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The significance of B‐cell memory in sustaining IgE‐mediated allergies but also ensuring the development of long‐term allergen tolerance has remained enigmatic. However, well‐thought murine and human studies have begun to shed more light on this highly disputed subject. The present mini review highlights important aspects, like the involvement of IgG1 memory B cells, the meaning of low‐ or high‐affinity IgE antibody production, the impact of allergen immunotherapy, or the relevance of local memory established by ectopic lymphoid structures. Based on recent findings, future investigations should lead to deeper knowledge and the development of improved therapies treating allergic individuals. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Heat‐and‐pepsin‐sensitive plant food allergens (PR‐10 and profilin) sometimes cause systemic reaction. Objective: To detect the risk factors for systemic reactions induced by labile food allergens. Methods: A retrospective multicenter study was performed on patients with a documented history of systemic allergic reaction to labile plant food allergens and on age‐matched controls with a history of oral allergy syndrome (OAS) induced by the same foods. Offending foods, their amount, and state (solid or liquid), and potential cofactors (nonsteroidal anti‐inflammatory drugs, protonic pump inhibitors, exercise, alcohol, and fasting) were considered. Results: We studied 89 patients and 81 controls. Sensitization to PR‐10 or profilin, IgE to Bet v 1 and/or Bet v 2, and foods causing OAS were similar in the two groups. Twenty patients experienced >1 systemic allergic reaction. Tree nuts, Rosaceae, Apiaceae, and soymilk were the main offending foods. Seventeen (19%) patients were taking a PPI when the systemic reaction occurred (vs 5% in controls; P <.025). The ingestion of the offending food in liquid form (soymilk) was frequent among patients (15%) but unusual among controls (2%; P <.025). Soy milk‐induced systemic reactions were independent of PPI treatment. Fasting and excess of allergen, but not NSAID and exercise, were other relevant cofactors for systemic reactions. Systemic reactions occurred without any identifiable cofactor in 39 (44%) cases. Conclusion: PR‐10‐ and profilin‐induced systemic reactions are facilitated by PPI, ingestion of large amounts of unprocessed foods, and fasting. Soybean beverages represent a risk for PR‐10 hypersensitive patients and should be avoided. [ABSTRACT FROM AUTHOR]

Allergic diseases are characterized by overactive type 2 immune responses to allergens and immunoglobulin E (IgE)‐mediated hypersensitivity. Emerging evidence suggests that follicular helper T (TFH) cells, rather than type 2 T‐helper (TH2) cells, play a crucial role in controlling IgE production. However, follicular regulatory T (TFR) cells, a specialized subset of regulatory T (TREG) cells resident in B‐cell follicles, restricts TFH cell‐mediated help in extrafollicular antibody production, germinal center (GC) formation, immunoglobulin affinity maturation, and long‐lived, high‐affinity plasma and memory B‐cell differentiation. In mouse models of allergic asthma and food allergy, CXCR5+ TFH cells, not CXCR5− conventional TH2 cells, are needed to support IgE production, otherwise exacerbated by CXCR5+ TFR cell deletion. Upregulation of TFH cell activities, including a skewing toward type 2 TFH (TFH2) and IL‐13 producing TFH (TFH13) phenotypes, and defects in TFR cells have been identified in patients with allergic diseases. Allergen immunotherapy (AIT) reinstates the balance between TFH and TFR cells in patients with allergic diseases, resulting in clinical benefits. Collectively, further understanding of TFH and TFR cells and their role in the immunopathogenesis of allergic diseases creates opportunities to develop novel therapeutic approaches. [ABSTRACT FROM AUTHOR]

Modern health care requires a proactive and individualized response to diseases, combining precision diagnosis and personalized treatment. Accordingly, the approach to patients with allergic diseases encompasses novel developments in the area of personalized medicine, disease phenotyping and endotyping, and the development and application of reliable biomarkers. A detailed clinical history and physical examination followed by the detection of IgE immunoreactivity against specific allergens still represents the state of the art. However, nowadays, further emphasis focuses on the optimization of diagnostic and therapeutic standards and a large number of studies have been investigating the biomarkers of allergic diseases, including asthma, atopic dermatitis, allergic rhinitis, food allergy, urticaria and anaphylaxis. Various biomarkers have been developed by omics technologies, some of which lead to a better classification of distinct phenotypes or endotypes. The introduction of biologicals to clinical practice increases the need for biomarkers for patient selection, prediction of outcomes and monitoring, to allow for an adequate choice of the duration of these costly and long‐lasting therapies. Escalating healthcare costs together with questions about the efficacy of the current management of allergic diseases require further development of a biomarker‐driven approach. Here, we review biomarkers in diagnosis and treatment of asthma, atopic dermatitis, allergic rhinitis, viral infections, chronic rhinosinusitis, food allergy, drug hypersensitivity and allergen immunotherapy with a special emphasis on specific IgE, the microbiome and the epithelial barrier. In addition, EAACI guidelines on biologicals are discussed within the perspective of biomarkers. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy for food allergy requires prolonged treatment protocols and, in most cases, does not lead to durable modulation of the allergic immune response. We have demonstrated an intranasal (IN) nanoemulsion adjuvant that redirects allergen‐specific Th2 responses toward Th1 and Th17 immunity, and protects from allergen challenge after only 2‐4 monthly administrations. Here, we investigate the ability of this technology to provide long‐term modulation of allergy in a murine model of cow's milk allergy. Methods: Six weeks after sensitization to bovine casein, mice received four, monthly IN immunizations with nanoemulsion formulated with casein. Protection from casein challenge was assessed at 4 and 16 weeks after the final vaccine administration. Results: The NE vaccine significantly blunted the physiological responses to allergen challenge, and this effect persisted for at least 16 weeks. The protection from challenge was associated with the suppression of casein‐specific Th2 immunity and induced Th1 and Th17 cytokines as well as induction of IL‐10. Of interest, while immunized animals showed significantly decreased Th2 cytokine responses, cow's milk‐specific IgE remained elevated in the serum at levels associated with reactivity in control sensitized animals. Protection was associated with suppressed mast cell activation and markedly reduced mast cell infiltration into the small intestine. Conclusion: The sustained unresponsiveness of at least 16 weeks after vaccination suggests that the nanoemulsion vaccine alters the allergic phenotype in a persistent manner different from traditional desensitization, and this leads to long‐term suppressive effects on allergic disease without eliminating serum IgE. [ABSTRACT FROM AUTHOR]

The majority of allergic diseases, including asthma, atopic dermatitis and food allergy, are caused by allergen-specific IgE production and Th2-polarized immune responses. Because of the central role Th2 immune responses play in the genesis of allergic disease, it is important to focus on therapeutic approaches capable of suppressing or redirecting these Th2 immune responses. NE immunization (D) reduces production of allergen-specific IgE while (E) increasing allergen-specific IgA and IgG2a antibodies. [Extracted from the article]

Background: In high‐risk populations, allergen‐specific prophylaxis could protect from sensitization and subsequent development of allergic disease. However, such treatment might itself induce sensitization and allergies, thus requiring hypoallergenic vaccine formulations. We here characterized the preventive potential of virus‐like nanoparticles (VNP) expressing surface‐exposed or shielded allergens. Methods: Full‐length major mugwort pollen allergen Art v 1 was selectively targeted either to the surface or to the inner side of the lipid bilayer envelope of VNP. Upon biochemical and immunological analysis, their preventive potential was determined in a humanized mouse model of mugwort pollen allergy. Results: Virus‐like nanoparticles expressing shielded version of Art v 1, in contrast to those expressing surface‐exposed Art v 1, were hypoallergenic as they hardly induced degranulation of rat basophil leukemia cells sensitized with Art v 1‐specific mouse or human IgE. Both VNP versions induced proliferation and cytokine production of allergen‐specific T cells in vitro. Upon intranasal application in mice, VNP expressing surface‐exposed but not shielded allergen induced allergen‐specific antibodies, including IgE. Notably, preventive treatment with VNP expressing shielded allergen‐protected mice from subsequent sensitization with mugwort pollen extract. Protection was associated with a Th1/Treg‐dominated cytokine response, increased Foxp3+ Treg numbers in lungs, and reduced lung resistance when compared to mice treated with empty particles. Conclusion: Virus‐like nanoparticles represent a novel and versatile platform for the in vivo delivery of allergens to selectively target T cells and prevent allergies without inducing allergic reactions or allergic sensitization. Allergen‐expressing VNP, which are produced in HEK 293T cells with the help of MoMLV structural proteins, are unable to stimulate allergen‐specific B cells or sensitized effector cells (basophils, mast cells). Instead, upon i.n. application, they are being taken up by lung‐resident CD103+ DC and alveolar macrophages, which unpack their (allergic) cargo, expand Foxp3+ Treg cells and prevent from sensitization. [ABSTRACT FROM AUTHOR]

Allergen‐specific immunotherapy, which is performed by subcutaneous injection or sublingual application of allergen extracts, represents an effective treatment against type I allergic diseases. However, due to the long duration and adverse reactions, only a minority of patients decides to undergo this treatment. Alternatively, early prophylactic intervention in young children has been proposed to stop the increase in patient numbers. Plasmid DNA and mRNA vaccines encoding allergens have been shown to induce T helper 1 as well as T regulatory responses, which modulate or counteract allergic T helper 2–biased reactions. With regard to prophylactic immunization, additional safety measurements are required. In contrast to crude extracts, genetic vaccines provide the allergen at high purity. Moreover, by targeting the encoded allergen to subcellular compartments for degradation, release of native allergen can be avoided. Due to inherent safety features, mRNA vaccines could be the candidates of choice for preventive allergy immunizations. The subtle priming of T helper 1 immunity induced by this vaccine type closely resembles responses of non‐allergic individuals and—by boosting via natural allergen exposure—could suffice for long‐term protection from type I allergy. [ABSTRACT FROM AUTHOR]

In the first of two papers we described the development in the field of allergy mechanisms as described by Clinical and Experimental Allergy in 2015. Experimental models of allergic disease, basic mechanisms, clinical mechanisms and allergens are all covered. A second paper will cover clinical aspects. [ABSTRACT FROM AUTHOR]

An author index for the European Academy of Allergy and Clinical Immunology (EAACI) 2016 is presented.