Search

In this review, we report on relevant current topics in allergen immunotherapy (AIT) which were broadly discussed during the first Aarhus Immunotherapy Symposium (Aarhus, Denmark) in December 2015 by leading clinicians, scientists and industry representatives in the field. The aim of this symposium was to highlight AIT-related aspects of public health, clinical efficacy evaluation, mechanisms, development of new biomarkers and an overview of novel therapeutic approaches. Allergy is a public health issue of high socioeconomic relevance, and development of evidence-based action plans to address allergy as a public health issue ought to be on national and regional agendas. The underlying mechanisms are in the focus of current research that lays the ground for innovative therapies. Standardization and harmonization of clinical endpoints in AIT trials as well as current knowledge about potential biomarkers have substantiated proof of effectiveness of this disease-modifying therapeutic option. Novel treatments such as peptide immunotherapy, intralymphatic immunotherapy and use of recombinant allergens herald a new age in which AIT may address treatment of allergy as a public health issue by reaching a large fraction of patients., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In the European Union (EU), allergens used for diagnostic tests (TAs) are defined as medicinal products and have to be registered by national authorities. The current situation is not homogeneous. Existing authorizations need to be kept in the market in some EU states, while others need complete new authorizations requiring clinical trials, quality assurance methods, stability studies, and periodic safety update reports. Allergen manufacturers argue that offering a comprehensive panel of TAs may be economically disastrous. Expenses for initiation and maintenance of TA authorizations far exceed their related revenues and manufacturers may be forced to significantly limit their allergen portfolios. The availability of a wide range of high-quality TAs is very important for in vivo diagnoses of IgE-mediated allergies. Increased regulatory demands induce costs that need to be covered by public health organizations or reimbursed by health insurance companies., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In patients with allergic rhinitis (AR), the nasal provocation test (NPT) is the standard procedure to evaluate the clinical response of the nasal mucosa to allergens with a high specificity and sensitivity. In AR, it is the only test that really measures the response of the diseased mucosa to allergens while skin prick test and serum IgE confirm the clinical suspicion of sensitization. Moreover, it is of special relevance in the detection of patients with Local Allergic Rhinitis (LAR), where general sensitization cannot be measured. For the evaluation of therapeutic interventions, NPT has been used for the clinical monitoring of antiallergic drugs and allergen specific immunotherapy. Legislation within the European Union (EU) defines allergens used for diagnostic tests like NPT to be medicinal products according to Directive 2001/83 EC, but national law is considering these products to be medicinal devices in a number of EU countries. Thus, NPT products are governed by different legislations and therefore standards throughout the EU. In consequence, allergens used for diagnostic purposes need different registrations and Marketing Authorization by national authorities. After a transition period, regulations of EU Directives are to be implemented in national law by all member states. At the moment, most EU countries have not fully implemented these Directives, however, it can be expected that most countries will implement it and enforce their rules within the next years. This development has a tremendous impact on the availability of diagnostic allergens for NPT in Europe and will make make nasal provocation testing very difficult if not impossible. We describe the current situation of diagnostic allergens under the special legislative conditions in the EU with special focus on allergen products used for NPT and the consequences for the diagnosis of AR and LAR.

Abstract: In the European Union (EU), the regulatory framework regarding diagnostic allergen extracts is currently in the process of being implemented at the national level. Due to these regulations, the initial and periodic renewal expenses for the registration of diagnostic allergen extracts may render extract production unprofitable. Consequently, many extracts may be at risk of removal from the market. The current survey, which was conducted by a task force of the European Academy of Allergy and Clinical Immunology, aimed to assess the current practice of allergy diagnosis in Europe. This survey revealed that skin tests continue to be the main diagnostic procedure and are used as the first option in almost two‐third of all types of allergic diseases and in 90% of individuals suffering from respiratory allergies. Therefore, there is a need to ensure the availability of high‐quality allergen extracts to maintain the common diagnostic procedures used by EU professionals. To reach this goal, it is necessary to align efforts and establish active partnerships between manufacturers, relevant scientific societies, consumer organizations and authorities to maintain the availability of these diagnostic tools. [ABSTRACT FROM AUTHOR]

Background Sequential allergen desensitization provides temporary tolerance for allergic patients. We adapted a clinical protocol to desensitize human blood basophils ex vivo and investigated the mechanism and allergen specificity. Methods We included 28 adult, grass allergic subjects. The optimal, activating allergen concentration was determined by measuring activated CD63+ CD193+SSLow basophils in a basophil activation test with 8 log-dilutions of grass allergen. Basophils in whole blood were desensitized by incubation with twofold to 2.5-fold increasing allergen doses in 10 steps starting at 1 : 1000 of the optimal dose. Involvement of p38 mitogen-activated protein kinase ( MAPK) was assessed after 3 min of allergen stimulation ( n = 7). Allergen specificity was investigated by desensitizing cells from multi-allergic subjects with grass allergen and challenging with optimal doses of grass, birch, recombinant house dust mite (rDer p2) allergen or anti-IgE ( n = 10). Results Desensitization reduced the fraction of blood basophils responding to challenge with an optimal allergen dose from a median ( IQR) 81.0% (66.3-88.8) to 35.4% (19.8-47.1, P < 0.0001). CD63 MFI expression was reduced from 68 248 (29 336-92 001) to 30 496 (14 046-46 179, P < 0.0001). Basophils from multi-allergic subjects were desensitized with grass allergen. Challenge with grass allergen resulted in 39.6% activation (15.8-58.3). An unrelated challenge (birch, rDer p2 or anti-IgE) resulted in 53.4% activation (30.8-66.8, P = 0.16 compared with grass). Desensitization reduced p38 MAPK phosphorylation from a median 48.1% (15.6-92.8) to 26.1% (7.4-71.2, P = 0.047) and correlated with decrease in CD63 upregulation ( n = 7, r > 0.79, P < 0.05). Conclusion Desensitization attenuated basophil response rapidly and non-specifically at a stage before p38 MAPK phosphorylation. [ABSTRACT FROM AUTHOR]