD). CRD can differentiate primary, species-specific from secondary, cross-reactive sensitizations to single allergens. Allergen components facilitate an increased analytical sensitivity, particularly if they are underrepresented or missing in conventional allergen extracts. They are mainly used in single assays (singleplex) for the detection of IgE, but also in a microarray format (multiplex) with 112 components from 50 allergen sources with slightly decreased analytical sensitivity. Concepts of molecular allergy can only be separately defined and utilized for each allergen source (pollen, mites, foods or insect venoms). As soon as essential singe allergens are available, their specific role in diagnostics should be defined. This requires well characterized patient cohorts from various countries, since exposure, allergic immune response and clinical relevance can vary substantially between individual subjects and geographical regions. The patient’s clinical information is essential for proper interpretation of molecular allergology results. The history and/or challenge test results will finally provide evidence, in how far a sensitization to single allergens might be clinically relevant or not.
Allergen molecules (synonyms: single allergens, allergen components) open up new horizons for the targeted allergen-specific diagnostics of immunoglobulin E (IgE) using singleplex assays. Two rationales support the targeted use of allergen molecules and, more importantly, improve test properties: (1) increased assay sensitivity (“analytical sensitivity”), particularly when important allergens are underrepresented or lacking in the extract, and (2) improved test selectivity (analytical specificity), particularly when the selected IgE repertoire against an allergen yields additional information on potential risk, possible cross-reactivity, or primary (species-specific) sensitization. However, the appropriate indication for the use of single allergens can only be established on a case-by-case basis and in an allergen-specific manner. Thus, molecular allergology is based on both conceptual and detailed knowledge. The general methodological and practical concepts of molecular allergology and their application in clinical routine form the subject of this chapter.
No Pan-European studies on the prevalence of food allergy have yet been reported. Previously published findings, generally from regional evaluations, have shown that allergies to fruits and vegetables are among the most common food allergies in adolescence and adulthood. This chapter on molecular diagnostics of fruit and vegetable allergy summarizes data from component-resolved diagnostic studies on individuals with confirmed food allergy. The main focus is on the most frequent allergies to fruits and vegetables, such as to carrot, celery root, tomato, kiwi fruit, and peach, an important representative from the Rosaceae fruits. Research demonstrates that component-resolved diagnostics can make an important contribution to improving in vitro diagnostics in food allergy. Identification of marker allergens associated with an increased risk of developing severe systemic reactions will aid in the future management of food-allergic patients.
Allergenmoleküle (Synonyme: Einzelallergene, Allergenkomponenten) eröffnen neue Möglichkeiten für die gezielte allergenspezifische Diagnostik von Immunglobulin E (IgE) in Einzelbestimmungen (Singleplex). Folgende Gründe sprechen für den gezielten Einsatz von Allergenmolekülen und verbessern vor allem die Testeigenschaften:
erhöhte Testempfindlichkeit („analytische Sensitivität“), besonders bei unterrepräsentierten oder fehlenden wichtigen Allergenen im Extrakt,
verbesserte Testselektivität (analytische Spezifität), besonders wenn das selektierte IgE-Repertoire gegen ein Allergen zusätzliche Aussagen zum potenziellen Risiko, zur möglichen Kreuzreaktivität oder zur primären (Spezies-spezifischen) Sensibilisierung gestattet.
Die richtige Indikation für den Einsatz von Einzelallergenen lässt sich allerdings nur
individuell (abhängig vom klinischen Kontext und der Vorgeschichte) und
allergenspezifisch (abhängig von der Allergenquelle und verfügbaren Einzelallergenen) und nicht einheitlich begründen.
Die molekulare Allergologie besteht somit aus Konzept- und Detailwissen. Thema dieses Kapitels sind die allgemeinen methodischen und praktischen Konzepte der molekularen Allergologie und ihre Anwendung im klinischen Alltag. Details zu speziellen diagnostischen Fragestellungen werden in den darauffolgenden Kapiteln vorgestellt.
Die häufigsten Nahrungsmittelallergien im Erwachsenenalter richten sich neben Nüssen und Leguminosen gegen Früchte und Gemüse. In einer Übersichtsarbeit aus dem Jahr 2011 (Ballmer-Weber u. Hoffmann-Sommergruber 2011) wurden die wichtigsten Forschungsergebnisse zur molekularen Diagnostik bei Frucht- und Gemüseallergie der Jahre 2009 und 2010 zusammengestellt. Das folgende Kapitel basiert auf dieser Zusammenfassung und wurde mit neuen Daten zum Thema ergänzt.
Taken into account data from which is considered a product not safe, estimate the safe level of a contaminant on food, for example, always have many unavoidable uncertainties. It cannot be overemphasized enough, that this also happens as in any other human activity. In most cases, we hope, to define as clearly as possible the eventual risk associated with particular conditions of exposure to a given substance in food. There are numerous toxic compounds that reside naturally in certain foods that unable these to be consumed above certain limits or even are fully prohibited in some other countries. Chapter starts with a clear explanation of differences and relationships between food allergy and food poisoning, continued with main allergens in food and main toxics. Finally, authors summarize different origins of toxins and allergens (natural from foods, from additives, pollutants and food processing).
Allergene Proteine sind in der Lage, in prädisponierten Individuen Th2-polarisierte Immunantworten hervorzurufen. Im Vergleich zu der heute bekannten großen Anzahl von Proteinarchitekturen kann man allergene Proteine einer sehr kleinen Zahl von Proteinfamilien zuordnen. So beschreibt die Version 27.0 der Pfam-Datenbank (http:// pfam.sanger.ac.uk/) eine Datenbank der bekannten Proteinfamilien, 14.831 Familien (Punta et al. 2012). Die SDAP, eine Strukturdatenbank allergener Proteine (https://fermi. utmb.edu/SDAP/index.html) (Ivanciuc et al. 2003) ordnet die zurzeit bekannten Allergene 130 Pfam-Proteinfamilien zu.
This report has been prepared by an EAACI task force representing the five EAACI Sections and the EAACI Executive Committee composed of specialists that reflect the broad opinion on allergy expressed by various clinical and basic specialties dealing with allergy. The aim of this report is to propose a revised nomenclature for allergic and related reactions that can be used independently of target organ or patient age group. The nomenclature is based on the present knowledge of the mechanisms which initiate and mediate allergic reactions. However, the intention has not been to revise the nomenclature of nonallergic hypersensitivity.
The availability of allergen molecules ('components') from several protein families has advanced our understanding of immunoglobulin E (IgE)-mediated responses and enabled 'component-resolved diagnosis' (CRD). The European Academy of Allergy and Clinical Immunology (EAACI) Molecular Allergology User's Guide (MAUG) provides comprehensive information on important allergens and describes the diagnostic options using CRD. Part A of the EAACI MAUG introduces allergen molecules, families, composition of extracts, databases, and diagnostic IgE, skin, and basophil tests. Singleplex and multiplex IgE assays with components improve both sensitivity for low-abundance allergens and analytical specificity; IgE to individual allergens can yield information on clinical risks and distinguish cross-reactivity from true primary sensitization. Part B discusses the clinical and molecular aspects of IgE-mediated allergies to foods (including nuts, seeds, legumes, fruits, vegetables, cereal grains, milk, egg, meat, fish, and shellfish), inhalants (pollen, mold spores, mites, and animal dander), and Hymenoptera venom. Diagnostic algorithms and short case histories provide useful information for the clinical workup of allergic individuals targeted for CRD. Part C covers protein families containing ubiquitous, highly cross-reactive panallergens from plant (lipid transfer proteins, polcalcins, PR-10, profilins) and animal sources (lipocalins, parvalbumins, serum albumins, tropomyosins) and explains their diagnostic and clinical utility. Part D lists 100 important allergen molecules. In conclusion, IgE-mediated reactions and allergic diseases, including allergic rhinoconjunctivitis, asthma, food reactions, and insect sting reactions, are discussed from a novel molecular perspective. The EAACI MAUG documents the rapid progression of molecular allergology from basic research to its integration into clinical practice, a quantum leap in the management of allergic patients.
Food allergies can newly arise in adulthood or persist following a food allergy occurring in childhood. The prevalence of primary food allergy is basically higher in children than in adults; however, in the routine practice food allergies in adulthood appear to be increasing and after all a prevalence in Germany of 3.7 % has been published. The clinical spectrum of manifestations of food allergies in adulthood is broad. Allergy symptoms of the immediate type can be observed as well as symptoms occurring after a delay, such as indigestion, triggering of hematogenous contact eczema or flares of atopic dermatitis. The same principles for diagnostics apply in this group as in childhood. In addition to the anamnesis, skin tests and in vitro tests, as a rule elimination diets and in particular provocation tests are employed. Molecular allergy diagnostics represent a major step forward, which allow a better assessment of the risk of systemic reactions to certain foodstuffs (e.g. peanuts) and detection of cross-reactions in cases of apparently multiple sensitivities. Current German and European guidelines from 2015 are available for the practical approach to clarification of food allergies. The most frequent food allergies in adults are nuts, fruit and vegetables, which can cross-react with pollen as well as wheat, shellfish and crustaceans. The therapy of allergies involves a consistent avoidance of the allogen. Detailed dietary plans are available with avoidance strategies and instructions for suitable food substitutes. A detailed counseling of affected patients by specially trained personnel is necessary especially in order to avoid nutritional deficiencies and to enable patients to enjoy a good quality of life.
Food allergy and intolerance as a cause of IBS have been investigated by several studies. In five studies, DBPCFC were done to check the role of food in determining the syndrome (16–20). In one study, none of the IBS patients had adverse reactions to food ( 19). Only one study confirmed food allergy as a cause of the syndrome in three of the 27 patients studied ( 16). The three patients showed evidence of associated atopic disease and positive skin prick tests (SPT) to common inhalant allergens. It is worth noting that some studies not using DBPCFC, but only open challenges, carried out in large series of cases with carefully selected diarrheic forms of IBS, reported a high prevalence of adverse reactions to foods, often associated with positive SPT and/or specific IgE to the same foods (21–23). In the three remaining studies, food intolerance was found to provoke symptoms of IBS, respectively, in three of 49 ( 18), in one of 23 ( 20), and in six of 27 ( 16) patients. Lactase deficiency was the mechanism of the intolerance in the food-intolerant patient of one study ( 20). Alun Jones et al. found an increase in rectal prostaglandins in the food-intolerant patients ( 16). Interestingly, in one study, nine of 10 patients with negative DBPCFC were found to be strong “placebo reactors” ( 18). Moreover, Bentley et al.'s study revealed minor psychiatric disorders in 12 of 14 patients examined by an independent psychiatrist ( 17).
Skin sensitivity to apple, carrot and potato, clinically related to birch pollinosis was investigated. Different skin test techniques using fresh fruit were compared. A simple prick test (SPT) technique with a lancet piercing the apple peel just before pricking the skin was shown to be the most practical and to give reproducible results. The allergenic activity in apple was found to be heat labile and deteriorated during storage at room temperature. Apple, carrot, potato, hazelnut and birch reactivity was transferable in Prausnitz-Küstner test like IgE antibodies. SPT reactivity to fresh material from apple, carrot and potato was investigated in 174 children of whom 128 suffered from pollen allergy. Positive SPT results were obtained almost exclusively in children who were SPT positive to a birch pollen extract. Children who noticed clinical symptoms when eating apple, raw carrot or potato were found to have a significantly larger SPT reaction than children with a negative history.
Allergy to celery is often associated with sensitization to birch and/or mugwort pollen. OBJECTIVE and
In a multi-centre study, sera from 23 patients suffering from type 1 allergy to celery and 15 patients with positive celery RAST but no clinical sensitization were compared. To examine whether cross-reactivity between celery and mugwort pollen includes cross-sensitization to birch pollen allergens, we determined cross-reacting structures in birch pollen, mugwort pollen and celery by means of immunoblotting. Inhibition studies were performed by preincubation of sera with extracts of birch pollen, mugwort pollen, and celery.
We identified three groups of proteins--homologues of Bet v 1 and birch profilin (Bet v 2) as well as a group of proteins with a molecular range of 46 to 60 kD--displaying IgE-cross-reactivity, which were shared by birch pollen and celery. Two of these groups of allergens (profilin and the 46 to 60 kD proteins) were also present in mugwort pollen. In this paper we demonstrate that most cross-reacting allergens present in mugwort pollen and celery can also be detected in birch pollen extract.
Therefore we propose, from a serological point of view, to extend the mugwort-celery syndrome to the birch-mugwort-celery syndrome.
383 predominantly adult patients (66.4% females, 33.6% males) with proved IgE-mediated food allergies (FA), including the oral allergy syndrome (OAS), were seen at the Allergy Unit of the Department of Dermatology in Zurich during the years 1990-1994. 63.2% of them had additional manifestations predominantly a pollen allergy (60.3%). The FA manifested earlier in males (36.4% before 20 years old) than in females (17.7%). The organ manifestation of symptoms of FA was most often the skin (60%) with urticaria and angioedema and the oro-gastrointestinal tract (60%), if the OAS was included. 40% had respiratory symptoms (rhinitis, asthma) and 7.6% symptoms of the cardiovascular system (anaphylactic shock). Usually, the patients showed involvement of two or more organs. 44.4% had exclusively skin symptoms, 28.7% isolated OAS and 9.1% isolated gastrointestinal manifestations. Only 6.3% had chronic symptoms of a FA, the most common symptomatology was acute (30.5%) or recurrent (63.2%). Hazelnut (36.8%), celery (celery tuber or celeriac) (36.3%), apple (25.6%) and carrot (24.8%) were found to be the most frequent food allergens: hazelnut and apple elicited mostly an OAS, whereas celery caused generalized symptoms such as acute urticaria, asthma or anaphylactic shock. These food allergens belong to the so-called pollen-associated food allergens with sensitization mainly to birch, but also to mugwort pollens. Among the food non cross-reacting with pollens, an allergy was seen to peanut (12.8%), soja (9.1%), milk (10.7%), fish (9.7%), hen's egg (5.7%) and beef meat (2.9%). These observations confirm again that in adults the type I allergic reactions to plant-derived food is commonly by a consequence of primary aerosensitization to pollen allergens. A primary ingestive sensitization in non-atopic people is rate in adults.
A protein determination method which involves the binding of Coomassie Brilliant Blue G-250 to protein is described. The binding of the dye to protein causes a shift in the absorption maximum of the dye from 465 to 595 nm, and it is the increase in absorption at 595 nm which is monitored. This assay is very reproducible and rapid with the dye binding process virtually complete in approximately 2 min with good color stability for 1 hr. There is little or no interference from cations such as sodium or potassium nor from carbohydrates such as sucrose. A small amount of color is developed in the presence of strongly alkaline buffering agents, but the assay may be run accurately by the use of proper buffer controls. The only components found to give excessive interfering color in the assay are relatively large amounts of detergents such as sodium dodecyl sulfate, Triton X-100, and commercial glassware detergents. Interference by small amounts of detergent may be eliminated by the use of proper controls.
The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Food and Agriculture Organization of the United nations concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitations of its frontiers or boundaries. The opinions expressed in this publication are those of the author(s) alone and do not imply any opinion on the part of the FAO.
Food allergy is a group of distinct clinico-pathological entities that have an immunological basis in common, and in which an abnormal or exaggerated immunological response to a specific food leads to disease. Some clinical pictures involving multiple organ system (anaphylaxis) are potentially fatal. The data on the incidence, prevalence, mortaility rate and food products involved in food-induced anaphylaxis and the evolution of food sensitization compared with changes in eating habits are not very reliable. In the present study we analysed, over a period of 9 years (1984–1992), a group of 580 patients with pathological reactions to foods, 60 of which presented severe, near-fatal reactions. We sought eh etiologic components and food sensitization in comparison with the principle tendencies of food consumption in France. Food products most frequently incriminated in anaphylactic reactions are not of a primary nutritional importance: celery (30%), crustaceans (17%), fish (13%), peanuts (12%), mango (6%), mustrad (3%), but they are often hidden allergens in commercial foods. The sensitization to food products in the group of 580 patients reveals, in decreasing order of frequency: wheat (39%), peanuts (37%), crab (34%), celery (30%), soy (30%). Compared with previous data, the frequency of sensitization to different foods has changed; for instance, the sensitizations to wheat, soy, peanuts, celery, mustard, rice, are definitely increasing. The increased consumption and more attentive clinical research may be the reasons for this evolution. For products such as egg and pork, the data are stable and parallel with consumpotion, whilst for other products like milk and other dairy products, the increased consumption is accompanied by a decrease of the incidence of sensitization. The activity to some allergens may be affected by the way of preparing the food.
A protein determination method which involves the binding of Coomassie Brilliant Blue G-250 to protein is described. The binding of the dye to protein causes a shift in the absorption maximum of the dye from 465 to 595 nm, and it is the increase in absorption at 595 nm which is monitored. This assay is very reproducible and rapid with the dye binding process virtually complete in approximately 2 min with good color stability for 1 hr. There is little or no interference from cations such as sodium or potassium nor from carbohydrates such as sucrose. A small amount of color is developed in the presence of strongly alkaline buffering agents, but the assay may be run accurately by the use of proper buffer controls. The only components found to give excessive interfering color in the assay are relatively large amounts of detergents such as sodium dodecyl sulfate, Triton X-100, and commercial glassware detergents. Interference by small amounts of detergent may be eliminated by the use of proper controls.
The purpose of this study was to determine whether patients allergic to one fish species can safely eat other fish species. Eleven atopic, food-allergic children and young adults with histories consistent with IgE-mediated fish hypersensitivity were skin prick tested to 10 fish species. Skin prick tests (SPTs) were positive to all 10 fish in eight of the 11 patients, and the remaining three patients had at least two positive fish SPTs. Positive oral challenges occurred to only one fish in seven of the patients, to two fish species in one patient, and to three fish species in two patients. One patient did not react to any of the fish tested. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot analyses were performed on raw and cooked protein extracts from nine of the 10 fish species used in SPTs. Several protein bands in the raw-fish extracts appeared to denature with cooking and form high molecular weight conglomerates. Immunoblot analyses with sera from documented fish-allergic patients demonstrated specific IgE binding to protein bands from fish to which patients were not clinically allergic, as determined by oral challenge. In ELISA-inhibition assays, the concentration of fish antigen required to achieve 50% inhibition was similar for fish to which the patients were clinically allergic as compared to fish to which they were clinically tolerant. SPT and in vitro evidence of IgE-specific cross-reactivity does not necessarily correlate with symptomatic fish allergy. In addition, these fish-hypersensitive patients were able to consume one or more other fish species without adverse allergic reactions.
229 patients who showed an immediate-type allergy to one or more specific foodstuffs diagnosed from 1983 to 1987 at the Allergy Unit of the Department of Dermatology, Zurich University Hospital, have been studied. Of these predominantly adult patients, 66 (28.8%) were male and 163 (71.2%) female. 70.7% of the food allergic patients also showed one or more atopic manifestations, in particular 53.3% a pollinosis. The food-induced symptoms included involvement of the skin (rashes, urticaria, angioedema) (46.4), the respiratory tract (asthma, rhinorrhea) (24.1%) and the gastrointestinal tract (21.8%). 14.4% reacted with anaphylactic shock. Generally the patients showed involvement of two or more organs. In only 7% of all cases was food allergy responsible for a chronic allergic condition such as urticaria, asthma or intestinal symptoms. Concerning diagnostic procedures, a careful case history and various techniques of skin testing, particularly with raw foods, are helpful. RAST was negative in more of the half of the diagnosed cases. Confirming previously published work, food allergens were mainly found among vegetables, such as celery with 44.5%, followed by carrots (14.4%) and spices (16.6%). In these cases there were cross-reactivities between birch or mugwort pollens. Cheese and milk allergies (14%) were present in patients without previous atopic manifestations. We confirm that the so-called "celery-carrot-mugwort-spice-syndrome" is more frequent in females (81.4%) than in males. In 24 cases celery-spice sensitization was responsible for severe anaphylactic reactions.
Skin prick tests (SPT) with various celery, carrot and potato preparations (raw, cooked, cooking water of each vegetable and allergen extracts) as well as specific IgE determinations by RAST to celery mix, celeriac (or root celery), stick celery and heated celery extracts were performed in 70 patients with positive prick or intracutaneous tests to birch and/or mugwort pollens and celery (extract and/or raw). 94% of the patients showed positive prick tests to raw celeriac, 36% to cooked celeriac and 8/13 to cooking water. Celery-birch positive patients (n = 13) showed negative or low RASTs to heated celery extracts and to stick celery. By contrast, in the celery-mugwort sensitive patients (n = 6) the celery RASTs with heated celery extracts remained clearly positive and high RAST values to stick celery could be found. Celery-birch-mugwort-association (n = 22) favoured more positive results with relatively high values of RAST to celeriac. The results of homologous and heterologous RAST inhibition experiments with birch, mugwort, unheated and heated celery (100 degrees C) carried out in nine celery-RAST positive sera are also discussed.
There is now enough experience with the use of double-blind, placebo-controlled, food challenge (DBPCFC) to recommend its use as an office procedure for most patients complaining of adverse reactions to foods. This manual discusses the practical methods required for the allergist to undertake DBPCFC in the office. Thorough histories supplemented by food allergen skin testing are used to design a DBPCFC that carefully attempts to reproduce the history of food-induced symptoms described by the patient. Precautions that must be taken are delineated before challenge, as is treatment that may be required if a reaction occurs. For those foods to which challenges are positive, longitudinal evaluation with repeated challenge at appropriate intervals help to determine whether or not the problem will resolve over a period of time.
In 20 patients, the ingestion of celery was responsible for mucocutaneous symptoms (generalized urticaria and angioedema) (18/20) and respiratory disorders (7/20). Four cases of systemic anaphylaxis were observed. The main associated allergic disorder was pollinosis (16/20). Food allergy to other vegetable products, mainly other Umbelliferae and apples, coexisted with celery allergy in 12 cases. It was found that celery allergy is mediated by IgE antibodies: it is easily diagnosed by skin tests (fresh extracts of celery may be used) and by adequate RAST (17 positive results). Cosensitization with mugwort pollen (14 cases) and birch pollen (9 cases) was found. Celery allergens responsible for clinical sensitization originate chiefly in the tuber and are at least partly thermally labile. The frequent association with pollen sensitization suggests the existence of common antigenic epitopes in celery extracts and mugwort and birch pollens. The immunologic investigations carried out so far (RAST inhibition and immunoprint) seem to support this hypothesis.
This study is an attempt to determine the role of double-blind food challenge (DBFC) in suspected food sensitivity in the adult as compared wih established tests of food allergy, including the skin test, RAST, and leukocyte histamine release (LHR) to specific food antigens. Twenty-two subjects (ages 18 to 67) with histories of reactions to foods were challenged with freeze-dried food or placebo in opaque dye-free capsules, in increasing doses over a 90 min span to a total of 13 to 15 gm. This was repeated twice at weekly intervals by similar DBFC. DBFC was preceded by skin testing and venapuncture for RAST and LHR studies. Patients were kept under observation for 2 hr, after which each was asked to maintain a detailed diary of related symptoms and food ingested over the following week. Of 46 DBFCs, 13 (21%) were positive. The correlation with positive skin tests and positive DBFC was 4/13 (30%). The correlation with positive LHR and positive DBFC was lower at 2/13 (15%), and 1/13 (7.6%) with RAST. We concluded that DBFC is an effective test of adult food sensitivity compared with tests usually performed and should be used when the diagnosis is in doubt.
Individuals suffering from immediate hypersensitivity (type-I allergy) to a particular pollen frequently display intolerance to several foods of plant origin. In this respect, individuals sensitized to birch pollen and/or mugwort pollen frequently display type-I allergic symptoms after ingestion of celery. In this study, we expressed the major allergenic protein of celery, Api g 1, which is responsible for the birch-celery syndrome, in the form of a non-fusion protein. The open reading frame of the cDNA of Api g 1 codes for a protein of 153 amino acids with a molecular mass of 16.2 kDa and 40% identity (60% similarity) to the major allergen of birch pollen, Bet v 1. Furthermore, Api g 1 exhibited similar characteristics to (a) two proteins in parsley induced by fungal infection, (b) the major tree pollen allergens and (c) pathogenesis-related and stress-induced proteins in other plant species. The reactivity of recombinant Api g 1 with IgE antibodies present in sera from celery intolerant patients was comparable to that of the natural celery allergen. Cross-reactivity with Bet v 1 was proven by cross-inhibition experiments, which provides further support for the existence of the birch-celery syndrome and for the suggestion that allergies to some vegetable foods are epiphenomena to allergies caused by inhalation of tree pollen.
In this study serum samples collected from 20 patients with birch pollen allergy were investigated. All patients had experienced allergic symptoms after contact with or ingestion of particular fresh fruits and vegetables known as birch pollen-related foods.
Serum samples were tested by means of immunoblotting for IgE reactivities with proteins in extracts of birch pollen, apple, pear, celery, carrot, and potato. Anti-Bet v 1 and anti-Bet v 2 antibodies were used to investigate cross-reactivity. Inhibition studies were performed by preincubation of sera with recombinant Bet v 1 and Bet v 2.
IgE binding to proteins, corresponding to the major birch pollen allergen Bet v 1 and to Bet v 2 (birch pollen profilin) could be observed. An allergen homologous to Bet v 1 could be detected in apple, pear, and celery when a Bet v 1-specific monoclonal antibody was used. Testing a polyclonal rabbit anti-Bet v 2 antibody with extracts of the respective plants revealed the presence of profilins in every source tested. Inhibition with recombinant Bet v 1 and Bet v 2 led to complete blocking or marked reduction of IgE binding to proteins of comparable molecular weights in the respective food extracts, indicating IgE cross-reactivity.
Our results indicate that many plant-derived food agents contain proteins with high homology to the birch pollen allergens Bet v 1 and Bet v 2 and must therefore be considered as potentially threatening for patients with tree pollen allergy.
Food additives can induce a wide range of adverse reactions in sensitive individuals. A prevalence of 0.03% to 0.23% is estimated. The complexity of the different pathophysiologic mechanisms possibly involved in the allergic (immunologic) or in the intolerant (nonimmunologic) reactions to food additives continues to create great difficulties in the understanding of such conditions. From the clinical point of view it is useful to make a distinction between an intolerance reaction and intolerance provocation. The pathogenic mechanisms of adverse reactions to the azo dye tartrazine and to sulfite preservatives are discussed briefly. Due to the lack of reliable skin or in vitro tests, the diagnosis of an intolerance to food additives is still based on placebo-controlled oral provocation tests. Two typical cases of a "restaurant syndrome" due to sulfite allergy or sensitivity are described, as well as a case of disulfite-induced urticaria-vasculitis and a case of anaphylactoid purpura associated with tartrazine and benzoates.
The rates of sensitization and allergy to four birch pollen related plant foods were investigated in a group of 167 patients who were sensitive to at least one kind of pollen and one particular food. Sensitivity was concluded from a positive skin prick test or the determination of specific IgE, whereas allergy was based on anamnestic data. The positivity rates for sensitization and allergy, respectively, were: apple, 93 and 84%; hazelnut, 90 and 78%; celery, 70 and 14%; carrot, 60 and 37%. Comparative testing by skin prick test and enzyme allergosorbent test (EAST) with extract from native and microwaved (750 W, 30 min, 100 degrees C) celery root was performed on 46 of these patients. At least one positive test result (either prick test or EAST) was obtained for native celery in 36/46 (78%) and for heated celery in 20/46 (43%) of these patients. Although the concordance between the EAST and the skin test was very low, extended control experiments of both test procedures revealed no evidence for nonspecificity. Immunoblot analyses of extract from native celery and sera of 60 patients with a positive EAST (class > or = 2, > or = 0.7 U/ml) for celery resulted in the following rates of IgE binding to known cross-reactive celery allergens: Api g 1:33%, celery profilin: 17%; multiple bands most probably due to carbohydrate epitopes: 32%. The rate of binding to other allergens was below 10%. Since these three important structures are also present in birch pollen, no allergen could be identified as a candidate to mediate an exclusive celery/mugwort association. Investigation of extract from native and heated celery by immunoblotting pointed to a high lability of Api g 1, whereas profilin and carbohydrate epitopes appeared to be more resistant to heat. It has been concluded that sensitization to celery in German patients is without clinical significance in the majority of cases, in contrast to other birch-pollen-related plant foods such as apple and hazelnut. For the particular kind of extract used, neither the EAST nor the skin test alone represents an appropriate diagnostic method for testing sensitization to celery.
Any new diagnostic test should be validated by standard procedures, and must be validated by the outcome of double-blind, placebo-controlled food challenges (DBPCFC), except in infants, with strict adherence to the EAACI guidelines. Available data should include calculations on sensitivity, specificity, predictive values, and concordance and must be calculated on the basis of patients in whom the diagnosis has been established by DBPCFC. Furthermore, data on possible cross-reacting foods and their clinical relevance should be available.
Up to 70% of patients with tree pollen allergy display allergic symptoms when eating certain fruits and vegetables. Homologous proteins with allergenic features are present in a wide range of plant species and can cause allergic reactions.
The aim of this study was to evaluate recombinant Api g 1, a major celery allergen, for in vivo and in vitro diagnosis of celery allergy in populations from Davos, Switzerland, and Montpellier, France.
A group of patients with celery and birch pollen allergy from Davos was tested, and the results from those tests were compared with results from a group of patients allergic to celery from Montpellier. Skin prick tests were performed with a commercial celery extract, crude celery, and purified recombinant Api g 1. Quantitative and qualitative serology was done with natural and recombinant allergens by means of RASTs and immunoblotting.
Recombinant Api g 1 allowed accurate in vivo diagnosis of celery allergy in all patients from the Swiss group. RAST results with celery extract were negative in 8 of 24 patients; results of immunoblotting with celery extract were negative in 4 of 24 patients, and results of immunoblotting with recombinant (r)Api g 1 were negative in 8 of 24 patients. In the French group 11 of 12 patients had a positive skin reaction with crude celery extract, but only 2 patients reacted with rApi g 1. RAST results for celery were positive in 8 of 12 patients. In immunoblotting experiments 8 patient sera displayed IgE directed against various celery allergens, whereas no patients sera had rApi g 1-specific IgE.
Our results document that rApi g 1 allows accurate in vivo diagnosis only in areas where birch trees are common. In areas where no birch trees grow, primary sensitization takes place through different pollen allergens (eg, mugwort pollen). Moreover, it became evident that birch pollen and celery allergy are highly related in Central Europe, whereas in Southern Europe the mugwort-celery type is predominant.
Tree nuts are a common cause of food allergy in Europe. However, few studies deal with real food allergy to hazelnuts in subjects believed to be allergic to this food.
We sought to select subjects with a history of allergic reactions on ingestion of hazelnut and determine how many of these have true allergy by means of the double-blind, placebo-controlled food challenge (DBPCFC).
Eighty-six subjects with a history of symptoms after hazelnut ingestion were recruited from 3 allergy centers (Milan, Zurich, and Copenhagen). All subjects underwent skin prick tests (SPTs) with aeroallergens and hazelnut, as well as having their specific hazelnut IgE levels determined. Diagnosis of clinical relevant food allergy was made on the basis of the DBPCFC.
Sixty-seven (77.9%) of 86 subjects had a positive DBPCFC result; 8 were placebo responders, and 11 were nonresponders. Of the 11 nonresponders, 4 had positive open-challenge test results. Of the DBPCFC-positive subjects, 87% also had positive skin test responses to birch pollen extract. Specific IgE determination for hazelnut (positive CAP response >/=0.7 kU/L [ie, class 2]) showed a sensitivity of 0.75, a positive predictive value (PPV) of 0.92, a specificity of 0.16, and a negative predictive value (NPV) of 0.05. Skin tests with commercial hazelnut extract produced a sensitivity of 0.89, a PPV of 0.92, a specificity of 0.05, and an NPV of 0.05. Skin tests with natural food produced a sensitivity of 0.88, a PPV of 0.94, a specificity of 0.27, and an NPV of 0.15.
This study shows that hazelnut is an allergenic source that can cause real food allergy, as confirmed by DBPCFC. Skin and IgE tests demonstrated reasonable sensitivity and PPV but a very low specificity and NPV, thus implying that these should not be used to validate the diagnosis of food allergy to hazelnut.
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IgE reactivity to Api g 1, a major celery allergen, in a Central European population is based on pri-mary sensitization by Bet v 1 Receive tables of contents by e-mail To receive the tables of contents by e-mail, sign up through our Web site
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Hoffmann-Sommergruber K, Demoly P, Crameri R, Breiteneder H, Ebner C, Laimer da Camara Machado M, et al. IgE reactivity to Api g 1, a major celery allergen, in a Central European population is based on pri-mary sensitization by Bet v 1. J Allergy Clin Immunol 1999;104:478-84. Receive tables of contents by e-mail To receive the tables of contents by e-mail, sign up through our Web site at http://www.mosby.com/jaci Choose E-mail notification. Simply type your e-mail address in the box and click the Subscribe button.
The European Academy of Allergology and Clinical Immunology
Allergen standardization and skin tests. The European Academy of Allergology and Clinical Immunology. Allergy 1993;48(Suppl 14):48-82.
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IgE-vermittelte Nahrungsmittelallergie bei 383 Patienten unter Berücksichtigung des oralen Allergie-Syndroms
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Allergen standardization and skin tests
- The European Academy of Allergology and Clinical Immunology
Nahrungsmittelallergien 1983-1987
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