Karin Hoffmann-Sommergruber

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.

Microarrayed allergen molecules: diagnostic gatekeepers for allergy treatment

Type I allergy is an immunoglobulin E (IgE)‐mediated hypersensitivity disease affecting more than 25% of the population. Currently, diagnosis of allergy is performed by provocation testing and IgE serology using allergen extracts. This process defines allergen‐containing sources but cannot identify the disease‐eliciting allergenic molecules. We have applied microarray technology to develop a miniaturized allergy test containing 94 purified allergen molecules that represent the most common allergen sources. The allergen microarray allows the determination and monitoring of allergic patients’ IgE reactivity profiles to large numbers of disease‐causing allergens by using single measurements and minute amounts of serum. This method may change established practice in allergy diagnosis, prevention, and therapy. In addition, microarrayed antigens may be applied to the diagnosis of autoimmune and infectious diseases.

The epidemiology of food allergy in Europe: a systematic review and meta-analysis

Food allergy (FA) is an important atopic disease although its precise burden is unclear. This systematic review aimed to provide recent, up‐to‐date data on the incidence, prevalence, time trends, and risk and prognostic factors for FA in Europe. We searched four electronic databases, covering studies published from 1 January 2000 to 30 September 2012. Two independent reviewers appraised the studies and qualified the risk of bias using the Critical Appraisal Skills Programme tool. Seventy‐five eligible articles (comprising 56 primary studies) were included in a narrative synthesis, and 30 studies in a random‐effects meta‐analysis. Most of the studies were graded as at moderate risk of bias. The pooled lifetime and point prevalence of self‐reported FA were 17.3% (95% CI: 17.0–17.6) and 5.9% (95% CI: 5.7–6.1), respectively. The point prevalence of sensitization to ≥1 food as assessed by specific IgE was 10.1% (95% CI: 9.4–10.8) and skin prick test 2.7% (95% CI: 2.4–3.0), food challenge positivity 0.9% (95% CI: 0.8–1.1). While the incidence of FA appeared stable over time, there was some evidence that the prevalence may be increasing. There were no consistent risk or prognostic factors for the development or resolution of FA identified, but sex, age, country of residence, familial atopic history, and the presence of other allergic diseases seem to be important. Food allergy is a significant clinical problem in Europe. The evidence base in this area would benefit from additional studies using standardized, rigorous methodology; data are particularly required from Eastern and Southern Europe.

Quantitative IgE inhibition experiments with purified recombinant allergens indicate pollen-derived allergens as the sensitizing agents responsible for many forms of plant food allergy

BACKGROUND Type I allergic symptoms in the oropharyngeal mucosa upon contact with plant-derived food in patients with pollen allergies have been termed oral allergy syndrome (OAS). IgE cross-reactivity between pollen and food allergens represents the molecular basis for this phenomenon. The sensitizing allergen source (pollen or plant food) in OAS is a controversial issue. OBJECTIVE We sought to determine the primary sensitizing molecules in patients with OAS. METHODS We used recombinant birch pollen (rBet v 1 and rBet v 2) and plant food allergens (apple, rMal d 1; celery, rApi g 1; and carrot, rDau c 1), as well as natural pollen (birch and timothy grass) and plant food (apple, peach, kiwi, hazelnut, celery, and carrot) allergens, to identify cross-reactive allergens by using qualitative immunoblot inhibitions. In addition, we determined the percentage of plant food-specific IgE that can be preadsorbed with recombinant and natural pollen allergens by quantitative RAST inhibitions by using sera from 71 patients with OAS. RESULTS Preincubation of sera with recombinant and natural pollen allergens led to an almost complete inhibition of IgE binding to plant food allergens in Western blots, as well as in RAST inhibition experiments. In contrast, recombinant plant food allergens poorly inhibited IgE binding to Bet v 1. CONCLUSION Most IgE epitopes in plant food recognized by patients with OAS are resembled by pollen allergens. Thus pollen allergens may be responsible for the elicitation and maintenance of OAS.

Efficacy of birch-pollen immunotherapy on cross-reactive food allergy confirmed by skin tests and double-blind food challenges

Background The effect of birch‐pollen immunotherapy (IT) on cross‐reactive food allergies is controversial.

Plant allergens and pathogenesis-related proteins. What do they have in common?

In the recent past a great number of proteins causing type 1 allergic reactions in humans have been isolated and characterised. The main sources containing allergens are plants, mites, fungal spores and insects. Plant-derived allergens may either be taken in from the upper respiratory tract or they are present in a vast range of plant food causing food allergic reactions. Compared to the enormous amount of different plant proteins only a small number out of them are identified as a an allergen at present. Looking at the allergen encoding sequences, relationships by sequence similarity can be found quite frequently to a restricted number of plant protein families. Predominantly, these protein families are seed storage proteins, structural proteins and proteins involved in the defence-related system – pathogenesis-related proteins. In the following, a short overview of a number of pathogenesis-related protein families is presented in relation to the already known homologous plant allergens.

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.

Mucosal co-application of lactic acid bacteria and allergen induces counter-regulatory immune responses in a murine model of birch pollen allergy

Recent epidemiological studies and clinical trials suggest a possible role of certain lactic acid bacteria (LAB) strains in the prevention of allergic diseases. In this study, we aimed at evaluating the immunomodulatory potential of two LAB strains, Lactococcus lactis and Lactobacillus plantarum, for prophylaxis and therapy of allergic immune responses. Both LAB strains-induced high levels of IL-12 and IFN-gamma in naive murine spleen cell cultures. Intranasal co-application with recombinant Bet v 1, the major birch pollen allergen, prior or after allergic sensitization, led to increased levels of allergen-specific IgG2a antibodies and in vitro IFN-gamma production, indicating a shift towards Th1 responses. Successful immunomodulation by the mucosal pre-treatment was further demonstrated by suppression of allergen-induced basophil degranulation. We conclude that these LAB strains in combination with an allergen could be promising candidates for mucosal vaccination against type I allergy.

The promoter of an apple Ypr10 gene, encoding the major allergen Mal d 1, is stress- and pathogen-inducible☆

Mal d 1 protein, constituting the major apple allergen, was classified as pathogenesis-related protein 10 (PR-10) on the basis of sequence homologies, although its induction by pathogens or stress has not been demonstrated so far. Here we report the promoter activity of a member of the apple Ypr10 gene family and the inducibility of its gene product Mal d 1. The genomic clone and the promoter sequence of Ypr10*a from Malus domestica have been isolated and characterized. For gene regulation studies the promoter was translationally fused to the uidA reporter gene and expressed in stable transformed Nicotiana tabacum. A total of 1.25 kb of 5′ regulating sequence turned out to be necessary to direct strong β-glucuronidase (GUS) expression. Besides the already known occurrence of Mal d 1 in ripe fruits, Ypr10 genes were found to be highly expressed only in old leaves, but can be induced in young leaves by multiple stress factors. Application of abiotic stimuli, like salicylic acid and reduced glutathione significantly increased both, Ypr10*a-GUS activity in transgenic tobacco and transcriptional and translational expression of Mal d 1 in young apple leaves. Virus infection of the transformed tobacco plants strongly induced Ypr10*a-GUS transgene expression. After treatment with fungal elicitors a clear increase in GUS activity and Mal d 1 expression was observed in young tobacco and apple leaves, respectively.

Cross-reactive and species-specific immunoglobulin E epitopes of plant profilins: an experimental and structure-based analysis.

Background Profilins are cross‐reactive plant allergens responsible for multiple pollen sensitization and pollen‐associated food allergy. While it is assumed that profilins from different species are immunologically equivalent, some studies suggest partial or even lacking IgE cross‐reactivity between certain profilins.