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Allergy Feb 2023Chronic spontaneous urticaria (CSU) is a debilitating skin disease characterized by intensely itchy wheals, angioedema, or both. Symptoms recur spontaneously, on a... (Review)
Review
Chronic spontaneous urticaria (CSU) is a debilitating skin disease characterized by intensely itchy wheals, angioedema, or both. Symptoms recur spontaneously, on a near-daily basis, over >6 weeks; many patients experience flare-ups over several years and, consequently, reduced quality of life. Differences between the inflammatory profiles of the skin of CSU patients (wheals and nonlesional sites) and healthy controls indicate that key drivers such as mast cells, eosinophils, and basophils interact, release vasoactive mediators, and prime the skin, leaving patients predisposed to symptoms. Many cytokines and chemokines involved in these inflammatory networks and their corresponding intracellular signaling cascades have been identified. These insights informed the development of therapies such as omalizumab, dupilumab, and Bruton's tyrosine kinase (BTK) inhibitors, marking a renewed focus on pathogenesis in CSU clinical research. Despite progress, current therapies provide symptomatic control but do not appear to redress the inflammatory balance in the skin permanently. A deeper understanding of CSU pathogenesis will permit a more targeted approach to developing novel treatments with curative intent. Here, we review what is known about the pathogenesis of CSU and consider how this can be used to identify rational targets to improve patient care further.
Topics: Humans; Anti-Allergic Agents; Quality of Life; Chronic Disease; Urticaria; Omalizumab; Chronic Urticaria
PubMed: 36448493
DOI: 10.1111/all.15603 -
International Journal of Molecular... Feb 2019Interleukin (IL)-18 was originally discovered as a factor that enhanced IFN-γ production from anti-CD3-stimulated Th1 cells, especially in the presence of IL-12. Upon... (Review)
Review
Interleukin (IL)-18 was originally discovered as a factor that enhanced IFN-γ production from anti-CD3-stimulated Th1 cells, especially in the presence of IL-12. Upon stimulation with Ag plus IL-12, naïve T cells develop into IL-18 receptor (IL-18R) expressing Th1 cells, which increase IFN-γ production in response to IL-18 stimulation. Therefore, IL-12 is a commitment factor that induces the development of Th1 cells. In contrast, IL-18 is a proinflammatory cytokine that facilitates type 1 responses. However, IL-18 without IL-12 but with IL-2, stimulates NK cells, CD4⁺ NKT cells, and established Th1 cells, to produce IL-3, IL-9, and IL-13. Furthermore, together with IL-3, IL-18 stimulates mast cells and basophils to produce IL-4, IL-13, and chemical mediators such as histamine. Therefore, IL-18 is a cytokine that stimulates various cell types and has pleiotropic functions. IL-18 is a member of the IL-1 family of cytokines. IL-18 demonstrates a unique function by binding to a specific receptor expressed on various types of cells. In this review article, we will focus on the unique features of IL-18 in health and disease in experimental animals and humans.
Topics: Animals; Disease Susceptibility; Gene Expression Regulation; Humans; Immune System; Interleukin-18; Interleukin-33; Molecular Targeted Therapy; Protein Binding; Receptors, Interleukin-18; Signal Transduction
PubMed: 30717382
DOI: 10.3390/ijms20030649 -
Annual Review of Pathology Jan 2017Chronic rhinosinusitis (CRS) is a troublesome, chronic inflammatory disease that affects over 10% of the adult population, causing decreased quality of life, lost... (Review)
Review
Chronic rhinosinusitis (CRS) is a troublesome, chronic inflammatory disease that affects over 10% of the adult population, causing decreased quality of life, lost productivity, and lost time at work and leading to more than a million surgical interventions annually worldwide. The nose, paranasal sinuses, and associated lymphoid tissues play important roles in homeostasis and immunity, and CRS significantly impairs these normal functions. Pathogenic mechanisms of CRS have recently become the focus of intense investigations worldwide, and significant progress has been made. The two main forms of CRS that have been long recognized, with and without nasal polyps, are each now known to be heterogeneous, based on underlying mechanism, geographical location, and race. Loss of the immune barrier, including increased permeability of mucosal epithelium and reduced production of important antimicrobial substances and responses, is a common feature of many forms of CRS. One form of CRS with polyps found worldwide is driven by the cytokines IL-5 and IL-13 coming from Th2 cells, type 2 innate lymphoid cells, and probably mast cells. Type 2 cytokines activate inflammatory cells that are implicated in the pathogenic mechanism, including mast cells, basophils, and eosinophils. New classes of biological drugs that block the production or action of these cytokines are making important inroads toward new treatment paradigms in polypoid CRS.
Topics: Adult; Chronic Disease; Humans; Nasal Polyps; Rhinitis; Sinusitis
PubMed: 27959637
DOI: 10.1146/annurev-pathol-052016-100401 -
International Journal of Molecular... May 2023Chronic rhinosinusitis with nasal polyps (CRSwNP) has long been considered a benign, chronic inflammatory, and hyperplastic disease. Recent studies have shown that... (Review)
Review
Chronic rhinosinusitis with nasal polyps (CRSwNP) has long been considered a benign, chronic inflammatory, and hyperplastic disease. Recent studies have shown that autoimmune-related mechanisms are involved in the pathology of nasal polyps. Activated plasma cells, eosinophils, basophils, innate type 2 lymphocytes, mast cells, and proinflammatory cytokine in polyp tissue indicate the mobilization of innate and adaptive immune pathways during polyp formation. The discovery of a series of autoantibodies further supports the autoimmune nature of nasal polyps. Local homeostasis dysregulation, infection, and chronic inflammation may trigger autoimmunity through several mechanisms, including autoantigens overproduction, microbial translocation, molecular mimicry, superantigens, activation or inhibition of receptors, bystander activation, dysregulation of Toll-Like Receptors (TLRs), epitope spreading, autoantigens complementarity. In this paper, we elaborated on the microbiome-mediated mechanism, abnormal host immunity, and genetic changes to update the role of autoimmunity in the pathogenesis of chronic rhinosinusitis with nasal polyps.
Topics: Humans; Nasal Polyps; Autoimmunity; Inflammation; Sinusitis; Chronic Disease; Plasma Cells; Autoantigens; Rhinitis
PubMed: 37176151
DOI: 10.3390/ijms24098444 -
Current Pharmaceutical Design 2023Drug hypersensitivity is increasing worldwide as the consumption of drug is increasing. Many clinical presentations of drug hypersensitivity are complex and take place... (Review)
Review
Drug hypersensitivity is increasing worldwide as the consumption of drug is increasing. Many clinical presentations of drug hypersensitivity are complex and take place in the setting of illness and/or polypharmacotherapy. To review the most recent findings in the diagnosis and management of immediate drug hypersensitivity reactions. Studies were selected based on their relevance, originality and date of publication. The understanding of endotypes, biomarkers and phenotypes has improved the categorization of immediate hypersensitivity reactions. In this review, we discussed the short- and long-term management of anaphylaxis with a special focus on in vivo and in vitro diagnostic methods. Moreover, the clinical management of drug-induced anaphylaxis, the role of hidden allergens and the importance of delabeling are discussed. Endophenotyping is crucial to correctly diagnose and treat patients with immediate drug hypersensitivity reactions, preventing future episodes through drug desensitization.
Topics: Humans; Anaphylaxis; Drug Hypersensitivity; Hypersensitivity, Immediate; Biomarkers; Allergens; Skin Tests
PubMed: 36284381
DOI: 10.2174/1381612829666221024154951 -
F1000Research 2017Chronic urticaria is a spontaneous or inducible group of diseases characterized by the occurrence of wheals (and, in about half of cases, angioedema) for more than 6... (Review)
Review
Chronic urticaria is a spontaneous or inducible group of diseases characterized by the occurrence of wheals (and, in about half of cases, angioedema) for more than 6 weeks. These are rather frequent conditions that may severely affect patients' quality of life and sometimes represent a challenge for doctors as well. The causes of chronic urticaria are still poorly defined, although there is growing evidence that different biologic systems including immunity, inflammation, and coagulation may take part in the pathomechanism eventually leading to mast cell and basophil degranulation and hence to wheal formation. This review will discuss the main findings that are (slowly) shedding light on the pathogenesis of this disorder.
PubMed: 28751972
DOI: 10.12688/f1000research.11546.1 -
Survey of Ophthalmology 2023A 23-year-old previously healthy woman presented with headache, generalized seizures, ataxia, encephalopathy, abdominal pain, nausea, and vomiting culminating in a...
A 23-year-old previously healthy woman presented with headache, generalized seizures, ataxia, encephalopathy, abdominal pain, nausea, and vomiting culminating in a 40-pound weight loss. A contrasted magnetic resonance imaging scan of the brain showed T2/FLAIR hyperintensities in the sulci of the occipital and parietal lobes, a punctate focus of restricted diffusion along the inferior aspect of the left caudate head and an empty sella. A lumbar puncture showed an opening pressure of 55 cm H2O, and kidney, ureter, and bladder X ray showed a radiopaque particle in the colon. Serum lead level was 85 mcg/dL (<3.5). Blood smear showed foreign bodies identified as lead particles in the blood with basophilic stippling of RBCs. She was treated with chelation therapy and bowel irrigation and eventually recovered. Further investigation indicated that she was being slowly poisoned by her husband, a chiropractor who had access to lead.
Topics: Female; Humans; Young Adult; Adult; Lead; Magnetic Resonance Imaging; Brain; Brain Diseases
PubMed: 37211095
DOI: 10.1016/j.survophthal.2023.05.005 -
Cytokine Sep 2015Interleukin-4 (IL-4), IL-5 and IL-13, the signature cytokines that are produced during type 2 immune responses, are critical for protective immunity against infections... (Review)
Review
Interleukin-4 (IL-4), IL-5 and IL-13, the signature cytokines that are produced during type 2 immune responses, are critical for protective immunity against infections of extracellular parasites and are responsible for asthma and many other allergic inflammatory diseases. Although many immune cell types within the myeloid lineage compartment including basophils, eosinophils and mast cells are capable of producing at least one of these cytokines, the production of these "type 2 immune response-related" cytokines by lymphoid lineages, CD4 T helper 2 (Th2) cells and type 2 innate lymphoid cells (ILC2s) in particular, are the central events during type 2 immune responses. In this review, I will focus on the signaling pathways and key molecules that determine the differentiation of naïve CD4 T cells into Th2 cells, and how the expression of Th2 cytokines, especially IL-4 and IL-13, is regulated in Th2 cells. The similarities and differences in the differentiation of Th2 cells, IL-4-producing T follicular helper (Tfh) cells and ILC2s as well as their relationships will also be discussed.
Topics: Animals; Asthma; Cell Differentiation; Chromatin; Eosinophils; GATA3 Transcription Factor; Humans; Hypersensitivity; Immunity, Innate; Inflammation; Interleukin-13; Interleukin-4; Lymphocyte Activation; Lymphocytes; Mast Cells; Receptors, Antigen, T-Cell; Receptors, Notch; STAT5 Transcription Factor; Signal Transduction; Th2 Cells
PubMed: 26044597
DOI: 10.1016/j.cyto.2015.05.010 -
Advances in Experimental Medicine and... 2022The recent discovery of new innate lymphoid cells (ILCs) has revolutionized the field of allergies. Since most allergic diseases induce a type 2 immune response, Th2...
The recent discovery of new innate lymphoid cells (ILCs) has revolutionized the field of allergies. Since most allergic diseases induce a type 2 immune response, Th2 cells, which produce IL-4, IL-5, and IL-13 in an antigen-dependent manner, in addition to basophils and mast cells which are activated by antigen-specific IgE, are thought to play a major role in the pathogenesis. However, since group 2 innate lymphoid cells (ILC2s) produce type 2 cytokines (i.e., IL-2, IL-4, IL-5, IL-6, IL-9, IL-13, GM-CSF, and amphiregulin) in response to various cytokines, including IL-33 in the surrounding environment, the possibility has emerged that there are two types of allergies: allergies induced in an antigen-dependent manner by Th2 cells and allergies induced in an antigen-independent manner by ILC2s. In order to make an impact on the increasing incidence of allergic diseases in the world, it is essential to research and develop new treatments that focus not only on Th2 cells but also on ILC2s. In this chapter, the role of ILCs in allergic diseases, which has rapidly changed with the discovery of ILCs, is discussed, focusing mainly on ILC2s.
Topics: Cytokines; Humans; Hypersensitivity; Immunity, Innate; Interleukin-13; Interleukin-4; Interleukin-5; Lymphocytes
PubMed: 35567742
DOI: 10.1007/978-981-16-8387-9_6