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Derived from the myeloid lineage, granulocytes, including basophils, eosinophils, and neutrophils, along with mast cells, play important, often disparate, roles across the allergic disease spectrum. While these cells and their mediators are commonly associated with allergic inflammation, they also exhibit several functions either promoting or restricting tumor growth. In this Position Paper we discuss common granulocyte and mast cell features relating to immunomodulatory functions in allergy and in cancer. We highlight key mechanisms which may inform cancer treatment and propose pertinent areas for future research. We suggest areas where understanding the communication between granulocytes, mast cells, and the tumor microenvironment, will be crucial for identifying immune mechanisms that may be harnessed to counteract tumor development. For example, a comprehensive understanding of allergic and immune factors driving distinct neutrophil states and those mechanisms that link mast cells with immunotherapy resistance, might enable targeted manipulation of specific subpopulations, leading to precision immunotherapy in cancer. We recommend specific areas of investigation in AllergoOncology and knowledge exchange across disease contexts to uncover pertinent reciprocal functions in allergy and cancer and allow therapeutic manipulation of these powerful cell populations. These will help address the unmet needs in stratifying and managing patients with allergic diseases and cancer. [ABSTRACT FROM AUTHOR]

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]

An autoimmune subset of chronic spontaneous urticaria is increasingly being recognized internationally, based on laboratory and clinical evidence that has accrued over the last 20 years. This evidence has been reviewed by a taskforce of the Dermatology section of the European Academy of Allergy and Clinical Immunology. Functional autoantibodies in chronic urticaria ( CU) patient sera have been demonstrated against Ig E and Fcε RIα by basophil and mast cell histamine release assays and by basophil activation assays. Antibody specificity has been confirmed by immunoassay, but there is a poor correlation between functionality and immunoreactivity. Approximately 25% of CU patients have a positive basophil histamine release assay and show autoreactivity (a positive autologous serum skin test), whereas 50% are negative regarding both. Functionality of CU sera appears to be complement dependent on mast cells but not exclusively on basophils. Basophil activation by CU sera is predominantly restricted to Ig G1 and Ig G3 subclasses. Circumstantial evidence for CU being an autoimmune disease comes from an observed association with other autoimmune diseases, a strong association between serum functionality and HLA- DR4 haplotype and the good response of CU patients to immunotherapies. It was proposed that a study should be undertaken to prospectively validate potentially relevant clinical criteria (from the history, examination and routinely available clinical investigations) against a new 'gold standard' for the diagnosis of ACU (positive autoreactivity, functional bioassay and immunoassay) to define preliminary criteria sets for the diagnosis of ACU based on clinical and laboratory features with highest individual sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Leukocytes are mainly composed of neutrophils, basophils, eosinophils, monocytes, and lymphocytes. The number and proportion of different types of leukocytes correspond to different diseases, so an accurate segmentation of each type of leukocyte is important for the diagnosis of disease. However, the acquisition of blood cell images can be affected by external environmental factors, which can lead to variable light and darkness, complex backgrounds, and poorly characterized leukocytes. To address the problem of complex blood cell images collected under different environments and the lack of obvious leukocyte features, a leukocyte segmentation method based on improved U-net is proposed. First, adaptive histogram equalization-retinex correction was introduced for data enhancement to make the leukocyte features in the blood cell images clearer. Then, to address the problem of similarity between different types of leukocytes, convolutional block attention module is added to the four skip connections of U-net to focus the features from spatial and channel aspects, so that the network can quickly locate the high-value information of features in different channels and spaces. It avoids the problem of large amount of repeated computation of low-value information, prevents overfitting, and improves the training efficiency and generalization ability of the network. Finally, to solve the problem of class imbalance in blood cell images and to better segment the cytoplasm of leukocytes, a loss function combining focal loss and Dice loss is proposed. We use the BCISC public dataset to verify the effectiveness of the proposed method. The segmentation of multiple leukocytes using the method of this paper can achieve 99.53% accuracy and 91.89% mIoU. The experimental results show that the method achieves good segmentation results for lymphocytes, basophils, neutrophils, eosinophils, and monocytes. [ABSTRACT FROM AUTHOR]

In the absence of their natural hosts animal fleas can bite man. Various stages of sensitization seem to occur and the sufferers may show immediate urticarical or delayed popular skin reactions. Mast cells contain high concentrations of various inflammation mediators especially for allergic reactions including histamine and protinases. Human mast cells have shown to differ markedly from mast cells in several animal species.

Helminths are multicellular parasites that are a substantial problem for both human and veterinary medicine. According to estimates, 1.5 billion people suffer from their infection, resulting in decreased life quality and burdens for healthcare systems. On the other hand, these infections may alleviate autoimmune diseases and allergy symptoms. The immune system is programmed to combat infections; nevertheless, its effector mechanisms may result in immunopathologies and exacerbate clinical symptoms. This review summarizes the role of the immune response against worms, with an emphasis on the Th2 response, which is a hallmark of helminth infections. We characterize non-immune cells (enteric tuft cells—ETCs) responsible for detecting parasites, as well as the role of hematopoietic-derived cells (macrophages, basophils, eosinophils, neutrophils, innate lymphoid cells group 2—ILC2s, mast cells, T cells, and B cells) in initiating and sustaining the immune response, as well as the functions they play in granulomas. The aim of this paper is to review the existing knowledge regarding the immune response against helminths, to attempt to decipher the interactions between cells engaged in the response, and to indicate the gaps in the current knowledge. [ABSTRACT FROM AUTHOR]

White blood cells (WBCs) in the human immune system defend against infection and protect the body from external hazardous objects. They are comprised of neutrophils, eosinophils, basophils, monocytes, and lymphocytes, whereby each accounts for a distinct percentage and performs specific functions. Traditionally, the clinical laboratory procedure for quantifying the specific types of white blood cells is an integral part of a complete blood count (CBC) test, which aids in monitoring the health of people. With the advancements in deep learning, blood film images can be classified in less time and with high accuracy using various algorithms. This paper exploits a number of state-of-the-art deep learning models and their variations based on CNN architecture. A comparative study on model performance based on accuracy, F1-score, recall, precision, number of parameters, and time was conducted, and DenseNet161 was found to demonstrate a superior performance among its counterparts. In addition, advanced optimization techniques such as normalization, mixed-up augmentation, and label smoothing were also employed on DenseNet to further refine its performance. [ABSTRACT FROM AUTHOR]

Anaphylaxis is a life-threatening or even fatal systemic hypersensitivity reaction. The incidence of anaphylaxis has risen at an alarming rate in the past decades in the majority of countries. Generally, the most common causes of severe or fatal anaphylaxis are medication, foods and Hymenoptera venoms. Anaphylactic reactions are characterized by the activation of mast cells and basophils and the release of mediators. These cells express a variety of receptors that enable them to respond to a wide range of stimulants. Most studies of anaphylaxis focus on IgE-dependent reactions. The mast cell has long been regarded as the main effector cell involved in IgE-mediated anaphylaxis. This paper reviews IgE-independent anaphylaxis, with special emphasis on mast cells, basophils, anaphylactic mediators, risk factors, triggers, and management. [ABSTRACT FROM AUTHOR]

White blood cells (Leukocytes) are considered to be an essential part of the human body's immune system. The count of WBCs is considered to be a parameter for the indication of disease. Over time several methods have been proposed to classify these WBCs into their subtypes namely Neutrophils, Eosinophils, Basophils, Lymphocytes, and Monocytes which helps in the estimation of the body's WBC count. These methods range from various morphological image processing-based methodologies to advanced deep neural systems. Due to the superior ability of neural systems to achieve the state of the art results more research is been carried out in this field. However, most of the such previously proposed methods have concentrated only in establishing and explaining the overall methodology for achieving high accuracy scores and less emphasis has been made in discussing the impact of modular changes in such methodologies like the impact of various activation functions, optimizers and data pre-processing methods very explicitly for this problem. This has led to a deficiency of work to be carried out with very recently developed activation functions and more essentially optimization algorithms other than backpropagation. It is extremely essential to explore and analyse different modules of the methodology to accelerate future research work further which might possibly help the research community in achieving a much better and efficient solution. This paper compares various architectures and discusses the behaviour and impact of different hyperparameters and proposes a novel methodology by incorporating recently developed swish activation to enhance the results. Unlike previously proposed methods of proposing single better neural network model this paper suggests a good choice of modular changes that could be incorporated in future works to enhance their results. [ABSTRACT FROM AUTHOR]

This paper presents a novel medical image processing technique for analyzing different peripheral blood cells such as monocytes, lymphocytes, neutrophils, eosinophils, basophils, and macrophages. However, the existing systems suffered from low accuracy while classifying the different blood cell images and also consume higher processing power. The proposed model consists of two major steps such as segmentation and classification of peripheral blood cells. The modified local-information weighted intuitionistic Fuzzy C-means clustering (MLWIFCM)-based golden eagle optimization algorithm performs the nucleus segmentation. Finally, the peripheral blood cell classes such as Basophil, Lymphocyte, Neutrophil, Monocyte, and Eosinophil are effectively classified using hybrid-parameter RNN-based remora optimization algorithm. The MATLAB R2019b is used as the implementation platform. To analyze the performances of our proposed method, we have taken two datasets; they are BCCD and LISC datasets. Meanwhile, the classification performances were analyzed with the aid of different performance metrics such as mean accuracy, mean intersection over union, mean average precision, and mean BF score values. [ABSTRACT FROM AUTHOR]

White blood cells (leukocytes) are a very important component of the blood that forms the immune system, which is responsible for fighting foreign elements. The five types of white blood cells include neutrophils, eosinophils, lymphocytes, monocytes, and basophils, where each type constitutes a different proportion and performs specific functions. Being able to classify and, therefore, count these different constituents is critical for assessing the health of patients and infection risks. Generally, laboratory experiments are used for determining the type of a white blood cell. The staining process and manual evaluation of acquired images under the microscope are tedious and subject to human errors. Moreover, a major challenge is the unavailability of training data that cover the morphological variations of white blood cells so that trained classifiers can generalize well. As such, this paper investigates image transformation operations and generative adversarial networks (GAN) for data augmentation and state-of-the-art deep neural networks (i.e., VGG-16, ResNet, and DenseNet) for the classification of white blood cells into the five types. Furthermore, we explore initializing the DNNs' weights randomly or using weights pretrained on the CIFAR-100 dataset. In contrast to other works that require advanced image preprocessing and manual feature extraction before classification, our method works directly with the acquired images. The results of extensive experiments show that the proposed method can successfully classify white blood cells. The best DNN model, DenseNet-169, yields a validation accuracy of 98.8%. Particularly, we find that the proposed approach outperforms other methods that rely on sophisticated image processing and manual feature engineering. [ABSTRACT FROM AUTHOR]

Introduction: Allergen-specific IgE (sIgE) sensitization exists in a considerable fraction of chronic spontaneous urticaria (CSU) patients. Basophils have been implicated in the pathogenesis of CSU. This paper aimed to explore the relationship between allergic sensitization and basophil reactivity in CSU and the possible underlying mechanism. Methods: Basophil-enriched leukocytes were isolated from the peripheral blood of 76 CSU patients and 9 healthy controls. Basophil CD63 and FcεRIα (the alpha subunit of the high-affinity IgE receptor) expression in the blood samples with various house dust mite (HDM)-sIgE levels were determined by flow cytometry. Basophil reactivity and SHIP-1 (a molecule related to the IgE/FcεRI signaling pathway) expression were analyzed after stimulation with an HDM allergen or other stimuli. Results: HDM-sIgEstrong positive (≥3.5 kU/L) CSU patients had a significantly higher mean percentage of basophil CD63 and higher baseline levels of FcεRIα expressed by basophils than HDM-sIgEnormal (<0.35 kU/L) CSU patients and healthy controls; the same went for total serum IgE. After stimulation with Dermatophagoides pteronyssinus peptidase 1 (Derp1) alone or together with Derp1-sIgE, the stimulation index of CD63 and levels of FcεRIα expressed by basophils in HDM-sIgEstrong positive CSU patients were significantly higher than those in HDM-sIgEnormal CSU patients and healthy controls. Significantly more SHIP-1 mRNA expression in HDM-sIgEstrong positive CSU patients was induced after the combined stimulation in comparison to other subjects. Conclusion: CSU patients with higher HDM-sIgE levels (≥3.5 kU/L) may have higher CD63 and FcεRIα expression on peripheral blood basophils. Peripheral blood basophils in these CSU patients are more responsive to HDM allergen stimulation. Higher HDM-sIgE levels among CSU patients may implicate higher basophil reactivity. [ABSTRACT FROM AUTHOR]

The detection and classification of white blood cells (WBCs, also known as Leukocytes) is a hot issue because of its important applications in disease diagnosis. Nowadays the morphological analysis of blood cells is operated manually by skilled operators, which results in some drawbacks such as slowness of the analysis, a non-standard accuracy, and the dependence on the operator's skills. Although there have been many papers studying the detection of WBCs or classification of WBCs independently, few papers consider them together. This paper proposes an automatic detection and classification system for WBCs from peripheral blood images. It firstly proposes an algorithm to detect WBCs from the microscope images based on the simple relation of colors R, B and morphological operation. Then a granularity feature (pairwise rotation invariant co-occurrence local binary pattern, PRICoLBP feature) and SVM are applied to classify eosinophil and basophil from other WBCs firstly. Lastly, convolution neural networks are used to extract features in high level from WBCs automatically, and a random forest is applied to these features to recognize the other three kinds of WBCs: neutrophil, monocyte and lymphocyte. Some detection experiments on Cellavison database and ALL-IDB database show that our proposed detection method has better effect almost than iterative threshold method with less cost time, and some classification experiments show that our proposed classification method has better accuracy almost than some other methods. [ABSTRACT FROM AUTHOR]

The mast cells are initial effective lineage in both humoral and adaptive immunity. They are ubiquitous in skin, mucosa, and in function. They contain biologically essential and dynamic mediators in healthy and harmful conditions of tissue. Mast cell malfunctioning could be attributed to various chronic allergic diseases. Considerately, emerging evidence of mast cell involvement in various cancers shows them to have both positive and negative roles in tumour growth. It mostly indulges in tumour progression and metastasis via angiogenesis, extracellular matrix degradation, and mitogenic activity in the tumour microenvironment. The current paper reviewed research papers on mast cells in oral squamous cell carcinoma through the PubMed database from 1980 to the present date. The present paper is an attempt to summarise the research reports on the role of mast cells in oral squamous cell carcinoma. Further to this note, this paper also outlines the role of mast cells in normal physiological processes and tumour biology. [ABSTRACT FROM AUTHOR]

Background: Malakoplakia is characterized by the presence of plaques with macrophages containing inclusion bodies. The diagnosis of this disease is carried out by biopsy of the lesion. The objective of this paper was to assess the value of fresh urine sediment in the diagnosis of malakoplakia. Materials and Methods: Five suspected cases of malakoplakia that showed macrophages with inclusions called bodies of Michaelis-Gutmann (von Hansemann cells) in unstained urine sediment were processed with Papanicolaou, Giemsa, and periodic acid-Schiff (PAS) stains. Four of the five patients had a history of cystitis and had developed antibiotic resistance. The other patient had the characteristics cells in a routine urinalysis. Results: Papanicolaou stain revealed intracytoplasmic eosinophilic or basophilic bodies, single or multiple in macrophages. Such bodies were stained deep red with PAS technique. Giemsa stain showed these bodies with a faint basophilic coloration, sometimes with a central core. Bladder biopsies established the definitive diagnosis, showing bodies within and outside macrophages, with a concentric "birds-eye" or "owl-eye" (targetoid) appearance. Conclusions: Finding of von Hansemann cells in fresh urine sediment of patients with cystitis and a history of resistance to antibiotic scan leads to the diagnosis of malakoplakia. Giemsa stain can show in some cases the characteristic central core of Michaelis-Gutmann bodies. Malakoplakia is probably the result of an acquired defect in macrophage function causing impairment of bactericidal activity. A correct diagnosis is important because the spread to ureters with bilateral stenosis and obstruction can lead to kidney failure. [ABSTRACT FROM AUTHOR]

In this paper, the assessment is to investigate the effect of some synthetic glucocorticoid hormones (used frequently in therapy) on leukocytes (WBC and leukocyte formula), in rats. It is mentioned that the hormones used in this study (Prednisone, Dexamethasone and Betamethasone) have a large utilization in therapy due to the anti-inflammatory effect, overlooking in many cases the immunosuppressive effect. The determinations regarding the number of leukocytes and the leukocyte formula have been made using the IDEEX Analyzer, at the beginning and at the end of the experiment. As a result of the analysis it was revealed that the WBC%, at the end of the experiment, was higher, for all the experimental groups, comparing with the control group. After the interpretation of the obtained results regarding to the values of the leukocyte formula in the case of the experimental groups, it was shown increases of the percentages of neutrophils and basophils, decreases of percentages of eosinophils, lymphocytes and monocytes, comparing to the values obtained for the control group. [ABSTRACT FROM AUTHOR]

Oral food challenges remain the gold standard for the diagnosis of food allergy. Nevertheless, the allergy workup is based on the presence of a clinical history, which is evocative of an immune‐allergic reaction, and the first assessment is usually the performance of skin prick tests. Based on these results, allergists are used to evaluate the presence of serum‐specific IgE, which are today the most commonly prescribed in vitro test for the evaluation of a possible food allergy. Other in vitro tests include the basophil activation test, that is becoming more and more employed by clinicians and not only by researchers, and the evaluation of serum IgG4, which is still an issue of debate in the allergy community. The present paper reviews the use of these in vitro tests for the diagnosis of food allergy. [ABSTRACT FROM AUTHOR]

Epithelial mast cells are generally present in the airways of patients with allergic asthma that are inadequately controlled. Airway mast cells (MCs) are critically involved in allergic airway inflammation and contribute directly to the main symptoms of allergic patients. Phosphodiesterase 3 (PDE3) tailors signaling of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which are critical intracellular second messenger molecules in various signaling pathways. This paper investigates the pathophysiological role and disease-modifying effects of PDE3 in mouse bone marrow-derived MCs (bmMCs), human LAD2- and HMC1 mast cell lines, human blood basophils, and peripheral blood-derived primary human MCs (HuMCs). In a chronic house dust mite (HDM)-driven allergic airway inflammation mouse model, we observed that PDE3 deficiency or PDE3 inhibition (PDE3i) therapy reduced the numbers of epithelial MCs, when compared to control mice. Mouse bone marrow-derived MCs (bmMCs) and the human HMC1 and LAD2 cell lines predominantly expressed PDE3B and PDE4A. BmMCs from Pde3−/− mice showed reduced loss of the degranulation marker CD107b compared with wild-type BmMCs, when stimulated in an immunoglobulin E (IgE)-dependent manner. Following both IgE-mediated and substance P-mediated activation, PDE3i-pretreated basophils, LAD2 cells, and HuMCs, showed less degranulation than diluent controls, as measured by surface CD63 expression. MCs lacking PDE3 or treated with the PDE3i enoximone exhibited a lower calcium flux upon stimulation with ionomycine. In conclusion PDE3 plays a critical role in basophil and mast cell degranulation and therefore its inhibition may be a treatment option in allergic disease. [ABSTRACT FROM AUTHOR]

The pituitary gland is noted through distinct particularities to those of the other vertebrates. Within this class there are morphological variations in form, the size and lobulation of the pituitary gland. Thus, in some species, adenohypophysis is not anatomically divided but it is consisting of a single lobe. In many species of Teleostei adenohypophysis it consists of two lobes, one anterior or distally subdivided into two zones and the other intermediate. The present paper aims to highlight the structure of the pituitary gland and cell types present in cyprinids lobes. The studies were performed on microscopic preparations containing sagittal sections through carp pituitary. The sagittal histological sections made of 5µm reveal the presence of two distinct parts: neurohypophyses of nervous origin, and the adenohypophysis of epithelial origin. Considering the scientific importance and the practice of pituitary hormones in stimulating the maturation of gonads in fish also followed the changes of the pituitary structure, especially of the middle gonadotropic lobe. The histological study of the pituitary gland in the H. molitrix species at different times of the year has given us the possibility to track the seasonal variations of the basophil gonadotropic lobe structure. In the present study demonstrated that during the annual cycle, GTH cells go through different stages of activity that are not synchronous in all cells GTH. We were able to draw conclusions regarding the best period for harvesting pituitary glands used for pituitary injections under artificial reproduction conditions. [ABSTRACT FROM AUTHOR]

Regarding patient inclusion, in our study, all patients were diagnosed by positive skin test (ST) or DPT to amoxicillin (AX), and never based only on penicillin G positivity. Correspondence to "diagnosis of immediate reactions to amoxicillin: comparison of basophil activation markers CD63 and CD203c in a prospective study". [Extracted from the article]

Non-coding RNA expression has shown to have cell type-specificity. The regulatory characteristics of these molecules are impacted by changes in their expression levels. We performed next-generation sequencing and examined small RNA-seq data obtained from 6 different types of blood cells separated by fluorescence-activated cell sorting of severe COVID−19 patients and healthy control donors. In addition to examining the behavior of piRNA in the blood cells of severe SARS-CoV−2 infected patients, our aim was to present a distinct piRNA differential expression portrait for each separate cell type. We observed that depending on the type of cell, different sorted control cells (erythrocytes, monocytes, lymphocytes, eosinophils, basophils, and neutrophils) have altering piRNA expression patterns. After analyzing the expression of piRNAs in each set of sorted cells from patients with severe COVID−19, we observed 3 significantly elevated piRNAs - piR−33,123, piR−34,765, piR−43,768 and 9 downregulated piRNAs in erythrocytes. In lymphocytes, all 19 piRNAs were upregulated. Monocytes were presented with a larger amount of statistically significant piRNA, 5 upregulated (piR−49039 piR−31623, piR−37213, piR−44721, piR−44720) and 35 downregulated. It has been previously shown that piR−31,623 has been associated with respiratory syncytial virus infection, and taking in account the major role of piRNA in transposon silencing, we presume that the differential expression patterns which we observed could be a signal of indirect antiviral activity or a specific antiviral cell state. Additionally, in lymphocytes, all 19 piRNAs were upregulated. [ABSTRACT FROM AUTHOR]

In vitro cell activation through specific IgE bound to high-affinity receptors on the basophil surface is a widely used strategy for the evaluation of IgE-mediated immediate hypersensitivity reactions to betalactams. Cellular activation requires drug conjugation to a protein to form a large enough structure displaying a certain distance between haptens to allow the cross-linking of two IgE antibodies bound to the basophil's surface, triggering their degranulation. However, no information about the size and composition of these conjugates is available. Routine in vitro diagnosis using the basophil activation test uses free amoxicillin, which is assumed to conjugate to a carrier present in blood. To standardize the methodology, we propose the use of well-controlled and defined nanomaterials functionalized with amoxicilloyl. Silica nanoparticles decorated with PAMAM–dendrimer–amoxicilloyl conjugates (NpDeAXO) of different sizes and amoxicilloyl densities (50–300 µmol amoxicilloyl/gram nanoparticle) have been prepared and chemically characterized. Two methods of synthesis were performed to ensure reproducibility and stability. Their functional effect on basophils was measured using an in-house basophil activation test (BAT) that determines CD63+ or CD203chigh activation markers. It was observed that NpDeAXO nanocomposites are not only able to specifically activate basophils but also do so in a more effective way than free amoxicillin, pointing to a translational potential diagnosis. [ABSTRACT FROM AUTHOR]

The inadequate description of the clinics, together with the absence of a drug challenge, hinder to ascertain that the patients had experienced from a basophil-mediated hypersensitivity to a FQ. We have read with interest the paper by Loli-Ausejo and colleagues about the basophil activation test (BAT) in the diagnosis of hypersensitivity to fluoroquinolones (FQs).1 The authors report on a heterogeneous group of 19 patients who experienced a hypersensitivity reaction reported as immediate, accelerated/non-immediate or as unknown time of onset. Hypersensitivity to fluoroquinolones: the expression of basophil activation markers depends on the clinical entity and the culprit fluoroquinolone. [Extracted from the article]

Despite their rarity in peripheral blood, basophils play important roles in allergic disorders and other diseases including sepsis and COVID-19. Existing basophil isolation methods require many manual steps and suffer from significant variability in purity and recovery. We report an integrated basophil isolation device (i-BID) in microfluidics for negative immunomagnetic selection of basophils directly from 100 μL of whole blood within 10 minutes. We use a simulation-driven pipeline to design a magnetic separation module to apply an exponentially increasing magnetic force to capture magnetically tagged non-basophils flowing through a microtubing sandwiched between magnetic flux concentrators sweeping across a Halbach array. The exponential profile captures non-basophils effectively while preventing their excessive initial buildup causing clogging. The i-BID isolates basophils with a mean purity of 93.9% ± 3.6% and recovery of 95.6% ± 3.4% without causing basophil degradation or unintentional activation. Our i-BID has the potential to enable basophil-based point-of-care diagnostics such as rapid allergy assessment. [ABSTRACT FROM AUTHOR]

Granulocytes share the common feature of having a lobulated nucleus, a fact whose function has yet to be discussed in depth. This hypothesis suggests that the division of the nuclei follows an epigenetic purpose, separating genes into compartments with different regulatory mechanisms, which may be due to intrinsic factors like regulatory RNA or extrinsic factors like proteins. This paper describes the outlines of a line of research for both the initial testing to test the hypothesis and the following descriptive studies, including potential clinical uses in the prognosis or diagnosis of diseases that present dysregulation of the number of lobes. The chosen approach is to study the pattern of distribution (random or otherwise) of genes amongst the lobes. [ABSTRACT FROM AUTHOR]

Abstract: IgE and not IgG is usually associated with allergy. IgE lodged on mast cells in skin or gut and basophils in the blood allows for the prolonged duration of allergy through the persistent expression of high affinity IgE receptors. However, many allergic reactions are not dependent on IgE and are generated in the absence of allergen specific and even total IgE. Instead, IgG plasma cells are involved in induction of, and for much of the pathogenesis of, allergic diseases. The pattern of IgG producing plasma cells in atopic children and the tendency for direct or further class switching to IgE are the principle factors responsible for long‐lasting sensitization of mast cells in allergic children. Indirect class switching from IgG producing plasma cells has been shown to be the predominant pathway for production of IgE while a Th2 microenvironment, genetic predisposition, and the concentration and nature of allergens together act on IgG plasma cells in the atopic tendency to undergo further immunoglobulin gene recombination. The seminal involvement of IgG in allergy is further indicated by the principal role of IgG4 in the natural resolution of allergy and as the favourable immunological response to immunotherapy. This paper will look at allergy through the role of different antibodies than IgE and give current knowledge of the nature and role of IgG antibodies in the start, maintenance and resolution of allergy. [ABSTRACT FROM AUTHOR]

Upon first exposure to cetuximab, hypersensitivity reactions can occur. We aimed to assess the utility of the basophil activation test (BAT) to alpha-gal and cetuximab for predicting severe reactions. We prospectively recruited 38 patients and evaluated sIgE to alpha-gal in all patients before the first application of cetuximab. In all alpha-gal-sensitized patients, we evaluated skin tests to meat extracts, gelatine, and cetuximab and performed BAT with alpha-gal and cetuximab. In 24% (9/38) of patients, sIgE to alpha-gal was >0.10 kUA/L, and 8/9 reacted to the cetuximab. Basophil activation tests with alpha-gal were positive in all sensitized patients and were higher in those with severe reactions (18.3% in grade 4 [n = 4] vs. 1.8% in grade 2 [n = 3] or no reaction [n = 1] at 3.3 ng/mL of alpha-gal; p = 0.03). All patients with severe grade 4 reactions had a positive CD63 BAT response to cetuximab compared to patients with moderate or no reaction, who all had negative BAT (57.7% vs. 0.9% at 500 µg/mL, 63.2% vs. 4.1% at 100 µg/mL, 58.2% vs. 2.7% at 10 µg/mL, and 32.1% vs. 3.3% at 1 µg/mL of cetuximab, respectively; p ≤ 0.001). In summary, before initiating cetuximab treatment, sIgE to alpha-gal should be assessed in all patients. To predict the severity of the reaction and to assess the risk of cetuximab-induced anaphylaxis, we should perform BATs with alpha-gal or more discriminative BATs with cetuximab. [ABSTRACT FROM AUTHOR]

In Australia, neuromuscular blocking agents are the leading cause of perioperative anaphylaxis. Current investigation of suspected anaphylaxis includes tryptase levels, serum immunoglobulin E (IgE) levels, and skin testing, including intradermal testing and skin prick testing. The gold standard for the diagnosis of a hypersensitivity reaction is a challenge test, but this poses a risk to patient safety. An alternative test, known as the basophil activation test (BAT) is a form of cellular in vitro testing using flow cytometry to measure the degree of basophil degranulation within a sample of blood following exposure to an allergen. This acts as a surrogate marker for mast cell and basophil activation, thereby identifying IgE-mediated allergy. It is most commonly used to supplement equivocal findings from initial in vitro testing to assist in confirming the diagnosis of a hypersensitivity reaction and identify the causative agent. We present a case series in which five patients with suspected anaphylaxis underwent a BAT, demonstrating its role and limitations in allergy testing within Australia. [ABSTRACT FROM AUTHOR]

Background: The introduction of biological drugs in the management of chronic rhinosinusitis with nasal polyps (CRSwNP) is allowing new and increasingly promising therapeutic options. This manuscript aims to provide a multicenter trial in a real-life setting on Mepolizumab treatment for severe uncontrolled CRSwNP with or without comorbid asthma. Methods: A retrospective data analysis was jointly conducted at the Otolaryngology–Head and Neck Surgery departments of La Sapienza University and San Camillo Forlanini Hospital in Rome. Both institutions participated by sharing clinical information on patients with CRSwNP treated with Mepolizumab. Patients were evaluated before starting Mepolizumab, at six months and at twelve months from the first drug administration. During follow–up visits, patients underwent endoscopic evaluation, quality of life assessment, nasal symptoms assessment, and blood tests to monitor mainly neutrophils, basophils, eosinophils, and IgG, IgA, and IgE assay. Results: Twenty patients affected by CRSwNP and treated with Mepolizumab were enrolled (12 females and 8 males with a mean age of 63.7 years). Sixteen patients (80%) had concomitant asthma. During follow-up, a gradual improvement in nasal polyp score, quality of life and nasal symptoms, assessed by SNOT-22 and VAS and loss of smell measured by olfactory VAS, was found. Regarding blood tests, eosinophils decreased gradually, while other blood parameters showed no statistically significant changes. Conclusions: Mepolizumab has been shown to be effective in the therapeutic management of patients with CRSwNP. Further studies are needed to support our findings and better understand the underlying immune pathways to predict patients' response to biological treatment in CRSwNP. [ABSTRACT FROM AUTHOR]

Acute promyelocytic leukemia is a rare form of acute myeloid leukemia in which immature promyelocytes abnormally proliferate in the bone marrow. In most cases, the disease is characterised by the translocation t(15;17) (q24;q21), which causes the formation of PML::RARA, an oncogenic fusion protein responsible for blocking myeloid differentiation and survival advantage. Here, we present a case of acute promyelocytic leukemia with two unusual features: basophilic differentiation and a three-way translocation involving chromosomes 12, 15 and 17. In the few cases reported, basophilic differentiation was associated with a poor prognosis. In contrast, our patient responded promptly to the standard treatment with all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) and obtained complete remission. To our knowledge, this is the first report of basophilic acute promyelocytic leukemia with the three-way translocation t(12;17;15) (p13; q24;q21). [ABSTRACT FROM AUTHOR]

Background: The basophil activation test is an emerging clinical tool in the diagnosis of cow's milk allergy (CMA). The aim was to assess the association between the basophil allergen threshold sensitivity to the major milk protein casein (casein‐specific CD‐sens), the levels of milk‐ and casein‐specific Immunoglobulin E antibodies (IgE‐ab), and the severity of allergic reactions at milk challenges. Methods: We enrolled 34 patients aged 5–15 (median 9) years who underwent a double‐blind placebo‐controlled milk‐challenge (DBPCMC) as screening before inclusion in an oral immunotherapy study for CMA. The severity of the allergic reaction at the DBPCMC was graded using Sampson's severity score. Venous blood was drawn before the DBPCMC. Milk‐ and casein‐specific IgE‐ab were analyzed. Following in vitro stimulation of basophils with casein, casein‐specific CD‐sens, was determined. Results: Thirty‐three patients completed the DBPCMC. There were strong correlations between casein‐specific CD‐sens and IgE‐ab to milk (rs = 0.682, p <.001), and between casein‐specific CD‐sens and IgE‐ab to casein (rs = 0.823, p <.001). There was a correlation between the severity of the allergic reaction and casein‐specific CD‐sens level (rs = 0.395, p =.041) and an inverse correlation between casein‐specific CD‐sens level and the cumulative dose of milk protein to which the patient reacted at the DBPCMC (rs = −0.418, p =.027). Among the 30 patients with an allergic reaction at the DBPCMC, 67% had positive casein‐specific CD‐sens, 23% had negative casein‐specific CD‐sens, and 10% were declared non‐responders. Conclusion: Two thirds of those reacting at the DBPMC had positive casein‐specific CD‐sens, but reactions also occurred despite negative casein‐specific CD‐sens. The association between casein‐specific CD‐sens and the severity of the allergic reaction and cumulative dose of milk protein, respectively, was moderate. [ABSTRACT FROM AUTHOR]

This review article acknowledges the pioneering contribution of William Bate Hardy in shaping the concept of mast cell heterogeneity. In two outstanding papers, published in 1894 and 1895, he focussed on the ‘wandering cells’ (the modern leucocytes) in different mammalian species and distinguished two types of granular basophil cells, i.e., the coarsely granular basophil cells and the splanchnic basophil cells. These corresponded to the populations of connective tissue-type and mucosal mast cells, respectively, described 70 years later by Enerbäck in rodents. Among the coarsely granular basophil cells, he also differentiated those cells which populated the serosal cavities – the so-called coelomic coarsely granular basophil cells – from the common coarsely granular basophil cells, which were localized in the connective tissues. He stated that the granular basophil cells presented with different morphological and histochemical characteristics in diverse animal species as well as at different anatomical sites. Remarkably, he performed a series of functional experiments on the basophil cells as well as the other wandering cells, and suggested the view that different granular basophil cells might express functional specializations. [ABSTRACT FROM AUTHOR]

Background: Idiopathic non-histaminergic acquired angioedema (InH-AAE) is a rare disease for which there are no available laboratory parameters to clearly define the disorder. Therapy is often difficult and various treatment options have been proposed. In this paper, we have evaluated the most effective therapies for InH-AAE on the basis of current literature and report the therapeutic effect of omalizumab in three patients with InH-AAE. Methods: Literature was searched with a combination of MeSH/EMTREE terms and freetext search for angioedema and therapy/omalizumab in the databases Medline (Ovid), PubMed/Premedline, Embase, Cochrane library and Scopus with no time or language restrictions. In three patients affected by InH-AAE the therapeutic effect of omalizumab was demonstrated by clinical outcome. In one patient the FcεRI receptor density on basophils was monitored under therapy with omalizumab. Results: From the review of the current literature, 25 out of 286 publications dealing with relevant therapeutic recommendations for InH-AAE were analyzed. Six publications with 98 patients referred to tranexamic acid, of which 27 had a complete, 70 a partial and 1 no response. In three case reports ecallantide showed 2 patients with a complete and 1 a partial response. In four case reports for Icatibant 2 had a complete and 3 a partial response. When evaluated in three reports, C1-INH found complete and partial responses in 2 patients each. One patient had a complete response to progestin. Omalizumab was described in 6 reports with 20 patients, all of whom showed a complete response. All three patients described in our study responded to omalizumab with a complete remission. Density of FcεRI receptors on basophils, monitored in patient 1 on a long-term course of 31 months, decreased from 74,051.61 to a minimal level of 1907 receptors per cell. Conclusions: Omalizumab seems to be the most effective therapy in InH-AAE. The continuous decrease of FcεRI-receptor density on basophils under therapy with omalizumab along with clinical improvement observed in one patient, could serve as a new approach for further studies to evaluate FcεRI-receptor density as a surrogate marker for therapeutic efficacy and for dosing and determining injection intervals of omalizumab. Trial registration BASEC-Nr. Req-2016-00692. Retrospectively registered 24.11.2016. [ABSTRACT FROM AUTHOR]

Background: Flow cytometry-based basophil activation tests (BAT) have been performed with various modifications, differing in the use of distinct identification and activation markers. Established tests use liquid reagents while a new development involves the use of tubes with dried antibody reagents. The aim of this pilot study was to compare these two techniques in patients with insect venom allergy. Methods: Seventeen patients with an insect venom allergy were included in the study. The established "BAT 1" utilizes conventional antibody solutions of anti-CCR3 for basophil identification and anti-CD63 to assess basophil activation, whereas "BAT 2" uses dried anti-CD45, anti-CD3, anti-CRTH2, anti-203c and anti-CD63 for identification and activation measurement of basophils. Negative and positive controls as well as incubations with honey bee venom and yellow jacket venom at three concentrations were performed. Results: Seven patients had to be excluded due to low basophil counts, high values in negative controls or negative positive controls. For the remaining 10 patients the overall mean (± SD) difference in activated basophils between the two tests was 0.2 (± 12.2) %P. In a Bland-Altman plot, the limit of agreement (LoA) ranged from 24.0 to -23.7. In the qualitative evaluation (value below/above cut-off) Cohen's kappa was 0.77 indicating substantial agreement. BAT 2 took longer to perform than BAT 1 and was more expensive. Conclusion: The BAT 2 technique represents an interesting innovation, however, it was found to be less suitable compared to an established BAT for the routine diagnosis of insect venom allergies. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by anti-nuclear autoantibodies whose production is promoted by autoreactive T follicular helper (TFH) cells. During SLE pathogenesis, basophils accumulate in secondary lymphoid organs (SLO), amplify autoantibody production and disease progression through mechanisms that remain to be defined. Here, we provide evidence for a direct functional relationship between TFH cells and basophils during lupus pathogenesis, both in humans and mice. PD-L1 upregulation on basophils and IL-4 production are associated with TFH and TFH2 cell expansions and with disease activity. Pathogenic TFH cell accumulation, maintenance, and function in SLO were dependent on PD-L1 and IL-4 in basophils, which induced a transcriptional program allowing TFH2 cell differentiation and function. Our study establishes a direct mechanistic link between basophils and TFH cells in SLE that promotes autoantibody production and lupus nephritis. Basophils have been implicated in systemic lupus erythematosus (SLE), as evidenced by the fact that basophil-deficient mice do not develop the disease. Here, the authors demonstrate that PD-L1 and IL-4 expression in basophils promotes the pathogenic accumulation of follicular helper T cells in patients with SLE and murine models. [ABSTRACT FROM AUTHOR]

Drug hypersensitivity reactions (DHRs) to platinum-based compounds (PCs) are on the rise, and their personalized and safe management is essential to enable first-line treatment for these cancer patients. This study aimed to evaluate the usefulness of the basophil activation test by flow cytometry (BAT-FC) and the newly developed sIgE-microarray and BAT-microarray in diagnosing IgE-mediated hypersensitivity reactions to PCs. A total of 24 patients with DHRs to PCs (20 oxaliplatin and four carboplatin) were evaluated: thirteen patients were diagnosed as allergic with positive skin tests (STs) or drug provocation tests (DPTs), six patients were diagnosed as non-allergic with negative STs and DPTs, and five patients were classified as suspected allergic because DPTs could not be performed. In addition, four carboplatin-tolerant patients were included as controls. The BAT-FC was positive in 2 of 13 allergic patients, with a sensitivity of 15.4% and specificity of 100%. However, the sIgE- and BAT-microarray were positive in 11 of 13 DHR patients, giving a sensitivity of over 84.6% and a specificity of 90%. Except for one patient, all samples from the non-allergic and control groups were negative for sIgE- and BAT-microarray. Our experience indicated that the sIgE- and BAT-microarray could be helpful in the endophenotyping of IgE-mediated hypersensitivity reactions to PCs and may provide an advance in decision making for drug provocation testing. [ABSTRACT FROM AUTHOR]

Different inflammatory endotypes reflect the heterogeneity of chronic rhinosinusitis with nasal polyps' (CRSwNPs) clinical presentation. This retrospective study aimed to analyze the distribution of polyps in nasal cavities and paranasal sinuses to establish a possible association between CRSwNP endotypes, prognosis, and polyps' extension. This study included 449 adult patients who underwent endoscopic sinus surgery for CRSwNPs between 2009 and 2022. Patients were categorized based on the number of paranasal sinuses involved by polyps. Statistical analyses, including Cox regression, were performed to identify associations between demographic, clinical, and histopathological factors and disease recurrence. CRSwNP patients were stratified into four groups based on the extent of polyp involvement. Asthma and acetylsalicylic acid (ASA) sensitivity were associated with more sinuses involved (p-values = 0.0003 and 0.0037, respectively). Blood eosinophil counts increased with the number of sinuses affected (p-value < 0.0001). The distribution of eosinophilic and non-eosinophilic histotypes varied significantly among these groups (p-value < 0.0001). The risk of CRSwNP recurrence was higher in patients with asthma, higher basophil percentages, and eosinophilic histotype (p-value 0.0104, 0.0001, 0.0118, and 0.0104, respectively). This study suggests a positive association between the number of paranasal sinuses involved by polyps and the severity of CRSwNPs, particularly in patients with eosinophilic histotype, asthma, and ASA sensitivity. [ABSTRACT FROM AUTHOR]

It is estimated that allergies afflict up to 40% of the world's population. A primary mediator for allergies is the aggregation of antigens and IgE antibodies bound to cell-surface receptors, FcεRI. Antibody/antigen aggregate formation causes stimulation of mast cells and basophils, initiating cellular degranulation and releasing immune mediators which produce an allergic or anaphylactic response. Understanding the shape and structure of these aggregates can provide critical insights into the allergic response. We have previously developed methods to geometrically model, simulate and analyze antibody aggregation inspired by rigid body robotic motion simulations. Our technique handles the large size and number of molecules involved in aggregation, providing an advantage over traditional simulations such as molecular dynamics (MD) and coarse-grained energetic models. In this paper, we study the impact of model resolution on simulations of geometric structures using both our previously developed Monte Carlo simulation and a novel application of rule-based modeling. These methods complement each other, the former providing explicit geometric detail and the latter providing a generic representation where multiple resolutions can be captured. Our exploration is focused on two antigens, a man-made antigen with three binding sites, DF3, and a common shrimp allergen (antigen), Pen a 1. We find that impact of resolution is minimal for DF3, a small globular antigen, but has a larger impact on Pen a 1, a rod-shaped molecule. The volume reduction caused by the loss in resolution allows more binding site accessibility, which can be quantified using a rule-based model with implicit geometric input. Clustering analysis of our simulation shows good correlation when compared with available experimental results. Moreover, collisions in all-atom reconstructions are negligible, at around 0.2% at 90% reduction. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

A major problem in SARS-CoV-2-infected patients is the massive tissue inflammation in certain target organs, including the lungs. Mast cells (MC), basophils (BA), and eosinophils (EO) are key effector cells in inflammatory processes. These cells have recently been implicated in the pathogenesis of SARS-CoV-2 infections. We explored coronavirus receptor (CoV-R) expression profiles in primary human MC, BA, and EO, and in related cell lines (HMC-1, ROSA, MCPV-1, KU812, and EOL-1). As determined using flow cytometry, primary MC, BA, and EO, and their corresponding cell lines, displayed the CoV-R CD13 and CD147. Primary skin MC and BA, as well as EOL-1 cells, also displayed CD26, whereas primary EO and the MC and BA cell lines failed to express CD26. As assessed using qPCR, most cell lines expressed transcripts for CD13, CD147, and ABL2, whereas ACE2 mRNA was not detectable, and CD26 mRNA was only identified in EOL-1 cells. We also screened for drug effects on CoV-R expression. However, dexamethasone, vitamin D, and hydroxychloroquine did not exert substantial effects on the expression of CD13, CD26, or CD147 in the cells. Together, MC, BA, and EO express distinct CoV-R profiles. Whether these receptors mediate virus–cell interactions and thereby virus-induced inflammation remains unknown at present. [ABSTRACT FROM AUTHOR]

Background: Immunological abnormalities are implicated in the pathogenesis of many chronic diseases. Due to the drug-related adverse effects of currently available orthodox immunomodulators, natural immunomodulators are being looked upon as potential agents to replace them in therapeutic regimens. This research aimed to investigate the immunomodulatory potential of L. micranthus extracts epiphytic on Psidium guajava (LMPGE) and Parkia biglobosa (LMPBE). Methods: Phytochemical screening and acute toxicity testing were carried out to identify the phytoconstituents and safety profiles of the extracts. The extracts' innate and adaptive immunomodulatory potentials were determined in experimental animals using in vivo leucocyte mobilization, delayed-type hypersensitivity (DTH) response, hemagglutination antibody titre, and cyclophosphamide-induced myelosuppression models. Levamisole was used as the standard drug throughout the study. Results: Compared to LMPBE, LMPGE contained significantly (p < 0.05) more tannins, cyanogenic glycosides, saponins, reducing sugars, glycosides, flavonoids, and alkaloids. Furthermore, the groups treated with the extracts had a significant (p < 0.05) increase in the total number of leucocytes, neutrophils, basophils, and antibody titers relative to the untreated control. In the same way, the treatment raised TLC in cyclophosphamide-intoxicated rats, with 250 mg/kg b. w. of LMPGE and LMPBE recording 9712.50 ± 178.00 and 8000.00 ± 105.00 × 109 /L, respectively, compared to 3425.00 ± 2 5.00 × 109 /L in the untreated group. Overall, LMPGE was more effective. Conclusions: The findings from this study suggest that L. micranthus epiphytic in Psidium guajava and Parkia biglobosa has possible immune stimulating potential. [ABSTRACT FROM AUTHOR]

Introduction: Revealing the responsible mechanisms of hypersensitivity reactions (HSRs) to chemotherapeutics may guide the prevention of these reactions and provide re-use of the responsible drug. Aim: To evaluate the role of basophils during the immediate-type HSRs and desensitization to culprit chemotherapeutics. Material and methods: Twenty patients were included in the study. Peripheral whole blood samples were obtained from patients immediately after the reaction and pre- and post- desensitization procedures in the next cycle. Basophil activation was assessed by flow cytometry. A stimulation index (SI) was calculated by proportioning the values at the time of reaction and post-desensitization to the pre-desensitization values. Results: Desensitization with the culprit chemotherapeutic was performed in 14 of 20 patients. The culprit drug was cisplatin in 4 patients, taxanes in 5 and etoposide in 5 patients. In patients who had HSRs to cisplatin and etoposide (except one with etoposide hypersensitivity), reaction time SI was greater than 2, indicating basophil activation. In a patient who had a breakthrough reaction to cisplatin during desensitization, basophil activation was also detected at the time of this reaction. None of the patients with taxane hypersensitivity reaction showed basophil activation at the time of the reaction. Post-desensitization basophil activation was not detected in any patient. There was a significant tryptase increment during the index reaction in all cisplatin patients, only one taxane patient, and during the breakthrough reaction to cisplatin. Conclusions: Basophil activation has been shown to play a role in the mechanism of immediate-type HSRs to cisplatin and etoposide. Desensitization procedures in this group of patients prevent basophil activation and ensure the safe use of the drug. [ABSTRACT FROM AUTHOR]

The current investigation aims to study certain parameters including, IL-17A, creatinine, lymphocyte, and basophile in patients who suffer from SLE renal failure for comparing them with healthy control groups. The study was done on 105 patients (35 males, 70 females) who are confirmed to have SLE in Thi-Qar Province, southern of Iraq. The researchers withdraw 5ml of venous blood from 50 healthy control group to conduct three tests; immune tests to find out the amount of IL-17A (ELISA), biochemical tests to find out the amount of creatinine (colorimetric method), and CBC tests to find out the number of lymphocytes and basophils. The findings revealed that the total SLE illness rate was 83%, with females having a higher infection rate (66.67%) than males (33.33%). Significant variations were identified between sexes. Moreover, it is shown that there is a considerable increase in the level of IL17A and the amount of creatinine which was higher than those of healthy control. Finally, it is demonstrated that females suffer from this disease in age of 13-45 more than males. Compared to healthy group, the level of IL -17A and the creatinine were increased in some patients whereas the lymphocyte and basophile were decreased in some others. Thus, it is concluded that the level of IL17A, creatinine, lymphocyte, and basophie play a fundamental role in the SLE Pathogeneses. [ABSTRACT FROM AUTHOR]

Simple Summary: Anaphylaxis to paclitaxel requires desensitization protocols for safe drug re-administration. Hypersensitivity severity and skin tests (STs) guide desensitization protocol choices. The only study reporting on the basophil activation test (BAT) in diagnosing hypersensitivity to paclitaxel showed unsatisfactory diagnostic performance. Here, we present a modified BAT that shows unprecedented sensitivity (90.91%) and specificity (90.91%) in diagnosing hypersensitivity to paclitaxel and demonstrate that most patients with hypersensitivity to paclitaxel who score ST-negative score BAT-positive. We propose that the present BAT should be used to personalize patient management. Moreover, we predict the interactions of paclitaxel with the degranulation-competent MRGPRX2 receptor using an in silico molecular docking study. Immediate hypersensitivity reactions (iHSRs) to taxanes are observed in 6% and 4% of gynecologic and breast cancer patients, respectively. Drug desensitization is the only option, as no comparable alternative therapy is available. Surfactants in the taxane formulation have been implicated in the immunopathogenesis of iHSRs, although sporadic skin test (ST) positivity and iHSRs to nab-paclitaxel have suggested the involvement of the taxane moiety and/or IgE-mediated pathomechanisms. In vitro diagnostic tests might offer insights into mechanisms underlying iHSRs to taxanes. The aim of the present study was to address this unmet need by developing a novel basophil activation test (BAT). The study included patients (n = 31) undergoing paclitaxel/carboplatin therapy. Seventeen patients presented with iHSRs to paclitaxel (iHSR-Taxpos), and eleven were tolerant (iHSR-Taxneg). Fourteen patients presented with iHSRs to carboplatin (iHSR-Plpos), and fourteen were tolerant (iHSR-Plneg). The BAT median stimulation index (SI) values were 1.563 (range, 0.02–4.11; n = 11) and −0.28 (range −4.88–0.07, n = 11) in iHSR-Taxpos and iHSR-Taxneg, respectively. The BAT median SI values were 4.45 (range, 0.1–26.7; n = 14) and 0 (range, −0.51–1.65; n = 12) in iHSR-Plpos and iHSR-Plneg, respectively. SI levels were not associated with iHSR severity grading. Comparing BAT results in iHSR-Taxpos and iHSR-Taxneg showed the area under the receiver operator characteristic (ROC) curve to be 0.9752 (p = 0.0002). The cutoff calculated by the maximized likelihood ratio identified 90.91% of iHSR-Taxpos patients and 90.91% of iHSR-Taxneg patients. Comparing BAT results for iHSR-Plpos and iHSR-Plneg showed the area under the ROC curve to be 0.9286 (p = 0.0002). The cutoff calculated by the maximized likelihood ratio identified 78.57% of iHSR-Plpos patients and 91.67% of iHSR-Plneg patients. Most iHSR-Taxpos patients for which ST was available (10/11) scored ST-negative and BAT-positive, whereas most iHSR-Plpos patients for which ST was available (14/14) scored both BAT- and ST-positive. This suggested the intervention of non-IgE-mediated mechanisms in iHSR-Taxpos patients. Consistent with this view, an in silico molecular docking analysis predicted the high affinity of paclitaxel to the degranulation-competent MRGPRX2 receptor. This hypothesis warrants further in vitro investigations. In conclusion, the present study provides preliminary proof-of-concept evidence that this novel BAT has potential utility in understanding mechanisms underlying iHSRs to taxanes. [ABSTRACT FROM AUTHOR]

Due to the scale of the phenomenon, food allergy constitute a significant health problem and significantly impair the quality of life of patients. Differential diagnostics, including skin tests, sIgE detection tests, basophil and mast cell activation tests as well as double-blind placebo-controlled food challenge tests, is the gold standard in the diagnosis of food allergy. Recently, increasing attention has been paid to the potential use of nasal provocation test in the diagnosis of food allergy. Allergen dose, protocol standardization, assessment of subjective complaints and objectivization of test results are important factors determining the applicability of provocation tests. [ABSTRACT FROM AUTHOR]

Objective: Allergic rhinitis is a chronic upper respiratory disease characterized by inflammation of the nose due to the accumulation of inflammatory cells. We aimed to investigate the therapeutic efficacy of capsaicin and/or steroids in reducing the symptoms, proinflammatory cytokine levels, and inflammatory cell infiltrations in an animal model of allergic rhinitis. Materials and Methods: Thirty-five male Wistar rats were divided into five groups. Following injection and initial intranasal challenge with ovalbumin, rats were treated with intraperitoneal capsaicin (50 mg/kg) and/or steroid (10 mg/kg) injection for seven days. After nasal symptom scorings, all rats were sacrificed under anesthesia, and blood samples and nasal septa were collected for hematologic, biochemical, and histopathologic examinations. Results: The ovalbumin challenge increased nasal symptom scores, eosinophil and basophil counts, the serum IL-4, IL-5, IL-13 and IL- 33 levels, and histopathologic damage. Capsaicin and/or steroid administration attenuated the allergic rhinitis symptoms. There was a therapeutic effect of capsaicin and the combined use of capsaicin and steroids on experimentally-induced allergic rhinitis as reflected by decreases in allergic inflammation and secretion of cytokines. There was no difference between the CAPS, CAPS-STR, and STR groups in terms of allergic rhinitis symptoms. Conclusion: Parenteral administration of CAPS alone, and especially the combined use of CAPS and STR, effectively treats allergic rhinitis symptoms in a rat model of allergic rhinitis. Our results show that CAPS alone is not an effective alternative to STR but accelerates the recovery of allergic rhinitis. [ABSTRACT FROM AUTHOR]

Qingkailing injection (QKLI) is a kind of multi-component traditional Chinese medicine injection. It has been widely used in clinical practice, but in recent years, it has caused more and more adverse reactions, mainly manifested as pseudo-allergic symptoms. To explore the potential mechanism of the pseudo-allergic reaction by QKLI, basophilic leukemia cell line 2H3 (RBL-2H3) was chosen. The results showed that QKLI at doses of 5, 10 and 20 mL L−1 activated phosphoinositide 3-kinase (PI3K) activity and also increased the levels of Ras-related C3 botulinum toxin substrate 1 (Rac1), p21 protein-activated kinase 1 (Pak1), LIM kinase (Limk1) and cofilin (an actin polymerization regulator) proteins. What's more, QKLI aggravated the depolymerization of F-actin. NSC23766, a Rac1 inhibitor, reversed the previous results in QKLI-treated RBL-2H3 cells. In addition, when the Rac1 gene was knocked down using lentiviral vector-loaded shRNA in RBL-2H3 cells, the PI3K activity and depolymerization of F-actin were downregulated, hinting that the pseudo-allergic reaction was significantly reduced. In general, the pseudo-allergic reaction induced by QKLI was likely to be based on PI3K-Rac1 signaling pathways partially. [ABSTRACT FROM AUTHOR]

Highlights • Transfer learning approaches are employed to build a complete identification system for white blood cells (WBCs) in blood smear image. • A complete end-to-end CNN architecture is proposed to identify the different WBCs types (basophil, eosinophil, lymphocyte, monocyte and neutrophil). • The proposed CNN architecture (WBCsNet) is the first deep learning architecture for WBCs identification which achieved a higher classification accuracy more than the traditional WBCs identification systems or even the transfer learning approaches. • The proposed WBCsNet is re-employed as a pre-trained network and achieves high accuracy scores for classifying limited balanced dataset. • We present features visualization for the WBCsNet activation which reflect higher reasonable response than the pre-trained activated one. Abstract Background and objectives White blood cells (WBCs) differential counting yields valued information about human health and disease. The current developed automated cell morphology equipments perform differential count which is based on blood smear image analysis. Previous identification systems for WBCs consist of successive dependent stages; pre-processing, segmentation, feature extraction, feature selection, and classification. There is a real need to employ deep learning methodologies so that the performance of previous WBCs identification systems can be increased. Classifying small limited datasets through deep learning systems is a major challenge and should be investigated. Methods In this paper, we propose a novel identification system for WBCs based on deep convolutional neural networks. Two methodologies based on transfer learning are followed: transfer learning based on deep activation features and fine-tuning of existed deep networks. Deep acrivation featues are extracted from several pre-trained networks and employed in a traditional identification system. Moreover, a novel end-to-end convolutional deep architecture called "WBCsNet" is proposed and built from scratch. Finally, a limited balanced WBCs dataset classification is performed through the WBCsNet as a pre-trained network. Results During our experiments, three different public WBCs datasets (2551 images) have been used which contain 5 healthy WBCs types. The overall system accuracy achieved by the proposed WBCsNet is (96.1%) which is more than different transfer learning approaches or even the previous traditional identification system. We also present features visualization for the WBCsNet activation which reflects higher response than the pre-trained activated one. Conclusion a novel WBCs identification system based on deep learning theory is proposed and a high performance WBCsNet can be employed as a pre-trained network. Graphical abstract Image, graphical abstract [ABSTRACT FROM AUTHOR]

This paper examines the activation and inhibition of activation of human basophils. After a brief description of human basophils, different methods to determine basophil activation are discussed with a special emphasis on the use of flow cytometric methods, as these circumvent the potential problems of assays based on the loss of colour by activated basophils. The activation of human basophils by ultra-high dilutions of anti-IgE is discussed. The majority of the paper describes the inhibition of basophil activation by ultra-high dilutions of histamine. The results from published papers are described and discussed. After over 20 years research trying to find out if high dilutions of histamine have a negative feedback effect on the activation of basophils by anti-IgE, what do we know? The methods are poorly standardized between laboratories – although the same is true for conventional studies. Certainly there appears to be some evidence for an effect – albeit small in some cases – with the high dilutions in several different laboratories using the flow cytometric methodologies. After standardization of a number of parameters, it is recommended that a multi-centre trial be performed to hopefully put an end to this “never-ending story”. [Copyright &y& Elsevier]