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Frontiers in Immunology 2022Urticaria is a symptom of acute skin allergies that is not clearly understood, but mast cell histamine is hypothesized to cause swelling and itching. Omalizumab, an... (Review)
Review
Urticaria is a symptom of acute skin allergies that is not clearly understood, but mast cell histamine is hypothesized to cause swelling and itching. Omalizumab, an anti-human IgE antibody that traps IgE and prevents its binding to high-affinity IgE receptors, is effective in treating urticaria. We recently experienced a case of urticaria refractory to antihistamine therapy in which the peripheral-blood basophil count responded to omalizumab therapy and its withdrawal. Furthermore, the peripheral-blood basophils showed an unexpected increase in the expression of a cell surface activation marker. This phenomenon has been reported by other analyses of basophil and mast cell dynamics during omalizumab treatment. Here, we analyze these observations and formulate a hypothesis for the role of basophils in urticaria. Specifically, that activated basophils migrate to the local skin area, lowering peripheral-blood counts, omalizumab therapy alters basophilic activity and causes their stay in the peripheral blood. We hope that our analysis will focus urticaria research on basophils and reveal new aspects of its pathogenesis.
Topics: Anti-Allergic Agents; Basophils; Humans; Immunoglobulin E; Omalizumab; Urticaria
PubMed: 35663949
DOI: 10.3389/fimmu.2022.883692 -
Cancers Jan 2021Interactions between malignant cells and neighboring stromal and immune cells profoundly shape cancer progression. New forms of therapies targeting these cells have... (Review)
Review
Interactions between malignant cells and neighboring stromal and immune cells profoundly shape cancer progression. New forms of therapies targeting these cells have revolutionized the treatment of cancer. However, in order to specifically address each population, it was essential to identify and understand their individual roles in interaction between malignant cells, and the formation of the tumor microenvironment (TME). In this review, we focus on the myeloid cell compartment, a prominent, and heterogeneous group populating TME, which can initially exert an anti-tumoral effect, but with time actively participate in disease progression. Macrophages, dendritic cells, neutrophils, myeloid-derived suppressor cells, mast cells, eosinophils, and basophils act alone or in concert to shape tumor cells resistance through cellular interaction and/or release of soluble factors favoring survival, proliferation, and migration of tumor cells, but also immune-escape and therapy resistance.
PubMed: 33418996
DOI: 10.3390/cancers13020165 -
Journal of Immunology (Baltimore, Md. :... Jan 2022This Brief Review delves into B cell responses in the context of allergy. The primary contribution of B cells to allergy is the production of IgE, the Ab isotype that... (Review)
Review
This Brief Review delves into B cell responses in the context of allergy. The primary contribution of B cells to allergy is the production of IgE, the Ab isotype that triggers immediate hypersensitivity reactions through the release of mediators from mast cells and basophils. B cells may also have protective roles in allergy, such as through the production of IgG or as regulatory B cells. In this review, I focus on the basic principles of B cell differentiation and discuss features relevant to allergic immune responses. In particular, I discuss: (1) class-switch recombination; (2) plasma cell differentiation; (3) germinal centers and affinity maturation; and (4) memory B cells and recall responses, with an emphasis on IgE, IgG1, and IgG4. I also consider how B cells may contribute to allergic responses independent of Ab production-for example, by serving as APCs.
Topics: B-Lymphocytes; B-Lymphocytes, Regulatory; Basophils; Cell Differentiation; Germinal Center; Humans; Hypersensitivity, Immediate; Immunoglobulin A; Immunoglobulin Class Switching; Immunoglobulin E; Immunoglobulin G; Immunologic Memory; Lymphocyte Activation; Mast Cells; Memory B Cells; Plasma Cells
PubMed: 35017215
DOI: 10.4049/jimmunol.2100988 -
Antibodies (Basel, Switzerland) Oct 2020Immunoglobulin E (IgE) antibodies are well known for their role in allergic diseases and for contributions to antiparasitic immune responses. Properties of this antibody... (Review)
Review
Immunoglobulin E (IgE) antibodies are well known for their role in allergic diseases and for contributions to antiparasitic immune responses. Properties of this antibody class that mediate powerful effector functions may be redirected for the treatment of solid tumours. This has led to the rise of a new class of therapeutic antibodies to complement the armamentarium of approved tumour targeting antibodies, which to date are all IgG class. The perceived risk of type I hypersensitivity reactions following administration of IgE has necessitated particular consideration in the development of these therapeutic agents. Here, we bring together the properties of IgE antibodies pivotal to the hypothesis for superior antitumour activity compared to IgG, observations of in vitro and in vivo efficacy and mechanisms of action, and a focus on the safety considerations for this novel class of therapeutic agent. These include in vitro studies of potential hypersensitivity, selection of and observations from appropriate in vivo animal models and possible implications of the high degree of glycosylation of IgE. We also discuss the use of ex vivo predictive and monitoring clinical tools, as well as the risk mitigation steps employed in, and the preliminary outcomes from, the first-in-human clinical trial of a candidate anticancer IgE therapeutic.
PubMed: 33081206
DOI: 10.3390/antib9040055 -
Biomolecules Sep 2022Galectin-10 is a member of the lectin family and one of the most abundant cytoplasmic proteins in human eosinophils. Except for some myeloid leukemia cells, basophils,... (Review)
Review
Galectin-10 is a member of the lectin family and one of the most abundant cytoplasmic proteins in human eosinophils. Except for some myeloid leukemia cells, basophils, and minor T cell populations, galectin-10 is exclusively present in eosinophils in the human body. Galectin-10 forms Charcot-Leyden crystals, which are observed in various eosinophilic diseases. Accumulating studies have indicated that galectin-10 acts as a new biomarker for disease activity, diagnosis, and treatment effectiveness in asthma, eosinophilic esophagitis, rhinitis, sinusitis, atopic dermatitis, and eosinophilic granulomatosis with polyangiitis. The extracellular release of galectin-10 is not mediated through conventional secretory processes (piecemeal degranulation or exocytosis), but rather by extracellular trap cell death (ETosis), which is an active cell death program. Eosinophils undergoing ETosis rapidly disintegrate their plasma membranes to release the majority of galectin-10. Therefore, elevated galectin-10 levels in serum and tissue suggest a high degree of eosinophil ETosis. To date, several studies have shown that galectin-10/Charcot-Leyden crystals are more than just markers for eosinophilic inflammation, but play functional roles in immunity. In this review, we focus on the close relationship between eosinophils and galectin-10, highlighting this protein as a potential new biomarker in eosinophilic diseases.
Topics: Humans; Churg-Strauss Syndrome; Granulomatosis with Polyangiitis; Eosinophils; Biomarkers; Galectins
PubMed: 36291593
DOI: 10.3390/biom12101385 -
Experimental Hematology Jan 2022Inflammatory and immune signals are involved in stressed hematopoiesis under myeloablation, infection, chronic inflammation, and aging. These signals also affect... (Review)
Review
Inflammatory and immune signals are involved in stressed hematopoiesis under myeloablation, infection, chronic inflammation, and aging. These signals also affect malignant pathogenesis, and the dysregulated immune environment which causes the resistance to treatment. On activation, various types of protein tyrosine kinases in the cytoplasm mediate the cascade, leading to the transcription of target genes in the nucleus. Adaptor molecules are commonly defined as proteins that lack enzymatic activity, DNA-binding or receptor functions and possess protein-protein or protein-lipid interaction domains. By binding to specific domains of signaling molecules, adaptor proteins adjust the signaling responses after the ligation of receptors of soluble factors, including cytokines, chemokines, and growth factors, as well as pattern recognition receptors such as toll-like receptors. The signal-transducing adaptor protein (STAP) family regulates various intracellular signaling pathways. These proteins have a pleckstrin homology domain in the N-terminal region and an SRC-homology 2-like domain in the central region, representing typical binding structures as adapter proteins. Following the elucidation of the effects of STAPs on terminally differentiated immune cells, such as macrophages, T cells, mast cells, and basophils, recent findings have indicated the critical roles of STAP-2 in B-cell progenitor cells in marrow under hematopoietic stress and STAP-1 and -2 in BCR-ABL-transduced leukemogenesis. In this review, we focus on the role of STAPs in the bone marrow.
Topics: Adaptor Proteins, Signal Transducing; Animals; Bone Marrow; Hematologic Neoplasms; Hematopoiesis; Humans; Phosphoproteins; Signal Transduction
PubMed: 34780812
DOI: 10.1016/j.exphem.2021.11.002 -
Cells Apr 2022Two-pore channels (TPCs) are ligand-gated cation-selective ion channels that are preserved in plant and animal cells. In the latter, TPCs are located in membranes of... (Review)
Review
Two-pore channels (TPCs) are ligand-gated cation-selective ion channels that are preserved in plant and animal cells. In the latter, TPCs are located in membranes of acidic organelles, such as endosomes, lysosomes, and endolysosomes. Here, we focus on the function of these unique ion channels in mast cells, which are leukocytes that mature from myeloid hematopoietic stem cells. The cytoplasm of these innate immune cells contains a large number of granules that comprise messenger substances, such as histamine and heparin. Mast cells, along with basophil granulocytes, play an essential role in anaphylaxis and allergic reactions by releasing inflammatory mediators. Signaling in mast cells is mainly regulated via the release of Ca from the endoplasmic reticulum as well as from acidic compartments, such as endolysosomes. For the crosstalk of these organelles TPCs seem essential. Allergic reactions and anaphylaxis were previously shown to be associated with the endolysosomal two-pore channel TPC1. The release of histamine, controlled by intracellular Ca signals, was increased upon genetic or pharmacologic TPC1 inhibition. Conversely, stimulation of TPC channel activity by one of its endogenous ligands, namely nicotinic adenine dinucleotide phosphate (NAADP) or phosphatidylinositol 3,5-bisphosphate (PI(3,5)P), were found to trigger the release of Ca from the endolysosomes; thereby improving the effect of TPC1 on regulated mast cell degranulation. In this review we discuss the importance of TPC1 for regulating Ca homeostasis in mast cells and the overall potential of TPC1 as a pharmacological target in anti-inflammatory therapy.
Topics: Anaphylaxis; Animals; Calcium; Calcium Channels; Endosomes; Histamine; Homeostasis; NADP
PubMed: 35563771
DOI: 10.3390/cells11091465 -
Journal of Biomedical Optics Apr 2023Leukocytes are mainly composed of neutrophils, basophils, eosinophils, monocytes, and lymphocytes. The number and proportion of different types of leukocytes correspond...
SIGNIFICANCE
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.
AIM
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.
APPROACH
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.
RESULTS
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.
CONCLUSIONS
The experimental results show that the method achieves good segmentation results for lymphocytes, basophils, neutrophils, eosinophils, and monocytes.
Topics: Leukocytes; Cytoplasm; Image Processing, Computer-Assisted
PubMed: 37065646
DOI: 10.1117/1.JBO.28.4.045002 -
Frontiers in Cell and Developmental... 2023Cerebral amyloid angiopathy (CAA) is a kind of disease in which amyloid β (Aβ) and other amyloid protein deposits in the cerebral cortex and the small blood vessels of... (Review)
Review
Cerebral amyloid angiopathy (CAA) is a kind of disease in which amyloid β (Aβ) and other amyloid protein deposits in the cerebral cortex and the small blood vessels of the brain, causing cerebrovascular and brain parenchymal damage. CAA patients are often accompanied by cardiac injury, involving Aβ, tau and transthyroxine amyloid (ATTR). Aβ is the main injury factor of CAA, which can accelerate the formation of coronary artery atherosclerosis, aortic valve osteogenesis calcification and cardiomyocytes basophilic degeneration. In the early stage of CAA (pre-stroke), the accompanying locus coeruleus (LC) amyloidosis, vasculitis and circulating Aβ will induce first hit to the heart. When the CAA progresses to an advanced stage and causes a cerebral hemorrhage, the hemorrhage leads to autonomic nervous function disturbance, catecholamine surges, and systemic inflammation reaction, which can deal the second hit to the heart. Based on the brain-heart axis, CAA and its associated cardiac injury can create a vicious cycle that accelerates the progression of each other.
PubMed: 36910141
DOI: 10.3389/fcell.2023.1156970 -
Frontiers in Allergy 2022Soon after the release of the new anti-COVID mRNA vaccines, reports came in from the US and the UK of anaphylactic reactions. Fueled by the necessary caution toward... (Review)
Review
Soon after the release of the new anti-COVID mRNA vaccines, reports came in from the US and the UK of anaphylactic reactions. Fueled by the necessary caution toward these new vaccine platforms, these reports had a great impact and were largely commented upon in the scientific literature and global media. The current estimated frequency is of 5 cases per million doses. Very little biological data are presented in the literature to support the anaphylaxis diagnosis in these patients in addition to skin tests. Allergic reactions to vaccines are rare and mostly due to vaccine excipient. Therefore, the poly-ethylene-glycol (PEG) present in both mRNA formulation, and already known to be immunogenic, was soon suspected to be the potential culprit. Several hypersensitivity mechanisms to PEG or to other vaccine components can be suspected, even if the classical IgE-dependent anaphylaxis seems to be one of the most plausible candidates. In the early 2022, the international guidelines recommended to perform skin prick tests and basophil activation tests (BAT) in people experiencing allergic reaction to the first dose of COVID-19 vaccine or with a history of PEG allergy. The aim of this review is to discuss the main potential mechanisms of immediate allergy to COVID19 vaccines based on published data, together with the various techniques used to confirm or not sensitization to one component.
PubMed: 36249342
DOI: 10.3389/falgy.2022.1007602