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Allergic hypersensitivity of type I for hymenoptera venoms is the most frequent reason for acute IgE-mediated anaphylactic reactions. The subcutaneous injection of increasing doses of purified allergen followed by long-term administration of an adequate maintenance dose over a period of 3-5 years called venom immunotherapy (VIT) has been proven to be a very effective treatment achieving protection in about 96% of allergic patients. Even though the principle of hyposensitisation has been introduced already 90 years ago, the underlying immunoregulatory mechanisms of VIT remain poorly understood. Recent studies suggest a shift in cytokine production from a Th2 to a Th1 cytokine profile during therapy. In this paper, a mathematical model for T-cell regulation and a model for mast cell/basophil desensitisation are presented and analysed to explain the mechanism of conventional rush and ultra-rush VIT. [ABSTRACT FROM AUTHOR]

Aspirin desensitization (AD) is an effective treatment in patients with non-steroidal anti-inflammatory drugs (NSAID)-exacerbated respiratory disease (NERD) by providing inhibitory effect on symptoms and polyp recurrence. However, limited data is available on how AD works. We aimed to study comprehensively the mechanisms underlying AD by examining basophil activation (CD203c upregulation), mediator-releases of tryptase, CysLT, and LXA4, and LTB4 receptor expression for the first 3 months of AD. The study was conducted in patients with NERD who underwent AD (group 1: n = 23), patients with NERD who received no desensitization (group 2: n = 22), and healthy volunteers (group 3, n = 13). All participants provided blood samples for flow cytometry studies (CD203c and LTB4 receptor), and mediator releases (CysLT, LXA4, and tryptase) for the relevant time points determined. All baseline parameters of CD203c and LTB4 receptor expressions, tryptase, CysLT, and LXA4 releases were similar in each group (p > 0.05). In group 1, CD203c started to be upregulated at the time of reactions during AD, and continued to be high for 3 months when compared to controls. All other study parameters were comparable with baseline and at the other time points in each group (p > 0.05). Although basophils are active during the first 3 months of AD, no releases of CysLT, tryptase or LXA4 exist. Therefore, our results suggest that despite active basophils, inhibition of mediators can at least partly explain underlying the mechanism in the first three months of AD. [ABSTRACT FROM AUTHOR]

Background and aim: Alpha-momorcharin (α-MMC) is a type I ribosome-inactivating protein (RIP) that is purified from Momordica charantia. Despite its strong antitumor activities, α-MMC exerts the undesirable immunotoxicity effects of hypersensitivity or immunosuppression. Since α-MMC is a plant protein, its application in vivo can easily induce hypersensitivity, but its immunosuppressive mechanism is still unclear. Materials and methods: The toxicity of α-MMC to peripheral blood cells and the cytokine expression in peripheral blood mononuclear cells (PBMCs) and spleen immune cells were measured in rats. For further confirmation, experiments were performed in vitro with the mononuclear cell line THP-1, B lymphocyte cell line WIL2-S and T lymphocyte cell line Jurkat. Results: High doses of α-MMC (3.0 mg/kg) resulted in weight loss in rats, a decreased percentage of monocytes, and increased percentages of eosinophils and basophils. Both high-dose and low-dose (1.0 mg/kg) α-MMC inhibited cytokine expression in PBMCs and increased cytokine expression in spleen T cells. In in vitro, α-MMC mainly acted on THP-1 cells, with effects including high dose-induced apoptosis and low dose-induced regulation of inhibitory cytokine expression. Conclusions: The action of α-MMC on immune cells mainly affects monocytes, thereby eliciting its immunosuppressive effect. Its mode of action is to guide functional immunosuppressive regulation at low doses and induce apoptosis at high doses. As the monocytes would be recruited into tumor tissues and are polarized into tumor-associated macrophages, the selective cytotoxicity and cytokine release regulation of α-MMC in monocytes may be an important mechanism of its antitumor effects. [ABSTRACT FROM AUTHOR]

Background: Drug hypersensitivity reactions of immediate type pose a challenging problem, especially, if standard diagnostic procedures do not lead to conclusive results. The aim of this investigation is to identify, whether basophil activation test (BAT) is able to provide additional benefit in the diagnostic evaluation of immediate type drug hypersensitivity reactions to antibiotics in comparison with the routine allergological diagnostic methods. Materials and methods: We investigated patients, who presented to the Department of Dermatology and Allergology of the University Hospital of RWTH Aachen in Germany for diagnostic workup of type I allergic reactions to antibiotics during the period from 2009 to 2012. The analysis was performed retrospectively based on patient records. The inclusion criteria were performed standard allergological in vivo diagnostic and a BAT as a part of diagnostic workup. Results: Eighty-two diagnostic investigations were performed in 52 patients. BAT was positive in 9 of 12 cases with a positive clinical history but negative skin test results. Furthermore, all patients who reported severe drug hypersensitivity reactions (anaphylactic reaction grade 2 and above) showed positive BAT (5/5), while only three of these five cases demonstrated a positive skin testing that led to the conclusion of possible immediate type drug hypersensitivity. Conclusions: Although skin tests remain the most important part of the primary diagnostic investigation, BAT is an additional valuable and sensitive in vitro test in the diagnostic procedure of immediate type allergic reactions to antibiotics. However, further standardized investigations are needed in order to calculate exact sensitivity and specificity of this diagnostic tool in both, adult and pediatric populations. [ABSTRACT FROM AUTHOR]

Introduction: Betalactams are the most widely used drugs against infections and the primary cause of antibiotic hypersensitivity reactions. Reaction patterns for different betalactams have been changing in accordance with consumption trends, and vary among countries. As a consequence,in vivoandin vitrotests have had to change with to keep up with new tendencies. Areas covered: This review is focused on advances in betalactam hypersensitivity diagnosis. Changes inin vivomethods have been limited to the inclusion of new haptens. In contrast, major progress has been achieved forin vitrotests since the 1960s, from the first description of immunoassays, the basophil activation test and the lymphocyte transformation test, to the more sophisticated assays developed in last years. Expert commentary: Issues with diagnosis are related to test sensitivity.In vivotests show higher sensitivity, however they can be risky, especially in severe and life-threatening reactions. Therefore, we believe thatin vitrotests should be the preferred method. Current efforts are under way to enhance their sensitivity. Only multidisciplinary approaches involving immunology, proteomics, nanotechnology and chemistry can help us to fully understand conjugate structures and mechanisms involved in hypersensitivity reactions to betalactams, and consequently lead to advances inin vitromethods. [ABSTRACT FROM PUBLISHER]

Food allergy is an important public health problem that affects an estimated 8% of young children and 2% of adults. With an increasing interest in genetically-engineered foods, there is a growing need for development of sensitive and specific tests to evaluate potential allergenicity of foods and novel proteins as well as to determine allergic responses to ensure consumer safety. This review covers progress made in the field of development of cell models, specifically that involving a rat basophil leukemia (RBL) cell-based immunoassay, for use in allergen identification, diagnosis, and immunotherapy. The RBL assay has been extensively employed for determining biologically relevant cross-reactivities of food proteins, assessing the effect of processing on the allergenicity of food proteins, diagnosing allergic responses to whole-food products, and identifying anti-allergy food compounds. From the review of the literature, one might conclude the RBL cell-based assay is a better test system when compared to wild-type mast cell and basophil model systems for use in allergen identification, diagnosis, and analyses of potential immunotherapeutics. However, it is important to emphasize that this assay will only be able to identify those allergens to which the human has already been exposed, but will not identify a truly novel allergen, i.e. one that has never been encountered as in its preferred (humanized) configuration. [ABSTRACT FROM AUTHOR]

Acute basophilic leukemia is a distinct entity of Acute Myeloid Leukemia (AML) with primary differentiation to basophils. Increased basophil count has been described in AML cases with translocation t(6;9)(p23;q34) or other chromosomal abnormalities. We describe a 15-year old female teenager with AML and excess peripheral blood and bone marrow basophils. Her white blood cell count at diagnosis was 15.4 G/L with 53% basophils and 17% blasts. The bone marrow cytogenetics analysis did not reveal any of the usual abnormalities. The karyotype showed two closely related leukemic clones: the first (16 metaphases), with a total of 48 chromosomes, had an extra chromosome 8 with deletion of the long arm and an additional 21 (48,XX, +del(8)(q24.2q24.3), t21[16]), while the second clone (2 metaphases), with a total of 47 chromosomes, did not contain the extra 21 chromosome (47, sl, −21[2]). In summary, in this case of AML-M2 with excess basophils, there is a novel chromosomal abnormality, not previously reported in this entity. [ABSTRACT FROM AUTHOR]

Hematological and biochemical profiles commonly are required in equine medicine. We studied hematological parameters including red blood cells (RBC), white blood cells (WBC), hemoglobin (Hb), hematocrit (PCV), differential leukocyte counts, mean cell volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) in thoroughbred foals at different ages and for both sexes. Sixty healthy thoroughbred foals, 1 day, 3 days and 1 year old were used. Each age group consisted of 10 male and 10 female animals. We found significant differences related to age in RBC values of females, PCV, MCV values of males, WBC, neutrophil percentages, lymphocyte percentages, monocyte percentages of females, and eosinophil percentages and basophil percentages. Significant differences related to gender were found only with regard to PCV at 1 year and WBC at 1 day. The hematological parameters of thoroughbred foals up to one year old may be useful for evaluating and monitoring the health of these animals. [ABSTRACT FROM AUTHOR]

Recurrent herpes stromal keratitis (HSK) is one of the leading causes of blindness in the developed world. Cyokines characteristic of Th1 cells (in particular IFN-γ and IL-2) have been shown to dominate in HSK in addition to mechanisms by nonspecific, antigen-independent effector cells such as neutrophils, basophils, and monocytes. More recently, the migration and maturation of dendritic cells (DC) within the corneal stroma of patients with HSK have been recognized as contributors to recurrent disease, suggesting a role for delayed type hypersensitivity (DTH) in the immunopathogenesis of HSK. The role of DC and DTH in recurrent HSK has not been studied extensively and experimental models of recurrent HSK focusing on DTH as the pathogenesis and viral particles as the triggering antigen may contribute to better understanding of the disease. [ABSTRACT FROM AUTHOR]

Background. Toll-like receptor (TLR) molecules play critical roles in directing the course of atopic diseases by recognizing specific microbial products that activate immune effector cell function. Objective. We determined if basophils harvested from neonates genetically predisposed to atopic disease had different levels of TLR2 expression and determined whether putative TLR2 ligands mediated cytokine secretion. Methods. Blood samples were collected from 10 asthmatic and 12 healthy women and their newborns. Basophil histamine was measured using the human basophil degranulation test and TLR2 expression was determined using nucleic acid hybridization in situ and flow cytometry. IL-4 levels were quantified by ELISA following allergen stimulation. Results. The basophil degranulation index (DI) in granulocytes harvested from peripheral blood of asthmatic women was assessed following stimulation with either peptidoglycan (PGN) or Dermatophagoides farinae (Df) extract. The DI was significantly higher in atopic women than in healthy controls. Basophils purified from the cord blood of neonates born to atopic mothers produced more IL-4 compared with basophils purified from children born to nonatopic controls. Finally, TLR2 expression at the protein and mRNA levels was upregulated in cord blood basophils from neonates born to mothers with asthma following stimulation with PGN but not Df. Conclusion. These data suggested that TLR2-mediated innate immune responses play a role in augmenting allergic reactions through the modulation of basophil cytokine secretion and histamine release. Microbial components may activate basophils through TLR2 (especially for genetically predisposed infants) to release cytokines associated with an increased incidence of allergic diseases. [ABSTRACT FROM AUTHOR]

Hypersensitivity reactions to drugs account for 15% of all adverse drug reactions and represent an important health problem with significant morbidity and mortality. This article describes the current applications and perspectives of the basophil activation test by flow cytometry in the diagnosis of immediate-type drug allergy, with particular focus on its diagnostic performance in allergy to neuromuscular blocking agents, antibiotics and NSAIDs and on future applications. INSET: Key issues. [ABSTRACT FROM AUTHOR]

A patient entered hospital with a puzzling absolute monocytosis. Admitting blood smears had been stained with Diff-Quik, a Romanowsky stain. When additional smears were stained using a standard Malachowski-Wright-Giemsa method, the reason for the monocytosis became abundantly clear. [ABSTRACT FROM AUTHOR]

We conducted enzyme-linked immunosorbent assay (ELISA) and basophil-activation assay in order to investigate the presence of allergens in selected cow milk (CM) substitutes. Our results showed the presence of residual antigenicity and allergenicity. The cross-reactivity between proteins from different animal species was observed. CM allergen-induced histamine release was dose-dependent. Therefore, differences in the relative percentage of major allergens may lead to a discrepancy between allergenic and antigenic activity. The presence of very similar epitopes could explain the cross-reactivity in mammalian milks. [ABSTRACT FROM AUTHOR]

Objective. Functional dyspepsia is a common gastrointestinal disorder. The pathogenesis of functional dyspepsia remains unclear. Functional dyspepsia may begin after a bout of gastroenteritis (post-infectious functional dyspepsia) or de novo (nonspecific functional dyspepsia). The aim of this study was to investigate the prevalence and probable mechanisms of post-infectious functional dyspepsia. Material and methods. Functional dyspepsia patients with a history of unsanitary food intake and acute gastroenteritis 6-12 months ago were enrolled. 13C-UBT confirmed absence of H. pylori infection. Controls consisted of healthy nondyspeptic volunteers and patients with nonspecific functional dyspepsia. Gastric biopsies were used for routine histology, immunohistochemistry, electron microscopy, ELISA, HPLC assays and Western blot examination. Results. Eighty-five subjects were entered including 35 with post-infectious functional dyspepsia, 30 with nonspecific functional dyspepsia, and 20 healthy controls. The number of mast cells in post-infectious functional dyspepsia and nonspecific functional dyspepsia were significantly greater than that in healthy controls. The number of enterochromaffin cells (ECs) in post-infectious functional dyspepsia was significantly higher than those in nonspecific functional dyspepsia or in healthy controls. The number of mast cells and ECs increased with the density of chronic inflammatory cells. The release of histamine and 5-hydroxytryptamine from gastric mucosa of post-infectious functional dyspepsia patients was significantly greater than those from nonspecific functional dyspepsia or healthy controls. Tryptase protein expression was higher in post-infectious functional dyspepsia and nonspecific functional dyspepsia than in healthy controls. The histological score of chronic gastric inflammation was greater in post-infectious functional dyspepsia versus patients with nonspecific functional dyspepsia or healthy controls. Electron microscopy showed secreting granules in the cytoplasm of both mast cells and ECs. The number of activated mast cells and Ecs at a distance of < 5 μm of nerve fibers were significantly greater in post-infectious functional dyspepsia versus nonspecific functional dyspepsia or controls. Conclusions. Dyspepsia may occur after an acute onset of gastroenteritis in a part of patients. Potent chemicals derived from mast cells and ECs, including histamine, tryptase and 5-hydroxytryptamine may be involved in the pathogenesis of post-infectious functional dyspepsia. [ABSTRACT FROM AUTHOR]

Basophils are relatively rare leukocytes that potentially play a role in both systemic anaphylaxis and, owing to their ability to migrate from the blood into various other tissues, in more localized aspects of allergic inflammation. Given their greater sensitivities to allergen provocation compared with their tissue-fixed mast cell counterparts, and by virtue of their capacity to more readily generate Th2-type cytokines, basophils have been considered to play more than a bystander role in initiating and maintaining allergic disorders. However, only very recently has clearer evidence shed light on the abilities of this cell type to orchestrate chronic allergic inflammation and promote Th2 immunity in the early induction stages of allergy. This review summarizes these recent advances in understanding the role of basophils in orchestrating and maintaining allergic responses. INSET: Key issues. [ABSTRACT FROM AUTHOR]

The question whether pesticides can modulate allergy relevant reactions is a controversial issue. In the allergist's office many food-allergic patients believe themselves to react particularly to 'chemically treated' food, especially fruits. Investigations on the influence of pesticides upon apple allergy should bring the problem closer to scientific understanding. Apples of the variety 'Golden Delicious' from 'biologic-dynamic' cultivation and the pesticides chlorpropham and thiram were studied in the experiments. Self-prepared apple protein extracts as well as the pesticides were examined in the in vitro mediator release test from human basophil granulocytes either alone or in combination (spiking experiments). The mediators histamine and leukotriene C[sub 4] were measured by high-performance liquid chromatography (HPLC). The possible binding of chlorpropham to the apple protein was examined using the enzyme allergosorbent test and immunoblotting with chlorpropham spiked apple allergen extracts. Chlorpropham but not thiram acted as a direct histamine liberator. Leukotriene C[sub 4] secretion was not induced by any pesticide. In the spiking experiments, when chlorpropham was added to apple extract, it showed a concentration dependent inhibition of histamine release compared to thiram, which had no effect. In an HPLC examination a binding of chlorpropham to apple protein up to 13% could be observed. In the enzyme allergosorbent test chlorpropham caused a reduced specific IgE antibody binding to the apple protein. In the immunoblot there was weakening by chlorpropham of the 18 kDa major allergen band (Mal d I). It is assumed that chlorpropham modulates the apple allergens leading to reduced antibody binding thereby decreasing allergenic potency. [ABSTRACT FROM AUTHOR]