The basophil activation test (BAT) is a widely validated and reliable tool especially for the diagnosis of hymenoptera venom allergy. Nevertheless, several pitfalls have to be considered and outcomes ...may differ because of diverse in-house protocols and commercially available kits. We aimed to identify the factors that may influence results of the CD63-based BAT. Basophil responses to monoclonal anti-IgE (clone E124.2.8) and bee and wasp venom were determined by BAT based on CD63. The effect of stimulating factors such as, IL-3, cytochalasin B and prewarming of the samples was investigated. Furthermore, we compared two different flow cytometer systems and evaluated the influence of storage time, different staining protocols and anti-allergic drugs on the test results. Interleukin-3 enhanced the reactivity of basophils at 300 pM, but not at 75 and 150 pM. Prewarming of samples and reagents did not affect basophil reactivity. CD63 expression assayed after storage time of up to 48 h showed that basophil reactivity already started to decline after 4 h. Basophils stained with HLA-DR-PC5 and CD123-PE antibodies gated as HLA-DRneg/CD123pos cells showed the highest reactivity. No effect on test outcomes was observed at therapeutic doses of dimetindene and desloratadine. Finally, slight differences in the percentage of activated basophils, depending on the cytometer system used, were found. Basophil activation test should be performed as early as possible after taking the blood sample, preferably within 4 h. In contrast to the skin test, BAT can be performed in patients undergoing treatment with antihistamines. For reasons of multiple influencing factors, BAT should be performed only at validated laboratories.
Clinical indications for allergen immunotherapy (AIT) in respiratory and Hymenoptera venom allergy are well established; however, clinical contraindications to AIT are not always well documented. ...There are some discrepancies when classifying clinical contraindications for different forms of AIT as ‘absolute’ or ‘relative’. EAACI Task Force on ‘Contraindications to AIT’ was created to evaluate and review current literature on clinical contraindications, and to update recommendations for both sublingual and subcutaneous AIT for respiratory and venom immunotherapy. An extensive review of the literature was performed on the use of AIT in asthma, autoimmune disorders, malignant neoplasias, cardiovascular diseases, acquired immunodeficiencies and other chronic diseases (including mental disorders), in patients treated with β‐blockers, ACE inhibitors or monoamine oxidase inhibitors, in children under 5 years of age, during pregnancy and in patients with poor compliance. Each topic was addressed by the following three questions: (1) Are there any negative effects of AIT on this concomitant condition/disease? (2) Are more frequent or more severe AIT‐related side‐effects expected? and (3) Is AIT expected to be less efficacious? The evidence, for the evaluation of these clinical conditions as contraindications, was limited, and most of the conclusions were based on case reports. Based on an extended literature research, recommendations for each medical condition assessed are provided. The final decision on the administration of AIT should be based on individual evaluation of any medical condition and a risk/benefit assessment for each patient.
Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food ...allergen immunotherapy (FA‐AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE‐mediated Food Allergy, aims to provide evidence‐based recommendations for active treatment of IgE‐mediated food allergy with FA‐AIT. Immunotherapy relies on the delivery of gradually increasing doses of specific allergen to increase the threshold of reaction while on therapy (also known as desensitization) and ultimately to achieve post‐discontinuation effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA‐AIT has most frequently been assessed: here, the allergen is either immediately swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall, trials have found substantial benefit for patients undergoing either OIT or SLIT with respect to efficacy during treatment, particularly for cow's milk, hen's egg, and peanut allergies. A benefit post‐discontinuation is also suggested, but not confirmed. Adverse events during FA‐AIT have been frequently reported, but few subjects discontinue FA‐AIT as a result of these. Taking into account the current evidence, FA‐AIT should only be performed in research centers or in clinical centers with an extensive experience in FA‐AIT. Patients and their families should be provided with information about the use of FA‐AIT for IgE‐mediated food allergy to allow them to make an informed decision about the therapy.
Normothermic machine perfusion (NMP) has emerged as an innovative organ preservation technique. Developing an understanding for the donor organ immune cell composition and its dynamic changes during ...NMP is essential. We aimed for a comprehensive characterization of immune cell (sub)populations, cell trafficking and cytokine release during liver NMP. Single-cell transcriptome profiling of human donor livers prior to, during NMP and after transplantation shows an abundance of CXC chemokine receptor 1
/2
(CXCR1
/CXCR2
) neutrophils, which significantly decreased during NMP. This is paralleled by a large efflux of passenger leukocytes with neutrophil predominance in the perfusate. During NMP, neutrophils shift from a pro-inflammatory state towards an aged/chronically activated/exhausted phenotype, while anti-inflammatory/tolerogenic monocytes/macrophages are increased. We herein describe the dynamics of the immune cell repertoire, phenotypic immune cell shifts and a dominance of neutrophils during liver NMP, which potentially contribute to the inflammatory response. Our findings may serve as resource to initiate future immune-interventional studies.
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•Electromagnetic, heat transfer and fluid dynamics coupled for MW heating simulation.•Dielectric properties of NaY zeolite measured as a function of temperature 298–623 K.•Temperature ...evolution and distribution results validated with experimental data.•Model predicts thermal runaway of zeolite under MW heating.
Three-dimensional mathematical model was developed for a rectangular TE10n microwave heating cavity system, working at 2.45 GHz. Energy/heat, momentum equations were solved together with Maxwell’s electromagnetic field equations using Comsol Multiphysics® simulation environment. The dielectric properties, ε' and ε'', of NaY zeolite (Si/Al = 2.5) were evaluated as a function of temperature. Considering these values, the microwave heating of a porous fixed-bed made of dry NaY zeolite was simulated. Electric field distribution, axial and radial temperature profiles and temperature evolution with time were obtained. The zeolite fixed bed was heated up to 180 °C in 5 min, with 30 W power. The fixed-bed temperature evolution under non-steady state conditions showed the same trend as the one observed experimentally with only an average deviation of 10.3%. The model was used to predict microwave heating of other materials improving energy efficiency of the microwave cavity. Furthermore, the developed model was able to predict thermal runaway for zeolites.
Thermal pathogen suppression in glasshouse horticulture by treatment with steam generated through combustion of fossil fuel will become progressively less desirable. Radio wave treatment could be an ...alternative. It has several advantages, the most notable is that it generates heat where it is needed in soil, so that it avoids heat losses and long process duration associated with heat transport. Radio wave treatment is a more dynamic and more complex process though, therefore more advanced development tools are needed to apply it effectively. To this end, this study describes the development of a framework for numerical simulation of this process to aid in the development of the radio wave treatment process. The modeling framework is Comsol Multiphysics in combination with Matlab, and the computational requirements are constrained to workstation grade hardware. Simulation results are presented to demonstrate the simulation.
Regulatory approaches for allergen immunotherapy (AIT) products and the availability of high‐quality AIT products are inherently linked to each other. While allergen products are available in many ...countries across the globe, their regulation is very heterogeneous. First, we describe the regulatory systems applicable for AIT products in the European Union (EU) and in the United States (US). For Europe, a depiction of the different types of relevant procedures, as well as the committees involved, is provided and the fundamental role of national agencies of the EU member states in this complex and unique network is highlighted. Furthermore, the regulatory agencies from Australia, Canada, Japan, Russia, and Switzerland provided information on the system implemented in their countries for the regulation of allergen products. While AIT products are commonly classified as biological medicinal products, they are made available by varying types of procedures, most commonly either by obtaining a marketing authorization or by being distributed as named patient products. Exemptions from marketing authorizations in exceptional cases, as well as import of allergen products from other countries, are additional tools applied by countries to ensure availability of needed AIT products. Several challenges for AIT products are apparent from this analysis and will require further consideration.
Background
The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines on Allergen Immunotherapy (AIT) for the management of insect venom ...allergy. To inform this process, we sought to assess the effectiveness, cost‐effectiveness and safety of AIT in the management of insect venom allergy.
Methods
We undertook a systematic review, which involved searching 15 international biomedical databases for published and unpublished evidence. Studies were independently screened and critically appraised using established instruments. Data were descriptively summarized and, where possible, meta‐analysed.
Results
Our searches identified a total of 16 950 potentially eligible studies; of which, 17 satisfied our inclusion criteria. The available evidence was limited both in volume and in quality, but suggested that venom immunotherapy (VIT) could substantially reduce the risk of subsequent severe systemic sting reactions (OR = 0.08, 95% CI 0.03–0.26); meta‐analysis showed that it also improved disease‐specific quality of life (risk difference = 1.41, 95% CI 1.04–1.79). Adverse effects were experienced in both the build‐up and maintenance phases, but most were mild with no fatalities being reported. The very limited evidence found on modelling cost‐effectiveness suggested that VIT was likely to be cost‐effective in those at high risk of repeated systemic sting reactions and/or impaired quality of life.
Conclusions
The limited available evidence suggested that VIT is effective in reducing severe subsequent systemic sting reactions and in improving disease‐specific quality of life. VIT proved to be safe and no fatalities were recorded in the studies included in this review. The cost‐effectiveness of VIT needs to be established.
Adequate quality is essential for any medicinal product to be eligible for marketing. Quality includes verification of the identity, content and purity of a medicinal product in combination with a ...specified production process and its control. Allergen products derived from natural sources require particular considerations to ensure adequate quality. Here, we describe key aspects of the documentation on manufacturing and quality aspects for allergen immunotherapy products in the European Union and the United States. In some key parts, requirements in these areas are harmonized while other fields are regulated separately between both regions. Essential differences are found in the use of Reference Preparations, or the requirement to apply standardized assays for potency determination. As the types of products available are different in specific regions, regulatory guidance for such products may also be available in one specific region only, such as for allergoids in the European Union. Region‐specific issues and priorities are a result of this. As allergen products derived from natural sources are inherently variable in their qualitative and quantitative composition, these products present special challenges to balance the variability and ensuring batch‐to‐batch consistency. Advancements in scientific knowledge on specific allergens and their role in allergic disease will consequentially find representation in future regulatory guidelines.
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