Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic urticaria (CU), defined as recurrence of wheals with or without angioedema for more than 6 weeks, is a quite common disease that may severely worsen the quality of life. Studies carried out during the last 2 decades have demonstrated an autoimmune pathogenesis mediated by functionally active autoantibodies to the high affinity IgE receptor (FcepsilonRI) or to IgE which are able to induce histamine release from basophils and mast cells. However, such mechanism can be detected in less than 50% of patients only. The present article reviews recent findings showing an additional pathogenic mechanisms in CU patients: activation of the coagulation cascade resulting in thrombin production. Thrombin is a serine protease which may play a key role in urticaria, being able to induce edema through an increase in vascular permeability, mast cell activation and degranulation, and to induce the production of the anaphylotoxin C5a. Such mechanism seems to be active in the majority of CU patients, however their relationship with anti-FcepsilonRI or anti-IgE autoantibodies is still matter of research.
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PMID:Chronic urticaria: a disease at a crossroad between autoimmunity and coagulation. 1796 29

The increasing amounts of evidence prove that sex hormones modulate different cells function, including mast cells and lymphocytes. Dehydroepiandrosterone (DHEA) and its sulphate ester (DHEA-S) are both the secretory products of adrenal glands and the most abundant hormones in the systemic circulation of humans, converted then into androgens and estrogens in the periphery. DHEA may affect production of Th1 and Th2- associated cytokines, suggesting their significance in diseases where imbalanced lymphocyte activity plays the essential role, also in atopic diseases. Reduced circulating concentration of these androgens has been demonstrated in patients with immune-inflammatory diseases, including atopic eczema/dermatitis syndrome and asthma. It is unknown however, whether such changes contribute in any way to etiopathogenesis of the disorders, or are merely their consequences. Chronic urticaria, not included in the atopic triad, is a mast cell-dependent disease characterised by activation of autoimmune and inflammatory processes responding to different factors. Alterations in the immune-neuro-endocrine milieu may contribute to the development of the disease. It has been demonstrated that DHEA-S concentration is significantly lower in the peripheral circulation of patients suffering from chronic urticaria, as compared with healthy subjects. On one hand, this reflects some changes in hormonal homeostasis in the course of urticarial processes, yet on the other, suggests some possible role for this hormone in pathophysiology of the disease. In this brief review we present the available data on DHEA-S involvement in events associated with atopic allergy as well as chronic urticaria.
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PMID:Dehydroepiandrosterone and dehydroepiandrosterone sulphate in atopic allergy and chronic urticaria. 1828 94

Urticaria is a common pruritic skin disorder that is often seen in the office and varies in severity and chronicity. The etiologic cause is frequently not identifiable. Urticaria may be associated with physical factors and triggers, including foods or medications. A significant percentage of patients with chronic urticaria have circulating autoantibodies directed toward immunoglobulin-E or the high-affinity receptor for immunoglobulin-E (FcepsilonRI), or have antithyroid antibodies that might play a role in the activation of the final common pathway in urticaria: mast cell activation and degranulation. Management begins with a careful investigation and elimination of eliciting factors when identified, followed by treatment of underlying disease. Antihistamines are the current mainstay of pharmacotherapy for urticaria, which provide symptomatic relief in most cases. In severe cases, corticosteroids, hydroxychloroquine sulfate (Plaquenil; Sanofi-Synthelabo, New York, NY), and immunosuppressive agents, including cyclosporin, are sometimes used by specialists.
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PMID:Office-based management of urticaria. 1845 30

Chronic urticaria is characterized by mast cells/basophils activation which initiate the inflammatory response. Pathogenetically, the disease may in many cases represent an autoimmune phenomenon. Altered function of the neuro-endocrine-immune system due to stress and other factors has also been implicated its pathogenesis. Sex hormones modulate immune and inflammatory cell functions, including mast cell secretion, and are regarded as responsible for gender and menstrual cycle phase-associated differential susceptibility and severity of some autoimmune and inflammatory diseases. Chronic urticaria is approximately twice more frequent in women than in men. In addition, urticaria may be associated with some diseases and conditions characterized by hormonal changes, including endocrinopathy, menstrual cycle, pregnancy, menopause and hormonal contraceptives or hormone replacement therapy. Hypersensitivity reactions to endogenous or exogenous female sex hormones have been implicated in the pathogenesis of urticarial lesions associated with estrogen and autoimmune progesterone dermatitis. We observed lower serum dehydroepiandrosterone sulfate (DHEA-S) concentration in patients with chronic urticaria with positive and negative response to autologous serum skin test. Thus, the influence of fluctuations in the hormonal milieu and altered sex hormone expression on the triggering-off, maintenance or aggravation of urticaria should be taken into account. In addition, the possible impact of estrogen mimetics, in the environment and in food, on the development of disease associated with mast cell activation must be considered. This review endeavours to outline what is known about the possible influence of sex hormones in the expression of urticaria.
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PMID:Sex hormones and urticaria. 1848 75

Chronic urticaria is a common skin disease without a clear etiology in the vast majority of cases. The similarity of symptoms and lesion pathology to allergen-induced skin reactions supports the idea that skin mast cell and blood basophil IgE receptor activation is involved; however, no exogenous allergen trigger has been identified. The presence of serum IgG autoantibodies targeting IgE or the IgE receptor in approximately 40% of CIU cases supports the theory of an autoimmune basis for the disease. However, issues remain with the assays to detect autoantibodies among other serum factors, the relationship of autoantibodies to CIU disease activity, and the occurrence of autoantibodies in healthy subjects. Other studies have identified altered IgE receptor degranulation that reverts in disease remission and is accompanied by changes in signaling molecule expression and function in mast cells and basophils in active CIU subjects. The arrival of therapies targeting IgE and the IgE receptor pathway elements has potential use in CIU.
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PMID:New concepts in chronic urticaria. 1883 31

Urticaria is often classified as acute, chronic, or physical based on duration of symptoms and the presence or absence of inducing stimuli. Urticarial vasculitis, contact urticaria, and special syndromes are also included under the broad heading of urticaria. Recent advances in our understanding of the pathogenesis of chronic urticaria include the finding of autoantibodies to mast cell receptors in nearly half of patients with chronic idiopathic urticaria. These patients may have more severe disease and require more aggressive therapies. Extensive laboratory evaluation for patients with chronic urticaria is typically unrevealing and there are no compelling data that associate urticaria with chronic infections or malignancy. Pharmacologic therapy consists primarily of the appropriate use of first- and second-generation histamine H(1) receptor antihistamines. Additional therapy may include leukotriene receptor antagonists, corticosteroids, and immunomodulatory agents for severe, unremitting disease. Despite our greater understanding of the pathogenesis of urticaria, the condition remains a frustrating entity for many patients, particularly those with chronic urticaria.
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PMID:Urticaria : a review. 1917 Apr 6

Urticaria is a common dermatologic condition seen by primary care physicians. Urticaria can result in significant morbidity and a dramatic decline in quality of life. Acute urticaria is mostly an allergic or IgE-mediated reaction and tends to be self-limited, while chronic urticaria generally does not exhibit any specific external cause and is therefore considered idiopathic. Evidence suggests that up to 30% to 50% of idiopathic cases may be autoimmune and/or related to mast cell/basophil abnormalities. There is further evidence of an autoantibody to the high-affinity receptor for IgE (FcepsilonRI), specifically binding to the alpha-chain (FcepsilonRIalpha), which may be pathogenic. The treatment regimen for urticaria needs to be individualized as the severity and clinical pattern can vary considerably between patients. Histamine antagonists are the mainstays of therapy. For more severe or persistent cases, there are few Food and Drug Administration (FDA)-approved options, and there are limited data from controlled trials. Further research is required to develop safe and more effective agents for this disease.
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PMID:An update on acute and chronic urticaria for the primary care provider. 1917 23

Chronic urticaria is a common heterogeneous condition that can be quite debilitating. There are a number of potential causes of urticaria, and the severity and clinical pattern can vary considerably from patient to patient. Eighty to 90% of patients with chronic urticaria have no specific external cause for their disease, which is therefore labeled "chronic idiopathic urticaria." We now know, however, that up to 30-50% of idiopathic cases may be autoimmune or related to mast cell and basophil abnormalities. There is evidence of an autoantibody to the high-affinity receptor for IgE (FcepsilonRI), specifically binding to the alpha-chain (FcepsilonRIalpha), which may be pathogenic. At this point in time, the gold standard for detecting clinically relevant autoantibodies to FcepislonRI is the functional in-vitro donor basophil histamine release assay. The exact prevalence and role of these autoantibodies is still under investigation. Histamine antagonists are the mainstays of therapy. For patients whose symptoms are not controlled by antihistamines alone, there are a number of adjunct therapy options, but there is still a need to develop better agents for this disease.
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PMID:The spectrum of chronic urticaria. 1933 14

Chronic urticaria is defined as the presence of urticaria (hives) for at least 6 weeks with the assumption that it occurs daily or close to it. If we eliminate physical urticarias and urticarial vasculitis from consideration, the remainder can be divided into autoimmune chronic urticaria (45%) and idiopathic chronic urticaria (55%). The autoimmune subgroup is associated with the IgG anti-IgE receptor alpha subunit in 35-40% of patients and IgG anti-IgE in an additional 5-10%. These autoantibodies have been shown to activate blood basophils and cutaneous mast cells in vitro with augmentation of basophil activation by complement and release of C5a, in particular. Binding methods (immunoblot and ELISA) yield positives in many autoimmune diseases as well as occasional normal subjects or patients with other forms of urticaria but most such sera are non-functional. Activation of basophils or mast cells causing histamine release is quite specific for chronic urticaria and defines the autoimmune subgroup. Although pathogenicity is not formally proven, the antibodies cause wealing upon intradermal injection, and removal of the autoantibody leads to remission. A cellular infiltrate is seen to be characterized by mast cell degranulation and infiltration of CD4+ T lymphocytes, monocytes, neutrophils, eosinophils, and basophils. The intensity of the infiltrate and clinical severity of the disease (including accompanying angio-oedema) is more severe in the autoimmune subpopulation. This latter group also has a higher evidence of human leucocyte antigen DR alleles associated with autoimmunity and a 25% incidence of antithyroid antibodies with diagnosed hypothyroidism in some. Hypo-responsiveness of patients' basophils to anti-IgE and hyperresponsiveness to serum defines another subpopulation (at least 50%) that overlaps the idiopathic and autoimmune subgroups. Hypo-responsiveness to anti-IgE has been shown to be associated with elevated levels of cytoplasmic phosphatases that inhibit degranulation. Reversal of the abnormality is seen with disease remission. Further work will be needed to distinguish whether this is a cause or a consequence of persistent urticaria and to further assess the relationship (or lack thereof) of altered responsiveness (decreased or increased) with the presence or absence of activating autoantibodies.
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PMID:Pathogenesis of chronic urticaria. 1940 Sep 5

Chronic urticaria is a common skin disease without an etiology in the majority of cases. The similarity of symptoms and pathology to allergen-induced skin reactions supports the idea that skin mast cell and blood basophil IgE receptor activation is involved; however, no exogenous allergen trigger has been identified. Recent evidence supports a role for blood basophils in disease expression. Specifically, blood basopenia is noted in active disease with the recruitment of blood basophils to skin lesional sites. In addition, blood basophils display altered IgE receptor-mediated degranulation that reverts in disease remission. In active chronic idiopathic urticaria (CIU) subjects, changes in IgE receptor-signaling molecule expression levels accompany the altered degranulation function in blood basophils. The arrival of therapies targeting IgE has further shown that altered blood basophil degranulation behavior has potential use as a disease biomarker in CIU.
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PMID:Basophil responsiveness in chronic urticaria. 1965 75


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