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Purpose of review In the recent years, more cases of poultry meat allergy, both IgE- or non-IgE-mediated, are being reported. Patients have varied clinical reactivity at various levels of sensitivity to different meat preparations. The lack of validated biomarkers renders accurate diagnosis challenging. In this review, we aim to provide an overview of the current status of poultry meat allergy along with a description on the allergens implicated. Recent findings Poultry meat allergy occurs as a result of cross-reactions with known allergens of egg yolk or bird feathers or as genuine IgE-mediated sensitivity to allergens in poultry meat. Individuals can also develop non-IgE-mediated hypersensitivity reactions to poultry meat. Chicken serum albumin is the main responsible allergen in secondary cases, while myosin light chain, α parvalbumin, enolase, aldolase, hemoglobin, and α-actin have been recognized as potential eliciting allergens in genuine poultry meat allergy. Summary There is a wide phenotypic variation among patients with poultry meat allergy, regarding clinical severity and cross-reactivity features. Recognizing the various clinical entities of reactions to poultry meat is an important step towards accurate diagnosis and providing management options that are well received by patients.

Food challenges carry a burden of safety, effort and resources. Clinical reactivity and presentation, such as thresholds and symptoms, are considered challenging to predict ex vivo.To identify changes of peripheral immune signatures during oral food challenges (OFC) that correlate with the clinical outcome in patients with peanut allergy (PA).Children with a positive (OFCPeripheral immune profiles correlated with OFC outcome. OFCWe showed that peripheral immune signatures reflected dynamics of clinical outcome during OFC with peanut. Those immune alterations hold promise as a basis for predictive OFC biomarker discovery to monitor disease outcome and therapy of PA.

Alergia; Anafilaxia; Asma Allergy; Anaphylaxis; Asthma Al·lèrgia; Anafilaxi; Asma 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.

Novel protein sources can represent a risk for allergic consumers. The aim of this study was to evaluate the allergenicity of cowpea (Vigna unguiculata), an increasingly consumed legume and potential new industrial food ingredient which may put legume-allergic patients at risk.Children with allergy to legumes associated to peanut (LP group: n = 13) or without peanut allergy (L group: n = 14) were recruited and sensitization to several legumes including cowpea was assessed by prick tests and detection of specific IgE (sIgE). Cowpea protein extract was analyzed by SDS-PAGE and immunoblotting, IgE-reactive spots were subjected to mass spectrometry. IgE-cross-reactivity between cowpea, pea, and peanut was determined using ELISA inhibition assays. Basophil activation tests were performed to evaluate sensitivity and reactivity of patient basophils toward legumes.Prick tests and sIgE levels to cowpea were positive in 8/14 and 4/13 patients of the L group and in 9/13 and 10/13 patients of the LP group, respectively. Four major IgE-binding proteins were identified as vicilins and seed albumin. Cowpea extract and its vicilin fraction strongly inhibited IgE-binding to pea and peanut extract. Peanut, lentil, and pea were the strongest activators of basophils, followed by cowpea, soybean, mung bean, and lupin.A majority of patients with legume allergy were sensitized to cowpea proteins. Four novel allergens were identified in cowpea, among which storage proteins were playing an important role in IgE-cross-reactivity, exposing legume-allergic patients to the risk of clinical cross-reactivity to cowpea and thus adding cowpea to the group of nonpriority legumes that are not subjected to allergen labeling such as chickpea, pea, and lentil.

A cook's mate working in an Austrian restaurant reported acutely occurring urticarial skin lesions after processing and cooking squid. The prick-to-prick test with squid showed a ++ positive urticarial reaction. Elevated specific IgE antibody levels to squid, shrimp, and house dust mites as well as to tropomyosin from shrimp and house dust mite could be detected in the ImmunoCAP. By means of immunoblot and ELISA, a reaction to squid extract as well as increased IgE antibody levels to squid and tropomyosin from squid could be detected. The patient was diagnosed with a clinically and occupationally relevant type I allergy to squid with cross-reaction to tropomyosin of other invertebrates and therefore recognized as an occupational disease.

Although recent studies indicated that many fish-allergic patients may safely consume certain fish species, no clinical guidelines are available for identification of the exact species tolerated by specific patients.To investigate whether multiplex immunoglobulin E (IgE) testing reveals potentially tolerated fish through absence of IgE to parvalbumin (PV) and extracts from specific species.Sera from 263 clinically well-defined fish-allergic patients from Austria, China, Denmark, Luxembourg, Norway, and Spain were used in a research version of the ALEXUp to 38% of the patients were negative to cod PV, the most commonly used molecule in fish allergy diagnosis. Forty-five patients (17%) tested negative to PVs but positive to the respective fish extracts, underlining the requirement for extracts for accurate diagnosis. Between 60% (Spain) and 90% (Luxembourg) of the patients were negative to PV and extracts from ray, a cartilaginous fish, indicating its potential tolerance. Up to 21% of the patients were negative to at least 1 bony fish species. Of the species analyzed, negativity to mackerel emerged as the best predictive marker of negativity to additional bony fish, such as herring and swordfish.Parvalbumins and extracts from multiple fish species relevant for consumption should be used in fish-allergy diagnosis, which may help identify potentially tolerated species for individual patients.

The prevalence of food allergies has reached epidemic levels but the cause remains largely unknown. We discuss the clinical relevance of the gut mucosal barrier as a site for allergic sensitization to food. In this context, we focus on an important but overlooked part of the mucosal barrier in pathogenesis, the glycoprotein-rich mucus layer, and call attention to both beneficial and detrimental aspects of mucus–gut microbiome interactions. Studying the intricate links between the mucus barrier, the associated bacteria, and the mucosal immune system may advance our understanding of the mechanisms and inform prevention and treatment strategies in food allergy.

Polcalcins are important respiratory panallergens, whose IgE-binding capacity depends on the presence of calcium. Since specific immunotherapy is not yet available for the treatment of polcalcin-sensitized patients, we aimed to develop a molecule for efficient and safe immunotherapy. We generated a hypoallergenic variant of the grass pollen polcalcin Phl p 7 by introducing specific point mutations into the allergen’s calcium-binding regions. We thereby followed a mutation strategy that had previously resulted in a hypoallergenic mutant of a calcium-binding food allergen, the major fish allergen parvalbumin. Dot blot assays performed with sera from Phl p 7-sensitized patients showed a drastically reduced IgE reactivity of the Phl p 7 mutant in comparison to wildtype Phl p 7, and basophil activation assays indicated a significantly reduced allergenic activity. Rabbit IgG directed against mutant rPhl p 7 blocked patients’ IgE binding to wildtype Phl p 7, indicating the mutant’s potential applicability for immunotherapy. Mass spectrometry and circular dichroism experiments showed that the mutant had lost the calcium-binding capacity, but still represented a folded protein. In silico analyses revealed that the hypoallergenicity might be due to fewer negative charges on the molecule’s surface and an increased molecular flexibility. We thus generated a hypoallergenic Phl p 7 variant that could be used for immunotherapy of polcalcin-sensitized individuals.

This review searched for published evidence that could explain how different physicochemical properties impact on the allergenicity of food proteins and if their effects would follow specific patterns among distinct protein families. Owing to the amount and complexity of the collected information, this literature overview was divided in two articles, the current one dedicated to protein families of plant allergens and a second one focused on animal allergens. Our extensive analysis of the available literature revealed that physicochemical characteristics had consistent effects on protein allergenicity for allergens belonging to the same protein family. For example, protein aggregation contributes to increased allergenicity of 2S albumins, while for legumins and cereal prolamins, the same phenomenon leads to a reduction. Molecular stability, related to structural resistance to heat and proteolysis, was identified as the most common feature promoting plant protein allergenicity, although it fails to explain the potency of some unstable allergens (e.g. pollen-related food allergens). Furthermore, data on physicochemical characteristics translating into clinical effects are limited, mainly because most studies are focused on in vitro IgE binding. Clinical data assessing how these parameters affect the development and clinical manifestation of allergies is minimal, with only few reports evaluating the sensitising capacity of modified proteins (addressing different physicochemical properties) in murine allergy models. In vivo testing of modified pure proteins by SPT or DBPCFC is scarce. At this stage, a systematic approach to link the physicochemical properties with clinical plant allergenicity in real-life scenarios is still missing., The authors highly appreciate the support from the European Cooperation in Science and Technology (COST) Office. This article is based upon work from COST Action FA1402, supported by COST (www.cost.eu). This work was also supported by Fundação para a Ciência e Tecnologia under the Partnership Agreement UIDB 50006/2020 and by the projects AlleRiskAssess - PTDC/BAA-AGR/31720/2017 and NORTE-01-0145-FEDER-00001. C.V. is grateful to FCT grants (PD/BD/114576/2016) financed by POPH-QREN (subsidised by FSE and MCTES). T.C.V. is grateful to the Ministry of Education, Science and Technological Development of the Republic of Serbia through grant number OI172024. P.M.R. and D.S. are grateful to FCT through project UIDB/04326/2020 and Mar2020 16–02-01-FMP-0014 – ‘ALLYFISH’. J.K. and A.K. acknowledge the PRIDE program grant (PRIDE/11012546/NEXTIMMUNE) by the Fonds National de la Recherche (FNR), Luxembourg and a translational grant (APSIS, PMC/2017/02) by the Personalised Medicine Consortium (PMC), Luxembourg.

The relatively easy access to fish worldwide, alongside the increase of aquaculture production contributes to increased fish consumption which result in higher prevalence of respective allergies. Allergies to fish constitute a significant concern worldwide. beta-parvalbumin is the main elicitor for IgE-mediated reactions. Creatine, involved in the muscle energy metabolism, and ethylenediamine tetraacetic acid (EDTA), a calcium chelator, are potential molecules to modulate parvalbumin. The purpose of this study was to test creatine (2, 5 and 8%) and EDTA (1.5, 3 and 4.5%) supplementation in fish diets to modulate beta-parvalbumin expression and structure and its allergenicity in farmed European seabass (Dicentrarchus labrax) while assessing its effects on the end-product quality. Fish welfare and muscle quality parameters were evaluated by plasma metabolites, rigor mortis, muscle pH and sensory and texture analysis. Proteomics was used to assess alterations in muscle proteome profile and metabolic fingerprinting by Fourier transform infrared spectroscopy was used to assess the liver metabolic profile. In addition, IgE-reactivity to parvalbumin was analysed using fish allergic patient sera. Metabolic fingerprinting of liver tissue revealed no major alterations in infrared spectra with creatine supplementation, while with EDTA, only absorption bands characteristic of lipids were altered. Comparative proteomics showed up regulation of (tropo) myosin and phosphoglycerate mutase 2 with Creatine supplementation. In the case of EDTA proteomics showed up regulation of proteins involved in cellular and ion homeostasis. Allergenicity seems not to be modulated with creatine or EDTA supplementation as no decreased expression levels were found and IgE-binding reactivity showed no quantitative differences. info:eu-repo/semantics/publishedVersion

Food allergy is a collective term for several immune-mediated responses to food. IgE-mediated food allergy is the best-known subtype. The patients present with a marked diversity of clinical profiles including symptomatic manifestations, threshold reactivity and reaction kinetics. In-vitro predictors of these clinical phenotypes are evasive and considered as knowledge gaps in food allergy diagnosis and risk management. Peanut allergy is a relevant disease model where pioneer discoveries were made in diagnosis, immunotherapy and prevention. This review provides an overview on the immune basis for phenotype variations in peanut-allergic individuals, in the light of future patient stratification along emerging omic-areas. Beyond specific IgE-signatures and basophil reactivity profiles with established correlation to clinical outcome, allergenomics, mass spectrometric resolution of peripheral allergen tracing, might be a fundamental approach to understand disease pathophysiology underlying biomarker discovery. Deep immune phenotyping is thought to reveal differential cell responses but also, gene expression and gene methylation profiles (eg, peanut severity genes) are promising areas for biomarker research. Finally, the study of microbiome-host interactions with a focus on the immune system modulation might hold the key to understand tissue-specific responses and symptoms. The immune mechanism underlying acute food-allergic events remains elusive until today. Deciphering this immunological response shall enable to identify novel biomarker for stratification of patients into reaction endotypes. The availability of powerful multi-omics technologies, together with integrated data analysis, network-based approaches and unbiased machine learning holds out the prospect of providing clinically useful biomarkers or biomarker signatures being predictive for reaction phenotypes.

Background In the verge of getting a greater understanding of fish welfare, sensitive technological tools, such as proteomics, may assist the aquaculture industry as it allows an unbiased approach for the discovery of potential biomarkers for stress monitoring. Stress is characterized by a cascade of physiological responses that end-up inducing further changes at the whole-animal level that might either increase fitness or impair welfare. Monitorization of this dynamic process, up till now relies on indicators that are only a snapshot of the stress level experienced. Within this scope, using gilthead seabream ( Sparus aurata ) as a model, three chronic stress conditions, namely overcrowding, handling and hypoxia, were employed to evaluate the potential of the fish protein-based adaptations as reliable signatures of chronic stress, in contrast with the commonly used indicators of primary and secondary stress responses.Results A large spectrum of biological variation regarding cortisol and glucose levels was observed, which values rose higher in net handled fish. In this sense, a potential pattern of stressor-specificity was evidenced since the magnitude of response and tolerance varied markedly from a permanent (crowding) to a repetitive stressor (handling). Gel-based proteomics analysis of the plasma proteome also revealed that net handled fish had the highest number of proteins with significantly altered abundance, compared to the other trials, whereas mass spectrometric analysis, followed by gene ontology enrichment and protein-protein interaction analyses, characterized those as humoral components of the innate immune system and key elements on the response to stimulus.Conclusions Overall, this study represents the first screening of more reliable signatures of physiological adaptation to chronic stress in fish, allowing the future development of novel biomarker models to monitor fish welfare.

Background: Novel foods may provide new protein sources for a growing world population but entail risks of unexpected food-allergic reactions. No guidance on allergenicity assessment of novel foods exists, while for genetically modified (GM) crops it includes comparison of sequence identity with known allergens, digestibility tests and IgE serum screening. Objective: As a proof of concept, to evaluate non-/allergenic tropomyosins (TMs) regarding their potential as new calibrator proteins in functional biological in vitro assays for the semi-quantitative allergy risk assessment of novel TM-containing animal foods with mealworm TM as an example. Methods: Purified TMs (shrimp, Penaeus monodon; chicken Gallus gallus; E coli overexpression) were compared by protein sequencing, circular dichroism analysis and in vitro digestion. IgE binding was quantified using shrimp-allergic patients' sera (ELISA). Biological activities were investigated (skin testing; titrated basophil activation tests, BAT), compared to titrated biological mediator release using humanized rat basophil leukaemia (RBL) cells. Results: Shrimp and chicken TMs showed high sequence homology, both alpha-helical structures and thermal stability. Shrimp TM was stable during in vitro gastric digestion, chicken TM degraded quickly. Both TMs bound specific IgE from shrimp-allergic patients (significantly higher for shrimp TM), whereas skin reactivity was mostly positive with only shrimp TM. BAT and RBL cell assays were positive with shrimp and chicken TM, although at up to 100- to 1000-times lower allergen concentrations for shrimp than chicken TM. In RBL cell assays using both TM as calibrators, an activation of effector cells by mealworm TM similar to that by shrimp TM confirmed the already reported high allergenic potency of mealworm TM as a novel protein source. Conclusions & clinical relevance: According to current GM crops' allergenicity assessment, non-allergenic chicken TM could falsely be considered an allergen on a weight-of-evidence approach. However, calibrating allergenic potency in functional BAT and RBL cell assays with clinically validated TMs allowed for semi-quantitative discrimination of novel food protein's allergenicity. With TM calibration as a proof of concept, similar systems of homologous protein might be developed to scale on an axis of allergenicity. © 2019 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.

Background: Fish is one of the most important, allergenic foods worldwide. Parvalbumin is the well characterized, major allergen in fish muscle. In this study, we developed a protein- and a DNA-based method for the sensitive detection and authentication of eight commonly consumed fishes in food and compared their applicability. Methods: Fish parvalbumins were purified. Polyclonal, anti-parvalbumin antibodies were raised in rabbits and mice. Protein extracts from food were analyzed by quantitative ELISA. Parvalbumin genes were cloned and sequenced for the design of parvalbumin gene-specific PCR-primers. DNA extracted from food was subjected to specific PCR. Results: Increasing parvalbumin contents were quantified by ELISA in fresh fish, in the order of tuna < mackerel < cod < salmon/trout < redfish < carp < herring. The parvalbumin content of processed fish was up to 67% lower than in fresh fish. In spiked food samples, 1 to 15 ppm fresh fish and 30 to 170 ppm processed fish were still detectable by ELISA. The eight fishes were identified by specific PCR using 0.2 to 10 ng fish DNA. PCRs detected still 3 ppm fresh fish and 30 to 150 ppm processed fish in spiked samples. Conclusions: Both the protein- and the DNA-based method have sufficient sensitivity to protect fish-allergic consumers. The ELISA allows allergen quantification, while the PCR identifies the fish present in the food. The detection limits of both methods vary depending on different factors. Both methods need to be carefully validated for each fish and fish product when used in detection assays.

Purpose of review Fish is a common elicitor of IgE-mediated food allergy. Fish includes a large variety of foods, in terms of species and food processing, with marked distinction in local diets around the globe. Fish-allergic patients present with phenotypic diversity and major differences in levels of clinical cross-reactivity, features that pose an important challenge for the clinical diagnosis and management. Recent findings Parvalbumin is the major fish allergen. However, a single molecule is not sufficient but several homologs, allergens different from parvalbumin and allergen extracts, are needed for IgE-based diagnosis. Summary Parvalbumin-specific IgE are markers for clinical cross-reactions. Added value is provided by IgE typing to parvalbumin homologs from distantly related fish. IgE cosensitization profiles (parvalbumin, enolase, aldolase) are referred as severity markers. The allergen panel seems to be not yet complete why fish extracts still play a crucial role inserum IgE analysis. Further clinical validation of a multiplex approach in molecular fish allergy diagnosis is needed for striving to avoid unnecessary food restrictions and in a further sense, improved patient care. Ministry of Research, Luxembourg (JK, AK), the PRIDE program grant (PRIDE/11012546/NEXTIMMUNE) ;Fonds National de la Recherche (FNR), Luxembourg (JK, AK) and the Personalized Medicine Consortium Luxembourg (JK, AK). This work received national funds through FCT - Foundation for Science and Technology through project UID/Multi/04326/2019. FCT PhD grant SFRH/BD/136319/2018. info:eu-repo/semantics/publishedVersion

Fish is one of the most common elicitors of food-allergic reactions worldwide. These reactions are triggered by the calcium-binding muscle protein beta-parvalbumin, which was shown to have reduced immunoglobulin E (IgE)-binding capacity upon calcium depletion. This work aimed to reduce gilthead seabream allergenicity using diets supplemented with a calcium chelator. Three experimental feeds were tested, differing in ethylenediaminetetraacetic acid (EDTA) supplementation, and its effects on muscle and parvalbumin's IgE-reactivity were analyzed. Chromatographic determination of EDTA showed no accumulation in the muscle and sensory results demonstrated that the lowest concentration did not affect fish quality as edible fish. Proteomics revealed one protein related to muscle contraction with significantly different relative abundance. Immunoblot assays performed with fish-allergic patients sera indicated a 50% reduction in IgE-reactivity upon EDTA presence. These preliminary results provide the basis for the further development of a non-GMO approach to modulate fish allergenicity and improve safety of aquaculture fish. project ALLYFISH [16-02-01-FMP-0014-ALLYFISH] FCT - Foundation for Science and TechnologyPortuguese Foundation for Science and Technology [UID/Multi/04326/2019] info:eu-repo/semantics/publishedVersion

Background Clinical reactions to bony fish species are common in patients with allergy to fish and are caused by parvalbumins of the β-lineage. Cartilaginous fish such as rays and sharks contain mainly α-parvalbumins and their allergenicity is not well understood. Objective To investigate the allergenicity of cartilaginous fish and their α-parvalbumins in individuals allergic to bony fish. Methods Sensitization to cod, salmon, and ray among patients allergic to cod, salmon, or both (n = 18) was explored by prick-to-prick testing. Clinical reactivity to ray was assessed in 11 patients by food challenges or clinical workup. IgE-binding to β-parvalbumins (cod, carp, salmon, barramundi, tilapia) and α-parvalbumins (ray, shark) was determined by IgE-ELISA. Basophil activation tests and skin prick tests were performed with β-parvalbumins from cod, carp, and salmon and α-parvalbumins from ray and shark. Results Tolerance of ray was observed in 10 of 11 patients. Prick-to-prick test reactions to ray were markedly lower than to bony fish (median wheal diameter 2 mm with ray vs 11 mm with cod and salmon). IgE to α-parvalbumins was lower (median, 0.1 kU/L for ray and shark) than to β-parvalbumins (median, ≥1.65 kU/L). Furthermore, α-parvalbumins demonstrated a significantly reduced basophil activation capacity compared with β-parvalbumins (eg, ray vs cod, P < .001; n = 18). Skin prick test further demonstrated lower reactivity to α-parvalbumins compared with β-parvalbumins. Conclusions Most patients allergic to bony fish tolerated ray, a cartilaginous fish, because of low allergenicity of its α-parvalbumin. A careful clinical workup and in vitro IgE-testing for cartilaginous fish will improve patient management and may introduce an alternative to bony fish into patients’ diet.

Hymenoptera venom allergy can cause severe anaphylaxis in untreated patients. Polistes dominula is an important elicitor of venom allergy in Southern Europe as well as in the United States. Due to its increased spreading to more moderate climate zones, Polistes venom allergy is likely to gain importance also in these areas. So far, only few allergens of Polistes dominula venom were identified as basis for component-resolved diagnostics. Therefore, this study aimed to broaden the available panel of important Polistes venom allergens. The 100 kDa allergen Pol d 3 was identified by mass spectrometry and found to be a dipeptidyl peptidase IV. Recombinantly produced Pol d 3 exhibited sIgE-reactivity with approximately 66% of Polistes venom-sensitized patients. Moreover, its clinical relevance was supported by the potent activation of basophils from allergic patients. Cross-reactivity with the dipeptidyl peptidases IV from honeybee and yellow jacket venom suggests the presence of exclusive as well as conserved IgE epitopes. The obtained data suggest a pivotal role of Pol d 3 as sensitizing component of Polistes venom, thus supporting its status as a major allergen of clinical relevance. Therefore, Pol d 3 might become a key element for proper diagnosis of Polistes venom allergy.

Food allergy is an adverse immunological reaction to allergens present in food. Up to 4% adults and 8% children are affected by food allergy. The increase in allergic diseases to food has led to the need for better diagnostics and more effective therapeutic approaches. This book describes the molecular biology and immunology of major food allergens, from laboratory based science to clinical immunology, encompassing novel characterisation and quantification methods, the application of recombinant food allergens in molecular diagnosis and the development of novel therapeutics. This book is the ideal reference tool for researchers, students and allergy clinicians to accurately diagnose and manage food allergies.

Purpose of Review Allergen extracts are still widely used in allergy diagnosis as they are regarded as sensitive screening tools despite the fact that they may lack some minor allergens. Another drawback of extracts is their low specificity, which is due to the presence of cross-reactive allergens. Progress in allergen identification has disclosed a number of allergenic molecules of homologous sequence and structure which are present in different animal species. This review summarizes recent advances in mammalian and fish allergen identification and focuses on their clinical relevance. Recent Findings Serum albumins and parvalbumins are well-known animal panallergens. More recently several members of the lipocalin family were found to be cross-reactive between furry animals whereas in fish, additional allergens, enolase, aldolase and collagen, were found to be important and cross-reactive allergens. New epidemiological studies have analysed the prevalence and clinical relevance of mammalian and fish components. Summary Primary sensitization can be distinguished from cross-sensitization by using marker allergens. Although substantial progress has been made in allergen identification, only few markers are commercially available for routine clinical practice.

Availability of “exotic” foods is steadily increasing. In this report, we describe the first case of anaphylaxis to crocodile meat. The patient was a 13-year-old boy with severe immunoglobulin E–mediated allergy to chicken meat. When tasting crocodile meat for the first time, he developed an anaphylactic reaction. Cross-reactivity between chicken and crocodile meat was suspected to have triggered this reaction. Basophil activation and immunoglobulin E testing confirmed the boy’s allergic reaction to crocodile meat proteins. Molecular analysis identified a crocodile α-parvalbumin, with extensive sequence homology to chicken α-parvalbumin, as the main cross-reactive allergen. We conclude that crocodile meat can be a potent food allergen and patients with allergy to chicken meat should be advised to avoid intake of meat from crocodile species. Both foods and people travel around the world and accessibility to exotic foods is steadily growing. As a result, novel allergic cross-reactivities are likely to become a challenge in the management of food allergy and, as our report illustrates, cross-reactivity has to be considered even between foods that might not intuitively be perceived as related.

Although fish is an elementary component of a healthy diet, it is also a food with high allergenic potential. In most cases, allergic reactions are induced by parvalbumins – small, stable proteins found in the muscle tissue. Many parvalbumin-positive individuals present with clinical reactions to various fish species, which can be explained through cross-reacting IgE antibodies.

Resume L’allergie alimentaire concerne 1,4 a 3,7 % des adultes avec une preponderance feminine. Elle ne s’exprime que lorsque plusieurs facteurs sont reunis. Cet article analyse les donnees de la litterature. L’influence du climat, des expositions professionnelles, le role de l’exercice physique, de certains medicaments et des addictions est soulignee. Une sommation de plusieurs facteurs s’observe frequemment.

Arthropods form a broad phylum within the animal kingdom, comprising widely varying members such as insects, arachnids, crabs and centipedes. In addition to common allergies to house dust mites or hymenoptera venom, there are also rarer allergies that can be attributed to three major sources of allergens: cockroaches, ticks and storage mites. Other less known allergen sources include spiders, mosquitos, horseflies, red chironomid larvae, silverfish and ladybugs, as well as a variety of storage pests. At present, only extract-based test systems are available for the majority of allergens in IgE-based diagnostics. Molecular characterisation of numerous individual allergens has already been carried out. However, these individual allergens are only available for a small number of allergen sources (e. g. cockroaches and storage mites) in routine diagnostics. Particularly in the case of allergen sources with known high cross-reactivity, the use of marker allergens is believed to improve diagnostics. The currently known individual allergens of the above-mentioned allergy triggers from the arthropod realm are summarized and their potential use in allergy diagnostics discussed.

Gliederfuser sind ein umfangreicher Stamm des Tierreichs, zu dem sehr unterschiedliche Vertreter wie Insekten, Spinnentiere, Krebse oder Tausendfuser gehoren. Neben haufigen Allergien auf Hausstaubmilben oder Hymenopterengift gibt es seltenere Allergien, die sich auf drei Hauptallergenquellen zuruckfuhren lassen: Schaben, Zecken und Vorratsmilben. Weitere, weniger bekannte Allergenquellen sind Spinnen, Stechmucken, Pferdebremsen, die roten Larven der Zuckmucke, Silberfische, Marienkafer sowie verschiedene Vorratsschadlinge. Fur die IgE-basierte Diagnostik stehen fur die meisten Ausloser bisher nur extraktbasierte Testsysteme zur Verfugung. Die molekulare Charakterisierung einzelner Allergene ist in vielen Fallen bereits erfolgt. Diese Einzelallergene stehen jedoch nur fur wenige Allergenquellen (z. B. Schaben, Vorratsmilben) in der Routinediagnostik zur Verfugung. Besonders bei Allergenquellen, von denen eine hohe Kreuzreaktivitat bekannt ist, sollte der Einsatz von Markerallergenen eine Verbesserung der Diagnostik ermoglichen. Die aktuell bekannten Einzelallergene der o. g. Allergieausloser aus dem Reich der Gliederfuser werden zusammengefasst und der potenzielle Nutzen in der Allergiediagnostik diskutiert.

Resume Objectif de l’etude Le but de l’etude est de determiner la valeur ajoutee de l’etude du profil de sensibilisation moleculaire chez les patients allergiques au poisson. Patients et methodes Le diagnostic d’une allergie au poisson a ete retenu chez 62 patients sur la base d’une histoire clinique evocatrice, de tests cutanes et d’IgE specifiques positives aux extraits de poisson (cabillaud, saumon, thon). La determination des IgE specifiques vis-a-vis de la parvalbumine, de l’enolase, de l’aldolase et de la gelatine de poisson, quantifiees par Elisa, a ete realisee chez tous les patients. Resultats Quarante-cinq patients sont sensibilises a la parvalbumine. Chez les patients sensibilises a la parvalbumine de cabillaud (morue), 50 % sont egalement sensibilises a l’enolase et a l’aldolase. Chez les patients ayant des tests cutanes positifs au saumon et au thon (75,6 % et 67,6 % respectivement), des sensibilisations isolees a la parvalbumine ont ete observees. Une correlation positive est observee entre les taux moyens des IgE specifiques envers la parvalbumine et l’enolase de cabillaud, et la severite du tableau clinique, ce qui n’est pas le cas pour l’aldolase de cabillaud. Trois groupes de patients ont ete analyses selon leur degre de reactivite IgE envers la parvalbumine : un premier groupe ( n = 36) compose de patients sensibilises aux 3 poissons avec des symptomes moderes a severes. Les symptomes sont correles a la presence d’IgE au cabillaud (extrait total) et a la parvalbumine de cabillaud. Un second groupe est constitue de patients ( n = 9) monosensibilises et ayant une allergie de gravite mineure, principalement au saumon. Les symptomes sont correles a des IgE specifiques envers l’extrait de saumon et envers la parvalbumine de saumon. Le troisieme groupe est compose de patients ( n = 17) sensibilises a un nombre restreint de poissons et presentant des symptomes moderes a severes. Chez ces patients dont les IgE etaient negatives envers la parvalbumine, on objective la presence d’IgE a l’aldolase, l’enolase ou a la gelatine de poisson dans 70,6 % des cas. Danc ce dernier groupe, la presence d’IgE specifiques envers le cabillaud est rarement observee. Conclusion L’utilisation d’un panel d’allergenes moleculaires de poisson varies contribue a l’amelioration du diagnostic de l’allergie au poisson. Certains profils de sensibilisation semblent associes a des tableaux cliniques particuliers.

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.

BACKGROUND: Fish is one of the most allergenic foods. While clinical cross-reactivity among different fishes is a widely accepted feature of fish allergy, associations with other food allergies are not well understood. This study aims at analyzing the relevance of clinical cross-reactivity between fish and chicken meat in patients with allergy to chicken meat without sensitization to hen's eggs.METHODS: Patients with food allergy to fish and chicken meat (n = 29) or chicken meat only (n = 7) were recruited. IgE-reactive chicken proteins were identified (Edman, MS analysis) and quantified (ELISA). Allergens were used in IgE ELISA and skin testing.RESULTS: Chicken parvalbumin and two new allergens, aldolase and enolase, were identified at 12, 40, and 50 kDa, respectively. They were recognized by sIgE of 61%, 75%, and 83% of all patient sera which were in the majority of the cases positive for the fish homologues as well. Fish and chicken meat allergens were highly cross-reactive while high inhibition rates with fish or chicken allergens correlated with the patients' primary sensitization to fish or chicken. In cooked or roasted foods, enolase and aldolase were detectable in chicken breast while parvalbumin was detectable in chicken legs and wings.CONCLUSIONS: Fish and chicken meat are cross-reactive foods; both fish-allergic and chicken meat-allergic patients might be at risk of developing a food allergy to chicken meat or to fish, respectively. This clinical phenomenon is proposed to be termed 'fish-chicken syndrome' with cross-reactive allergens involved being parvalbumins, enolases, and aldolases.

Lipocalins represent the most important group of inhalant animal allergens. For some of them, three-dimensional protein structures have been resolved, but their functions are still elusive. Lipocalins generally display a low sequence identity between family members. The characterization of new lipocalin allergens has revealed however that some of them display a high sequence identity to lipocalins from another species. They constitute a new group of potentially cross-reactive molecules which, in addition to serum albumins, may contribute to allergic cross-reactions between animal dander of different species. However, the clinical relevance of cross-reactivity needs to be assessed. Further studies are needed to understand which of these animal lipocalins are the primary allergens and which are cross-reacting molecules. The use of single, well characterized allergens for diagnosis will allow the identification of the sensitizing animal, which is a prerequisite for specific immunotherapy.

Background: Although 95% of fish-allergic patients are sensitized to the major fish allergen parvalbumin, clinical reactions to different fish species vary considerably in symptoms, intensity and frequency in allergic subjects. This study aimed at the quantification of parvalbumin levels in salmon, trout, cod, carp, mackerel, herring, redfish and tuna. Methods: Fish muscle extracts were separated by SDS-PAGE and parvalbumin content was estimated by densitometric band quantification. Individual antisera were raised in BALB/c mice against parvalbumins purified from seven fish species. Parvalbumin content was quantified in fish (raw/processed) and skin prick test (SPT) solutions by ELISA using the corresponding anti-serum for detection and the purified parvalbumins as standards. Results: Using SDS-PAGE scanning, parvalbumin contents were 2 mg for cod, carp, redfish and herring. Using ELISA, parvalbumin content ranged from 2.5 mg per gram raw muscle for carp, herring and redfish. The parvalbumin content of processed samples (cooked/commercial) was 20–60% lower. Allergen content in SPT samples ranged from 20 to 70 µg parvalbumin/ml of extract. No parvalbumin was found in tuna SPT solution. Conclusion: The parvalbumin content of most commonly consumed fish species varies considerably. Differences range from severalfold to one hundredfold. This has to be taken into account when designing food challenge tests and advising fish-allergic patients.

Allergy to proteins and glycoproteins from animal sources is an important public health problem affecting both children and adults (1–3). Exposure to animal allergens is a key factor for the development of allergy, particularly for the development of allergic airway diseases such as asthma and rhinitis (4, 5). Among the many particles and molecules of animal origin present in our environment, some have the property to induce allergic sensitization and IgE-mediated reactions. Major animal allergens share common protein characteristics as they belong to specific protein families: a majority of inhalant mammalian allergens belong to the lipocalin and serum albumin families. Many mite allergens are proteases, food allergens are often EF-hand proteins, tropomyosins, or caseins (6–8). These protein family clusters observed in allergens suggest that common structural, biochemical, or functional features in addition to external adjuvant factors contribute to their allergenicity. The understanding of the nature their allergenicity is of high importance as it contributes to the development of future diagnostic tools and therapeutic strategies (9–12). The present compilation of review articles illustrates that animal allergens are ubiquitous. The human immune system is exposed to these proteins not only via the respiratory tract such as for pet and house dust mite allergens via the intestine such as for food and helminth allergens but also via the skin such as for insect allergens. The extensive review of Zahradnik and Raulf focuses on animal allergens from furry animals in indoor (cat, dog) and outdoor environment (horse, cattle). Allergies to these animal proteins are a public problem as exposure is not limited to the original source but as these molecules become airborne and are carried on clothing to public buildings, the general population is exposed to these allergens. Allergen detection in the private or occupational context is therefore an important first step to develop avoidance strategies for patients at risk. Diaz-Perales et al. present an overview of uncommon allergenic sources such as exotic pets, which are on the rise as elicitors of animal allergies. These sources are to be considered as relevant because on one hand, their numbers are progressively increasing in households and on the other hand, cross-reactivity to common companion animals via molecules of conserved protein families might occur. Hentges and colleagues approach the topic of animal allergens from another point of view by focusing on common features of the human immune response to three allergen families, namely, secretoglobins, lipocalins, and serum albumins. Mammalian allergens initiate a broad variety of immunological processes in sensitized patients. The understanding of these mechanisms is crucial for defining strategies of future immunotherapies. Dumez et al. refer to the most frequent animal elicitors of allergy, which are house dust mites. Among the spectrum of identified mite allergens, they focus on the allergens’ biological function in the context of activation pathways initiating the underlying immune response during sensitization. The answer to the crucial question “why is an allergen an allergen?” seems to be well advanced in this context. This highlights the need for such functional analysis for further animal allergens. Fitzsimmons, Falcone, and Dunne report on allergens from helminths, which provoke strongly skewed Th2 responses as a normal physiological response upon parasitic infection. This review touches another important aspect: a reduced allergy prevalence has been associated with helminth endemic areas. But on the other hand, many environmental animal allergens have homologs in metazoan parasites, which may lead to cross-reactivity and increase of allergy prevalence. As a perspective, further elucidation of the immunological processes during parasite infection may improve insights for the development of therapeutic strategies in allergy. Kuehn and colleagues target another important source of animal allergens from food origin, namely fish allergens, which enter the human body by ingestion, inhalation, or skin contact. Molecular and immunological characteristic of the major fish allergens, parvalbumins, as well as the recently described enolases and aldolases, are in the focus while highlighting the variable allergenicity of closely related isoallergens and providing a basis for further studies of the mechanism of sensitization and allergy. Spillner, Blank, and Jakob detail the recent rapid advances in the characterization of hymenoptera venom allergens. The availability of a substantial number of isolated and recombinant allergens allowed to define individual patient IgE-profiles, to predict cross-reactivity and clinical cross-sensitization. The use of an increasing molecular allergen panel will ultimately allow to monitor and assess therapeutic outcome. Salazar and Ghaemmaghami report on the role of dendritic and epithelial cells in the process of allergic sensitization. They focus on how different receptors such as C-type lectin, toll-like and protease activated receptors, and the associated signaling pathways contribute to the sensitization process. The elucidation of the molecular mechanisms of dendritic and epithelial cell cross-talk in the process of sensitization will hopefully lead to the development of new therapeutic applications. Van Hage and Pauli finally summarize the recent advances in immunotherapy for mammalian allergy. Most studies focused on Fel d 1, the major cat allergen, as it is a well characterized allergen in terms of B- and T-cell epitopes. Different molecular design strategies, the use of the molecules in mouse models as well as in clinical trials and therapeutic outcomes are presented. The field is evolving rapidly and further studies are needed to assess safety and efficacy of the new molecules. We are thankful to all colleagues who contributed to this Research Topic, without their highly valuable expertise in different fields of research on animal allergen research it would not have been possible to realize this issue.