Fish allergenicity modulation using tailored enriched diets—Where are we?

Food allergy is an abnormal immune response to specific proteins in a certain food. The chronicity, prevalence, and the potential fatality of food allergy, make it a serious socio-economic problem. Fish is considered the third most allergenic food in the world, affecting part of the world population with a higher incidence in children and adolescents. The main allergen in fish, responsible for the large majority of fish-allergic reactions in sensitized patients, is a small and stable calcium-binding muscle protein named beta-parvalbumin. Targeting the expression or/and the 3D conformation of this protein by adding specific molecules to fish diets has been the innovative strategy of some researchers in the fields of fish allergies and nutrition. This has shown promising results, namely when the apo-form of beta-parvalbumin is induced, leading in the case of gilthead seabream to a 50% reduction of IgE-reactivity in fish allergic patients.info:eu-repo/semantics/publishedVersio

Immune profiling the blood and the gut microbiome: Advanced population- and patient-based stratification for tackling the allergy epidemic

The global burden of allergic diseases is on the rise, calling for improved diagnostic, treatment and prevention strategies. To tackle this crisis and to promote novel solutions, a multitude of contributing factors requires consideration, ranging from a deeper understanding of the underlying disease mechanisms to a deeper understanding of the disease etiology. Both intrinsic, such as genetic predisposition, and extrinsic factors, such as environmental exposures and lifestyle, play significant roles in epithelial barrier disruption and shifts of the immune balance from tolerance to T helper 2 (Th2) immunity against usually harmless antigens. At the site of epithelial barrier disturbance, alterations in the microbiome composition and function, known as dysbiosis, emerged as further contributors to the development of allergic conditions. Taking into account those aspects, the primary objective of this PhD thesis was to investigate IgE-mediated allergies and explore innovative strategies for the categorization of entire populations as well as specific patient subgroups. The ultimate aim is to enhance patient care and well-being through these advancements. To establish a first knowledge base on allergies in Luxembourg, we examined an adult, cross-sectional population-based cohort (Study 1). This work employed a new integrated approach, using blood IgE signatures, as well as health and lifestyle determinates. We revealed important insights into the identification of high-risk individuals, facilitating potential targeted interventions and preventive measures. We saw a high burden in the youngest population, mostly with pollen allergies and related food allergies. Especially in food allergy, clinical heterogeneity is a well-recognized challenge, with wide variations observed for reaction thresholds, severity, and organs involved. A review of current literature identified gaps in peanut allergy diagnosis as a model for severe and persistent food allergies (Study 2). Current diagnostic measures have limitations in accurately predicting clinical reactivity, underscoring the need for advancements in this field to improve patient care and outcomes. Relating to this knowledge gap, we aimed to better stratify patients based on novel complex blood immune patterns (Study 3). Integrating immune cell changes during oral food challenge with clinical outcomes, patients with variable clinical reactivity differed based on unique immune cell profiles. Our results pointed even to immune patterns involving into reactions of the gastrointestinal tract, with the great potential as a predictive marker. Finally, in a novel field of patient classification, fecal immune factors were explored in food-allergic patients (Study 4). We succeeded to correlate clinical outcomes of established peanut allergy with characteristics of the gut microbiome and so far underexplored fecal markers, elevated IgE and Th17 cytokines. This innovative approach offers promising prospects for personalized management and treatment of allergic conditions, as well as an early disease marker potentially aiding in prevention. In conclusion, the findings of this PhD thesis provide important insights into the development of population-based and personalized approaches, paving the way for targeted interventions, improved diagnostic measures, and enhanced patient care in the field of allergic diseases.3. Good health and well-bein

Mammalian derived lipocalin and secretoglobin respiratory allergens strongly bind ligands with potentially immune modulating properties.

peer reviewedAllergens from furry animals frequently cause sensitization and respiratory allergic diseases. Most relevant mammalian respiratory allergens belong either to the protein family of lipocalins or secretoglobins. Their mechanism of sensitization remains largely unresolved. Mammalian lipocalin and secretoglobin allergens are associated with a function in chemical communication that involves abundant secretion into the environment, high stability and the ability to transport small volatile compounds. These properties are likely to contribute concomitantly to their allergenic potential. In this study, we aim to further elucidate the physiological function of lipocalin and secretoglobin allergens and link it to their sensitizing capacity, by analyzing their ligand-binding characteristics. We produced eight major mammalian respiratory allergens from four pet species in E.coli and compared their ligand-binding affinities to forty-nine ligands of different chemical classes by using a fluorescence-quenching assay. Furthermore, we solved the crystal-structure of the major guinea pig allergen Cav p 1, a typical lipocalin. Recombinant lipocalin and secretoglobin allergens are of high thermal stability with melting temperatures ranging from 65 to 90°C and strongly bind ligands with dissociation constants in the low micromolar range, particularly fatty acids, fatty alcohols and the terpene alcohol farnesol, that are associated with potential semiochemical and/or immune-modulating functions. Through the systematic screening of respiratory mammalian lipocalin and secretoglobin allergens with a large panel of potential ligands, we observed that total amino acid composition, as well as cavity shape and volume direct affinities to ligands of different chemical classes. Therefore, we were able to categorize lipocalin allergens over their ligand-binding profile into three sub-groups of a lipocalin clade that is associated with functions in chemical communication, thus strengthening the function of major mammalian respiratory allergens as semiochemical carriers. The promiscuous binding capability of hydrophobic ligands from environmental sources warrants further investigation regarding their impact on a molecule's allergenicity

IgE-mediated peanut allergy: Current and novel predictive biomarkers for clinical phenotypes using multi-omics approaches

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

Novel, computational IgE‐clustering in a population‐based cross‐sectional study: Mapping the allergy burden

Abstract Background Even though the prevalence of allergies is increasing, population‐based data are still scarce. As a read‐out for chronic inflammatory information, new methods are needed to integrate individual biological measurements and lifestyle parameters to mitigate the consequences and costs of allergic burden for society. Methods More than 480.000 data points were collected from 1462 Luxembourg adults during the representative, cross‐sectional European Health Examination Survey, spanning health and lifestyle reports. Deep IgE‐profiles based on unsupervised clustering were correlated with data of the health survey. Findings 42.6% of the participants reported a physician‐diagnosed allergy and 44% were found to be IgE‐positive to at least one allergen or extract. The main sensitization sources were tree pollens followed by grass pollens and mites (52.4%, 51.8% and 40.3% of sensitized participants respectively), suggesting seasonal as well as perennial burden. The youngest group of participants (25–34 years old) showed the highest burden of sensitization, with 18.2% of them having IgE to 10 or more allergen groups. Unsupervised clustering revealed that the biggest cluster of 24.4% of participants was also the one with the highest medical need, marked by their multi‐sensitization to respiratory sources. Interpretation Our novel approach to analyzing large biosample datasets together with health information allows the measurement of the chronic inflammatory disease burden in the general population and led to the identification of the most vulnerable groups in need of better medical care

EAACI Molecular Allergology User's Guide 2.0

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

EAACI Molecular Allergology User's Guide 2.0

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.Peer reviewe