Barbara K. Ballmer-Weber

Standardization of food challenges in patients with immediate reactions to foods – position paper from the European Academy of Allergology and Clinical Immunology

At present, the double blind placebo controlled foodchallenge(DBPCFC)representstheonlywaytoestablishorruleoutanadversereactiontoafoodinolderchildrenand adults, whereas an open challenge controlled bytrained personnel is sufficient in infants and youngchildren (1). The challenge procedure is not, however,C.Bindslev-Jensen

Current Understanding of Cross-Reactivity of Food Allergens and Pollen

Abstract: Pollen‐allergic patients frequently present allergic symptoms after ingestion of several kinds of plant‐derived foods. The majority of these reactions is caused by four distinct cross‐reactive structures that are present in birch pollen. Proteins that share common epitopes with Bet v 1, the major birch pollen allergen, occur in pollens of several tree species: apples, stone fruits, celery, carrot, nuts, and soybeans. Approximately 70% of our patients who are allergic to birch pollen may experience symptoms after consumption of foods from these groups. In contrast, two minor allergenic structures—profilins and cross‐reactive carbohydrate determinants (CCD)—that sensitize approximately 10‐20% of all pollen‐allergic patients are also present in grass pollen and weed pollen. Moreover, IgE‐binding proteins related to the birch pollen minor allergen Bet v 6 have been found in many vegetable foods such as apple, peach, orange, lychee fruit, strawberry, persimmon, zucchini, and carrot. Frequently, the occurrence of cross‐reactive IgE antibodies is not correlated with the development of clinical food allergy. In particular, the clinical relevance of sensitization to CCD is doubtful. Generally, pollen‐related allergens tend to be more labile during heating procedures and in the digestive tract compared to allergens from classical allergenic foods such as peanut. However, recent DBPCFC studies have shown that both cooked celery and roasted hazelnuts still pose an allergenic risk for pollen‐sensitized subjects. Since pathogenesis‐related proteins share several common features with allergens and both the Bet v 1 and the Bet v 6‐related food allergens are defense‐related proteins, approaches to introduce such proteins as a measure to protect plants against diseases should be performed with caution as they may increase the allergenicity of these crops.

EAACI food allergy and anaphylaxis guidelines: diagnosis and management of food allergy

Food allergy can result in considerable morbidity, impact negatively on quality of life, and prove costly in terms of medical care. These guidelines have been prepared by the European Academy of Allergy and Clinical Immunologys (EAACI) Guidelines for Food Allergy and Anaphylaxis Group, building on previous EAACI position papers on adverse reaction to foods and three recent systematic reviews on the epidemiology, diagnosis, and management of food allergy, and provide evidence‐based recommendations for the diagnosis and management of food allergy. While the primary audience is allergists, this document is relevant for all other healthcare professionals, including primary care physicians, and pediatric and adult specialists, dieticians, pharmacists and paramedics. Our current understanding of the manifestations of food allergy, the role of diagnostic tests, and the effective management of patients of all ages with food allergy is presented. The acute management of non‐life‐threatening reactions is covered in these guidelines, but for guidance on the emergency management of anaphylaxis, readers are referred to the related EAACI Anaphylaxis Guidelines.

Soybean (Glycine max) allergy in Europe: Gly m 5 (β-conglycinin) and Gly m 6 (glycinin) are potential diagnostic markers for severe allergic reactions to soy.

BACKGROUND Soybean is considered an important allergenic food, but published data on soybean allergens are controversial. OBJECTIVE We sought to identify relevant soybean allergens and correlate the IgE-binding pattern to clinical characteristics in European patients with confirmed soy allergy. METHODS IgE-reactive proteins were identified from a soybean cDNA expression library, purified from natural soybean source, or expressed in Escherichia coli. The IgE reactivity in 30 sera from subjects with a positive double-blind, placebo-controlled soybean challenge (n = 25) or a convincing history of anaphylaxis to soy (n = 5) was analyzed by ELISA or CAP-FEIA. RESULTS All subunits of Gly m 5 (beta-conglycinin) and Gly m 6 (glycinin) were IgE-reactive: 53% (16/30) of the study subjects had specific IgE to at least 1 major storage protein, 43% (13/30) to Gly m 5 , and 36% (11/30) to Gly m 6. Gly m 5 was IgE-reactive in 5 of 5 and Gly m 6 in 3 of 5 children. IgE-binding to Gly m 5 or Gly m 6 was found in 86% (6/7) subjects with anaphylaxis to soy and in 55% (6/11) of subjects with moderate but only 33% (4/12) of subjects with mild soy-related symptoms. The odds ratio (P < .05) for severe versus mild allergic reactions in subjects with specific IgE to Gly m 5 or Gly m6 was 12/1. CONCLUSION Sensitization to the soybean allergens Gly m 5 or Gly m 6 is potentially indicative for severe allergic reactions to soy.

Testing for IgG4 against foods is not recommended as a diagnostic tool: EAACI Task Force Report.

Serological tests for immunoglobulin G4 (IgG4) against foods are persistently promoted for the diagnosis of food‐induced hypersensitivity. Since many patients believe that their symptoms are related to food ingestion without diagnostic confirmation of a causal relationship, tests for food‐specific IgG4 represent a growing market. Testing for blood IgG4 against different foods is performed with large‐scale screening for hundreds of food items by enzyme‐linked immunosorbent assay‐type and radioallergosorbent‐type assays in young children, adolescents and adults. However, many serum samples show positive IgG4 results without corresponding clinical symptoms. These findings, combined with the lack of convincing evidence for histamine‐releasing properties of IgG4 in humans, and lack of any controlled studies on the diagnostic value of IgG4 testing in food allergy, do not provide any basis for the hypothesis that food‐specific IgG4 should be attributed with an effector role in food hypersensitivity. In contrast to the disputed beliefs, IgG4 against foods indicates that the organism has been repeatedly exposed to food components, recognized as foreign proteins by the immune system. Its presence should not be considered as a factor which induces hypersensitivity, but rather as an indicator for immunological tolerance, linked to the activity of regulatory T cells. In conclusion, food‐specific IgG4 does not indicate (imminent) food allergy or intolerance, but rather a physiological response of the immune system after exposition to food components. Therefore, testing of IgG4 to foods is considered as irrelevant for the laboratory work‐up of food allergy or intolerance and should not be performed in case of food‐related complaints.

Eczematous reactions to food in atopic eczema: position paper of the EAACI and GA2LEN.

Food allergy and atopic eczema (AE) may occur in the same patient. Besides typical immediate types of allergic reactions (i.e. noneczematous reactions) which are observed in patients suffering from AE, it is clear that foods, such as cow’s milk and hen’s eggs, can directly provoke flares of AE, particularly in sensitized infants. In general, inhaled allergens and pollen‐related foods are of greater importance in older children, adolescents and adults. Clinical studies have revealed that more than 50% of affected children with AE that can be exacerbated by certain foods will react with a worsening of skin eczema either alone or in addition to immediate symptoms. Adolescents and adults may also react to foods, but reactions to ‘classical’ food allergens, such as hen’s eggs and cow’s milk, are not as common as in childhood. Some patients with AE do react to pollen‐associated foods. Food‐induced eczema should not be neglected by the allergologist: On the one hand, food can be a relevant trigger factor of persistent moderate‐to‐severe AE; on the other hand, unnecessary diets which are not based on a proper diagnosis may lead to malnutrition and additional psychological stress on patients suffering from AE. Eczematous reactions to food can only be diagnosed by a thorough diagnostic procedure, taking into account the patient’s history, the degree of sensitization and the clinical relevance of the sensitization. The latter has often to be proven by oral food challenges. Upon oral food challenge it is most important to evaluate the status of the skin with an established score (e.g. SCORAD, EASI) after 24 h and later because otherwise worsening of eczema will be missed.

Roasted hazelnuts – allergenic activity evaluated by double‐blind, placebo‐controlled food challenge

Background: Allergy to hazelnuts is a common example of birch pollen related food allergy. Symptoms upon ingestion are often confined to the mouth and throat, but severe systemic reactions have been described in some patients. The aim of the study was to evaluate the reduction in allergenicity by roasting of the nuts.

Wheat IgE-Mediated Food Allergy in European Patients: α-Amylase Inhibitors, Lipid Transfer Proteins and Low-Molecular-Weight Glutenins

BACKGROUND Three main problems hamper the identification of wheat food allergens: (1) lack of a standardized procedure for extracting all of the wheat protein fractions; (2) absence of double-blind, placebo-controlled food challenge studies that compare the allergenic profile of Osbornes three protein fractions in subjects with real wheat allergy, and (3) lack of data on the differences in IgE-binding capacity between raw and cooked wheat. METHODS Sera of 16 wheat-challenge-positive patients and 6 patients with wheat anaphylaxis, recruited from Italy, Denmark and Switzerland, were used for sodium dodecyl sulfate-polyacrylamide gel electrophoresis/immunoblotting of the three Osbornes protein fractions (albumin/globulin, gliadins and glutenins) of raw and cooked wheat. Thermal sensitivity of wheat lipid transfer protein (LTP) was investigated by spectroscopic approaches. IgE cross-reactivity between wheat and grass pollen was studied by blot inhibition. RESULTS The most important wheat allergens were the alpha-amylase/trypsin inhibitor subunits, which were present in all three protein fractions of raw and cooked wheat. Other important allergens were a 9-kDa LTP in the albumin/globulin fraction and several low-molecular-weight (LMW) glutenin subunits in the gluten fraction. All these allergens showed heat resistance and lack of cross-reactivity to grass pollen allergens. LTP was a major allergen only in Italian patients. CONCLUSIONS The alpha-amylase inhibitor was confirmed to be the most important wheat allergen in food allergy and to play a role in wheat-dependent exercise-induced anaphylaxis, too. Other important allergens were LTP and the LMW glutenin subunits.Background: Three main problems hamper the identification of wheat food allergens: (1) lack of a standardized procedure for extracting all of the wheat protein fractions; (2) absence of double-blind, placebo-controlled food challenge studies that compare the allergenic profile of Osborne’s three protein fractions in subjects with real wheat allergy, and (3) lack of data on the differences in IgE-binding capacity between raw and cooked wheat. Methods: Sera of 16 wheat-challenge-positive patients and 6 patients with wheat anaphylaxis, recruited from Italy, Denmark and Switzerland, were used for sodium dodecyl sulfate-polyacrylamide gel electrophoresis/immunoblotting of the three Osborne’s protein fractions (albumin/globulin, gliadins and glutenins) of raw and cooked wheat. Thermal sensitivity of wheat lipid transfer protein (LTP) was investigated by spectroscopic approaches. IgE cross-reactivity between wheat and grass pollen was studied by blot inhibition. Results: The most important wheat allergens were the α-amylase/trypsin inhibitor subunits, which were present in all three protein fractions of raw and cooked wheat. Other important allergens were a 9-kDa LTP in the albumin/globulin fraction and several low-molecular-weight (LMW) glutenin subunits in the gluten fraction. All these allergens showed heat resistance and lack of cross-reactivity to grass pollen allergens. LTP was a major allergen only in Italian patients. Conclusions: The α-amylase inhibitor was confirmed to be the most important wheat allergen in food allergy and to play a role in wheat-dependent exercise-induced anaphylaxis, too. Other important allergens were LTP and the LMW glutenin subunits.

EAACI Molecular Allergology User's Guide

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 Users 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.

Influence of food processing on the allergenicity of celery: DBPCFC with celery spice and cooked celery in patients with celery allergy

Background: Celery root is often consumed in a processed form as a cooked vegetable or as a spice. So far, however, there has been no information about the allergenicity of processed celery in celery‐allergic patients.