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Diagnosing immediate drug hypersensitivity reactions (IDHRs) can pose a significant challenge and there is an urgent need for safe and reliable tests. Evidence has emerged that the basophil activation test (BAT), an in vitro assay that mirrors the in vivo response, can be a complementary test for many drugs. In this position paper, members of Task Force (TF) "Basophil activation test in the evaluation of Drug Hypersensitivity Reactions" from the European Academy of Allergy and Clinical Immunology (EAACI) present the data from a survey about the use and utility of BAT in IDHRs in Europe. The survey results indicate that there is a great interest for using BAT especially for diagnosing IDHRs. However, there are still main needs, mainly in the standardization of the protocols. Subsequently consensus‐based recommendations were formulated for: (i) Technical aspects of BAT in IDHRs including type of sample, management of drugs, flow cytometry protocols, interpretation of the results; and (ii) Drug‐specific aspects that should be taken into account when performing BAT in relation to betalactams, neuromuscular blocking agents, fluoroquinolones, chlorhexidine, opioids, radio contrast media, chemotherapeutics, biological agents, nonsteroidal anti‐inflammatory drugs, COVID vaccine, and excipients. Moreover, aspects in the evaluation of pediatric population have also been considered. All this indicates that BAT offers the clinician and laboratory a complementary tool for a safe diagnostic for IDHRs, although its place in the diagnostic algorithm depends on the drug class and patient population (phenotype, geography, and age). The standardization of BAT is important for generalizing this method beyond the individual laboratory. [ABSTRACT FROM AUTHOR]

The article discusses the basophil activation test (BAT) as a diagnostic tool for managing patients with IgE-mediated allergies. The authors emphasize the need for standardization and external quality assurance (EQA) of laboratory protocols and results interpretation. A task force was created to develop a consensus protocol for BAT-EQA, and round robin tests were conducted to train participating laboratories. The article presents a proposed standard operating protocol for BAT and highlights the importance of EQA for routine implementation of the assay. The authors conclude that the consensus protocol provides acceptable inter- and intralaboratory variability and can be implemented across Europe. [Extracted from the article]

Diffusion of atoms or molecules (generally: particles) is driven by differences and gradients of the chemical potential of the particles in their accessible space. If the difference of the chemical potential is due to differences of concentrations alone, one arrives at the diffusion equations of Fick. The diffusion coefficients are described in known models by vibrations of atoms in condensed matter which cause the exchange of preferentially neutral particles with neighbouring particles, impurities, interstitial places and vacancies near or on surfaces, grain boundaries, dislocation lines and in the homogeneous bulk. The rates of electronic transitions, however, increase also in melts and solids of chemically bonded particles with increasing temperature. Such transitions cause large fluctuating deviations of the local energy, the charge distribution and the local chemical and electrical potentials. The fluctuating deviations interact with the core ions and drive particles to interchange. This mechanism that supplements the known mechanisms of diffusion has not yet found adequate attention in the literature until now. Foundations, experimental results, evidence and consequences for diffusion are discussed. [ABSTRACT FROM AUTHOR]

Milestones in the development of thermodynamics are the discovery of the absolute temperature scale and the recognition that differential "heat" is a form of energy given as the product of absolute temperature and differential entropy. Following a new path, the last statement results from a careful analysis of the heat transfer applying the first theorem without reference to the usual cycles in thermodynamics. This confirms also characteristic properties of entropy. In particular, the total entropy can never decrease in a process. In thermal equilibrium, the differential thermal energy is proportional to the differential entropy with the constant of proportionality being the temperature of the heat and entropy. Hence, thermal energy and entropy are transferred simultaneously into the same storage facilities, some of which are mentioned. However, the issue which one is the superior quantity is obsolete. The entropy is maximum for a given amount of exchanged thermal energy and, vice versa, for a given amount of exchanged entropy the concomitant energy is minimum. We calculate the thermal energy and entropy of phonons (as bosons) in oscillators and of electrons (as fermions) in their states of solids and melts as examples from statistical thermodynamics. The thermal energy or heat is the sum of the energies of all bosons and fermions in their elementary states or quantum states according to Bose Einstein and Fermi Dirac statistics in thermal equilibrium minus the total energy in the limit T→0 K. The entropy can be written as mixing entropy of all of these quantum states weighted with their occupancies, in agreement with an earlier publication. Thus, entropy is a logarithmic metrics of the number of all possible variants to distribute the respective total energy over all elementary states in thermal equilibrium. [ABSTRACT FROM AUTHOR]

Abstract: The viscosity of fluids and melts is an important characteristic to steer processes and reactions of materials, to use lubricants and to fabricate diverse products of glass. To steer such fabrication processes reliably and free of failures one necessarily needs to understand and use the true data of the viscosity. The forces applied to measure the viscosity act also to accelerate parts of the samples and particularly to deform them elastically. To evaluate the viscosity one must necessarily consider such ‘side reactions’. Cylindrical samples under longitudinal deformation are demonstrated to deform rather elastically than by viscous flow upon application of the load, e. g. Neglecting this effect the ’viscosity’ apparently decreasing with increasing load may be misinterpreted as non‐Newtonian viscosity. In fact, it represents the change from viscous to elastic behaviour with decreasing time interval of the application of force. Furthermore, production of entropy during deformation for measurement has to be taken into account adequately. The sample warms up during heavy deformation. If the viscosity depends strongly on the temperature, one must take into account that temperature and viscosity change with the intensity of the load. Then the so called ’shear thinning’ is rather ’sheer heating’. This is demonstrated quantitatively with data of the viscosity as a function of the load, which have recently been published using capillary rheometers. [ABSTRACT FROM AUTHOR]

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]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Prenatal exposures to persistent organic pollutants ( POPs) have been associated with asthma medication use and self-reported symptoms, but associations with lung function and allergic sensitization have been minimally explored. The aim of the study was to examine the associations between prenatal exposures to POPs and allergic sensitization and lung function in 20-year-old offspring. Methods In a Danish cohort of 965 pregnant women established in 1988-1989, six polychlorinated biphenyl ( PCB) congeners, hexachlorobenzene ( HCB), and dichlorodiphenyldichloroethylene (p,p'- DDE) were quantified in archived maternal serum drawn in gestational week 30 ( n = 872). Among those with available maternal exposure information, at age 20, 421 offspring attended attended a clinical examination including measurements of allergic sensitization (serum-specific IgE ≥ 0.35 kUA/L) (n = 418) and lung function [forced expiratory volume in one second ( FEV1) and forced vital capacity ( FVC)] (n = 414). Results There were no associations between maternal concentrations of POPs and offspring allergic sensitization at 20 years of age. Maternal concentrations of POPs were, however, positively associated with offspring airway obstruction ( FEV1/ FVC < 75%). Compared to offspring in the first tertile of exposure, offspring in the third tertile of dioxin-like PCB exposure had an OR of 2.96 (95% CI: 1.14-7.70). Similar associations for non-dioxin-like PCBs, HCB, and p,p'- DDE were 2.68 (1.06-6.81), 2.63 (1.07, 6.46), and 2.87 (1.09, 7.57), respectively. No associations were observed with reduced lung function ( FEV1% of predicted value < 90%). Conclusion and Clinical Relevance Our data indicate that prenatal exposure to POPs appears to be associated with airway obstruction but not allergic sensitization at 20 years of age. The findings support that chronic obstructive lung diseases may have at least part of their origins in early life. [ABSTRACT FROM AUTHOR]

Background Airway hyperresponsiveness (AHR) to inhaled mannitol is associated with indirect markers of mast cell activation and eosinophilic airway inflammation. It is unknown how AHR to mannitol relates to mast cell phenotype, mast cell function and measures of eosinophilic inflammation in airway tissue. We compared the number and phenotype of mast cells, mRNA expression of mast cell-associated genes and number of eosinophils in airway tissue of subjects with asthma and healthy controls in relation to AHR to mannitol. Methods Airway hyperresponsiveness to inhaled mannitol was measured in 23 non-smoking, corticosteroid-free asthmatic individuals and 10 healthy controls. Mast cells and eosinophils were identified in mucosal biopsies from all participants. Mast cells were divided into phenotypes based on the presence of chymase. mRNA expression of mast cell-associated genes was measured by real-time PCR. Results The proportion of submucosal MCTC was higher in asthmatic individuals with AHR to mannitol compared with asthmatic individuals without AHR (median: 40.3% vs. 18.7%, P = 0.03). Increased submucosal MCTC numbers were associated with increased levels of mRNA for thymic stromal lymphopoietin (TSLP) and CPA3 in asthmatics. Reactivity to mannitol correlated significantly with eosinophils in submucosa ( r(s): 0.56, P = 0.01). Conclusion Airway hyperresponsiveness to inhaled mannitol is associated with an altered submucosal mast cell profile in asthmatic individuals. This mast cell profile is associated with increased levels of TSLP and CPA3. The degree of AHR to mannitol is correlated with the degree of eosinophilic inflammation in the airway submucosa. [ABSTRACT FROM AUTHOR]

The interrelation of thermodynamics and statistical properties of quantum systems can be demonstrated with comparatively little mathematical effort using two state systems (or two state particles). Basic results are summarized for this model system. The entropy can be interpreted as the entropy of mixing particles in their low and high energy state. Thus, an apparent single component system can be considered as a two component system with variable particle numbers. This result has recently been generalized for elementary bosonic and fermionic systems or particles with many different excited states. In this case, one has to take into account as many components as different internal states of the particles are available. The numbers of particles of each component, however, are not constant but depend on the temperature at thermal equilibrium according to statistical principles. In the literature, the concept of negative internal temperatures was previously introduced to characterize and describe special inverted occupation probabilities out of thermal equilibrium. This interpretation of inverted occupation numbers is revisited explicitly for nuclear spin systems. The interpretation of inverted occupancy by negative temperature is based on ignoring athermal contributions to the internal energy due to the inversion procedure. Accordingly, negative temperatures are not justified in the case of systems out of thermal equilibrium but seem to be misleading and confusing. Instead, the different states of the particles represent distinctive components possessing different chemical potentials, magnetic moments or other properties. The present paper intends to remove the confusion about negative temperatures. It shows how processes out of thermal equilibrium are described and understood without difficulties by balancing the different kinds of particles together with their energy and production of entropy within the framework of thermodynamics. [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]

Entropy as a function of temperature at constant volume, S(T), can be determined by integrating the molar specific entropy capacity CV/T (CV: molar specific heat capacity at constant volume). As a second approach, S(T) at constant volume can be determined by differentiating the free energy with respect to the temperature, T. Recently, it has been shown for a system obeying Boltzmann statistics that these mathematical approaches are equivalent to applying the formula of the mixing entropy, if the ground and excited states of the same sub-systems or elementary systems are considered as mixing objects or quantum components. This result considerably extends the applicability of the formula of the mixing entropy, which is derived in textbooks just for mixing real indifferent components. In the present paper, it is shown that the formula of the mixing entropy can also be applied to calculate the entropy of Bose and Fermi systems. Thus, all entropy can be calculated and interpreted as mixing entropy of real components or quantum components. In reverse, the transitions between the ground and the excited states of any system can be explained as mixing processes. This interpretation is applied to the melting transition of chemically bonded solids and in particular to the glass transition whereby upon cooling the mixing entropy of the melt is (at least partly) frozen in the configuration. These results suggest a new interpretation of the glass transition and a new definition of structural glass. [ABSTRACT FROM AUTHOR]

Background The toll-like receptors, TLR5 and TLR7, have recently been proposed in asthma immunopathogenesis. While supporting data come from animal or in vitro studies, little is known about TLR5 and TLR7 expression in human asthmatic airways. Methods Advanced immunohistochemical mapping of TLR5 and TLR7 was performed on bronchial and transbronchial biopsies from healthy individuals and patients with moderate and severe asthma. Results TLR5 was identified in multiple structural cells; bronchial epithelium, alveolar type II pneumocytes, plasma cells, macrophages and neutrophils. Contrary to bronchial TLR5, which had a basolateral expression, alveolar TLR5 had polarized apical localization. Patients with severe asthma had decreased total and epithelial TLR5 expression compared to controls and moderate asthmatics ( P < 0.001). TLR7 expression was found in several structural cells and asthma-related immune cells. Whereas TLR7 expression was decreased in severe asthmatics ( P < 0.001), nerve-associated TLR7 increased ( P = 0.035). Within the asthma groups, both TLR5 and TLR7 expression correlated with multiple lung function parameters. Conclusions Our results reveal broad expression patterns of TLR5 and TLR7 in the lung and that the expression is decreased in severe asthma. Hence, severe asthmatics may suffer from insufficient TLR signalling during viral or bacterial infections leading to poor and impaired defence mechanisms. [ABSTRACT FROM AUTHOR]

The function of cultured mast cells may depend on genetic or environmental influence on the stem cell donor. This study investigates whether asthma or atopy in the donor influenced the growth and sensitivity of mast cells cultured from patients with asthma and healthy controls under identical conditions. Mast cells were cultured from peripheral blood from twelve patients with an objectively confirmed asthma diagnosis and eight healthy subjects. During the last 2 weeks of culture, mast cells were incubated with IL-4 and 80 kU/l recombinant human Ig E containing two clones (7% + 7%) specific for mite allergen Der p2. The sensitivity of Ig E-mediated activation of mast cells was investigated as Fcε RI-mediated upregulation of CD63. Ten subjects were atopic, defined as a positive skin prick test (>3 mm) to at least one of ten common allergens. After activation with recombinant Der p2, the maximum CD63 median fluorescence intensity was 20 456 ± 1640 ( SE) for patients with asthma and 22 275 ± 1971 ( SE) for controls (ns). The fraction of CD63 positive cells was 54.4% in patients with asthma and 48.4% in controls (ns). The allergen concentration inducing 50% of the maximal CD63 response was similar in patients with asthma [−0.4795 log ng/ml ± 0.092 ( SE)] and controls (−0.6351 log ng/ml ± 0.083, ns) and in atopic and non-atopic subjects. When cultured, sensitized and activated under identical conditions, mast cells from allergic asthmatics and healthy controls respond similar. Activation of cultured mast cells appears to depend on culture conditions ( IL-4, Ig E) rather than on donor status as atopy and asthma. [ABSTRACT FROM AUTHOR]

The Legendre transformation has found widespread application in thermodynamics, Hamilton-Lagrange-mechanics and optics. It attributes the values of the coordinates ( x, y ( x)) representing the points of a monotonic piecewise smooth functional curve y ( x) the slopes mx ( x) = dy ( x)/ dx and the intercepts y ( mx) of their tangents on the y-axis. Thus, the initial curve y ( x) is represented by the ordered set of all slopes mx ( x) = dy ( x)/ dx of its tangents together with their intercepts y ( mx) on the y-axis. It is shown that the transformed or conjugated function must basically be supplemented by a homogeneous linear function of the relevant variable. This is usually neglected in the literature. In addition, a new interpretation of the Legendre transformation is presented and discussed: For this purpose the derivative mx ( x) is considered as the proper initial function and integrated between x0 and x. This integral is complemented by the integral of x ( mx) ((the inverse function of mx ( x)) over mx between mx0 = mx ( x0) and mx ( x), if mx ( x) and x ( mx) are strictly monotonic. The sum of both integrals yields the 'area' ( xmx - x0 mx0). Legendre's transformation is obtained by reordering the respective terms. The procedure of transformation corresponds to integration by parts. Some examples and consequences of the properties considered are demonstrated and discussed using the simple model of two-state systems. The general results of the present work remove possible internal inconsistencies in thermodynamics. [ABSTRACT FROM AUTHOR]

In order to understand the thermodynamic properties of solids and melts one has to consider simultaneously their entropy and energy as a function of temperature. Therefore, the molar entropy, S, and enthalpy (energy), H, of crystals, glasses and melts of the same one-component systems have been suitably depicted including the transformation from the melt into a solid, i. e. a glass or crystal. S and H of glasses correspond to a simple continuation of these functions from the molten state to lower temperatures. Since crystallisation occurs spontaneously such a process necessarily produces entropy causing the temperature to increase. Thus, the glassy and the crystalline state are not connected by an isothermal process, which is in contrast to the assumption in the classical nucleation and crystallisation theory as well as in the arguments causing Kauzmann's paradox. For the temperature T → 0 K the enthalpy and entropy of the glass are larger by Δ H0 and Δ S0 as compared to the stable crystal. The calculations are illustrated using experimental data for quartz and silica glass from P. Richet, Y. Bottinga, L. Deniélou, J. P. Petitet and C. Téqui. [ABSTRACT FROM AUTHOR]

Mast cells have long been recognized as the principal cell type that initiates the inflammatory response characteristic of acute allergic type 1 reactions. Our goal has been to further characterize maturation of progenitors to mast cells.Mast cells were cultured from human cord blood derived CD133+ progenitors. Mast cell function was tested using histamine release. During differentiation mast cells surface marker expression was monitored by flow cytometry.CD133+ progenitors expressed the early haematopoietic and myeloid lineage markers CD34, CD117, CD13 and CD33. Mature mast cells expressed CD117, CD13 and CD33, and expression of the high affinity immunoglobulin E recpetor FcℇRI increased during culture. Cytokine receptors interleukin (IL)-5R, IL-3R,granulocyte-macrophage-colony stimulating factor (GM-CSF)R and IL-18R were expressed at high levels during maturation. Chemokine receptors CXCR4 and CXCR2 were highly expressed on both newly purified CD133+ cells and mature cells.Human mast cells can be cultured from a CD34+/CD117+/CD13+/CD33+ progenitor cell population in cord blood that is tryptase and chymase negative. Developing and mature mast cells express a wide range of chemokine and cytokine receptors. We found high levels of expression of CD123, IL-5R and GM-CSF receptors, also found on eosinophils and basophils, and high levels of expression of the receptor for the inflammatory cytokine IL-18. [ABSTRACT FROM AUTHOR]

Summary Background Atopy is closely associated with the cellular T helper type-2 (Th2) phenotype, that is dominated by the pleiotrophic cytokine IL-4. The cellular source of IL-4 has yet to be determined, although basophils have been proposed. Eosinophils and mast cells are likely contenders investigated here, and the eosinophil-like leukaemia line AML14.3D10 is compared to eosinophils as an in vitro culturable model for eosinophils. Lectins can cross-link-specific surface glycoproteins and are found in the ingested (processed foods) and inhaled (airborne pollen grains) human environment. Therefore it is of interest to determine whether lectins can elicit the release of IL-4 from Th2-associated granulocytes other than basophils. Method This study investigated the ability of eosinophils, AML14.3D10 and mast cells to secrete preformed IL-4 in response to stimulation with lectins, and explored molecular mechanisms underlying the interaction. Results Purified eosinophils and basophils, and cultured mast cells and AML14.3D10 cells were incubated with 1 µm lectin. Agglutination was scored by microscopy. IL-4 secretion was measured by enayme-linked immunosorbent assay. Biotinylated lectins were used to determine binding to cells by flow cytometry and in lectin blots of sodium dodecyl sulphate (SDS) gels. Discussion Purified human eosinophils, AML14.3D10 cells and cultured mast cells secrete IL-4 with a pattern similar to that found in basophils when stimulated with a panel of reactive and unreactive lectins. The lectin SNA induces IL-4 secretion from mast cells and basophils, but not from eosinophils or AML14.3D10. Eosinophils appear to secrete only pre-formed IL-4, whereas mast cells may synthesize IL-4 on ligation with the lectin LCA. Lectins that agglutinate the granulocytes investigated do not necessarily induce secretion of IL-4. Lectins that elicit secretion of IL-4 bind more to eosinophils than unreactive lectins as determined by flow cytometry and lectin... [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The basophil activation test (BAT) has become a pervasive test for allergic response through the development of flow cytometry, discovery of activation markers such as CD63 and unique markers identifying basophil granulocytes. Basophil activation test measures basophil response to allergen cross-linking IgE on between 150 and 2000 basophil granulocytes in <0.1 ml fresh blood. Dichotomous activation is assessed as the fraction of reacting basophils. In addition to clinical history, skin prick test, and specific IgE determination, BAT can be a part of the diagnostic evaluation of patients with food-, insect venom-, and drug allergy and chronic urticaria. It may be helpful in determining the clinically relevant allergen. Basophil sensitivity may be used to monitor patients on allergen immunotherapy, anti-IgE treatment or in the natural resolution of allergy. Basophil activation test may use fewer resources and be more reproducible than challenge testing. As it is less stressful for the patient and avoids severe allergic reactions, BAT ought to precede challenge testing. An important next step is to standardize BAT and make it available in diagnostic laboratories. The nature of basophil activation as an ex vivo challenge makes it a multifaceted and promising tool for the allergist. In this EAACI task force position paper, we provide an overview of the practical and technical details as well as the clinical utility of BAT in diagnosis and management of allergic diseases., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)