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anti-FcepsilonRI autoantibodies

C L Goh, K T Tan
It is well-recognized that 30-40% of chronic idiopathic urticaria is autoimmune in nature. Chronic autoimmune urticaria is caused by anti-FcepsilonRI and less frequently, by anti-IgE autoantibodies that lead to mast cell and basophil activation, thereby giving rise to the release of histamine and other proinflammatory mediators. Activation of the classical complement pathway and formation of C5a are important in dermal mast cell activation. C5a is also a neutrophil and eosinophil chemoattractant. Chronic autoimmune urticaria has been found to be associated with autoimmune thyroid disease...
July 2009: Indian Journal of Dermatology
R S Sun, X H Chen, J F Sui, R Q Liu, T M Cheng, X Z Ran, T Yang
Autoimmune diseases have been implicated in the development of intrinsic asthma, however little data are available on the role of autoimmunity in the pathogenesis of asthma. The purpose of this study was to investigate circulating autoantibodies against the high-affinity receptor for immunoglobulin E, FcepsilonRI, in patients with asthma. Seventy-eight patients with asthma and 32 healthy control subjects were included. All individuals were tested using a triple-staining flow cytometry-based basophil activation test (BAT) for the potential presence of autoantibodies against FcepsilonRI...
November 2008: Journal of International Medical Research
Daniel P Potaczek, Chiharu Nishiyama, Marek Sanak, Andrew Szczeklik, Ko Okumura
Our knowledge on the variability of FCER1A gene encoding for alpha-subunit of the high-affinity immunoglobulin E receptor (FcepsilonRI) that plays a central role in the pathogenesis of allergy and related disorders, has been recently much extended. Last findings from FCER1A mutational screening and genetic association studies, followed by functional analyses of the polymorphisms, are briefly summarized in this mini-review. The association between FCER1A gene variants and total serum IgE levels seems especially interesting and, supported by functional analyses of polymorphisms, may provide a rationale for pharmacogenetic studies on anti-IgE therapy that indirectly suppresses FcepsilonRI expression...
2009: Immunologic Research
Riccardo Asero, Piersandro Riboldi, Alberto Tedeschi, Massimo Cugno, Pierluigi Meroni
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...
November 2007: Autoimmunity Reviews
Becky M Vonakis, Kavitha Vasagar, Scott P Gibbons, Laura Gober, Patricia M Sterba, Hyeyoun Chang, Sarbjit S Saini
BACKGROUND: Basophils are implicated in the pathogenesis of chronic idiopathic urticaria (CIU). Autoantibodies to the IgE receptor (FcepsilonRI) and serum histamine releasing activity have been detected in some subjects with CIU, although their role in vivo is unclear. Basophils of patients with CIU have altered FcepsilonRI-mediated histamine release (HR); however, the mechanism is unknown. In the basophil FcepsilonRI signaling pathway, protein levels of Src-homology 2-containing-5'-inositol phosphatase (SHIP)-1 are inversely correlated with the release of mediators or releasability...
February 2007: Journal of Allergy and Clinical Immunology
George Du Toit, Ruth Prescott, Patricia Lawrence, Asmah Johar, Geraldine Brown, Eugene G Weinberg, Cassim Motala, Paul C Potter
BACKGROUND: Chronic urticaria (CU) in childhood remains a challenge for investigation, and its etiology is largely unknown. Autoantibodies to the high-affinity IgE receptor (FcepsilonRI) are believed to play a role in the pathogenesis of this disease in adults. OBJECTIVE: To determine the prevalence of autoantibodies to FcepsilonRIalpha on basophils in children with CU vs atopic eczema dermatitis syndrome (AEDS). METHODS: Eighty children with CU were compared with 38 children with AEDS...
February 2006: Annals of Allergy, Asthma & Immunology
Stephen C Dreskin, Karen Y Andrews
PURPOSE OF REVIEW: Although it is generally accepted that thyroid autoimmunity is more prevalent in patients with chronic urticaria than in the general population, the importance of this finding is unclear. In addition, there are reports that chronic urticaria remits in some but not all patients who have evidence of thyroid autoimmunity and are treated with l-thyroxine. This review will summarize the history of this controversy and suggest a possible role for thyroid autoimmunity in the pathophysiology of chronic urticaria...
October 2005: Current Opinion in Allergy and Clinical Immunology
A Tedeschi, A L Comi, M Lorini, C Tosini, A Miadonna
BACKGROUND: Inflammatory alterations of respiratory airways have been found in patients with non-allergic asthma, but the triggering event has not been defined. An autoimmune activation of inflammatory cells has been hypothesized. OBJECTIVE: To evaluate whether histamine-releasing factors are present in sera from non-allergic asthmatics. METHODS: Twenty-four patients with non-allergic asthma underwent in vivo autologous serum skin test (ASST) and in vitro basophil histamine release assay using autologous basophils as well as basophils from normal donors...
July 2005: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
A Fusari, C Colangelo, F Bonifazi, L Antonicelli
BACKGROUND: The presence of anti-FcepsilonRI and anti-IgE autoantibodies in a subset of patients with chronic urticaria suggests their aetiopathogenetic role. In clinical practice, the presence of these antibodies is usually considered when the autologous serum skin test (ASST) is positive. AIMS: To evaluate if the positive ASST follows up the activity of chronic urticaria. METHODS: Autologous serum skin test and thyroid autoantibody detection were performed in 82 patients with chronic urticaria and repeated 1 year later, when the vast majority of patients were symptom-free...
February 2005: Allergy
Gianni Marone, Maria Bova, Aikaterini Detoraki, Anna Maria Onorati, Francesca W Rossi, Giuseppe Spadaro
Human mast cells, by elaborating vasoactive mediators and cytokines, are the primary effector cells of anaphylaxis. A body of evidence implicates human heart mast cells (HHMCs) in anaphylaxis. These cells have been identified perivascularly, in dose proximity to myocytes and in the arterial intima in human heart tissue. The membrane surface of mast cells from human heart tissue of patients undergoing cardiac transplantation expresses the high affinity receptors for IgE (FcepsilonRI) and C5a receptors. Activation of HHMCs in vitro with anti-IgE or anti-FcepsilonRI induced the release of preformed mediators (histamine, tryptase and chymase) and the de novo synthesis of LTC4 (approximately equal to 18 ng/10(6) cells) and PGD2 (approximately equal to 18 ng/10(6) cells)...
2004: Novartis Foundation Symposium
Ruth A Sabroe, Edda Fiebiger, David M Francis, Dieter Maurer, Paul T Seed, Clive E h Grattan, Anne Kobza Black, Georg Stingl, Malcolm W Greaves, Robert M Barr
BACKGROUND: Circulating autoantibodies against FcepsilonRI, IgE, or both occur in approximately one third of patients with chronic idiopathic urticaria (CIU), but not all autoantibodies initiate histamine release. OBJECTIVE: We sought to classify patients with CIU into subsets on the basis of serum bioactivity and immunoreactivity and to examine the relationship between newly defined subtype and disease severity. METHODS: Sera from patients with CIU (n = 78), dermog-raphism (n = 15), and cholinergic urticaria (n = 10) and sera from healthy subjects (n = 39) were analyzed by means of Western blot analysis for anti-FcepsilonRI autoantibodies and for histamine release from basophils and dermal mast cells...
September 2002: Journal of Allergy and Clinical Immunology
Y Kikuchi, A P Kaplan
BACKGROUND: Approximately 35% to 40% of patients with chronic urticaria possess a circulating antibody directed to the alpha subunit of the high-affinity type I IgE receptor (FcepsilonRI), which is detectable by using histamine release assays or immunoblotting. Prior reports suggest that purified IgG may not directly activate basophils but rather does so through complement activation. OBJECTIVE: We sought to further elucidate the mechanism by which this antibody causes basophil histamine release, including the role of complement, and to reassess the relationship of functional versus binding assays...
June 2001: Journal of Allergy and Clinical Immunology
B M Stadler, S Miescher, M Horn, J Pachlopnik, M Stadler, F Kricek, M Vogel
By means of repertoire cloning we have isolated human anti-IgE antibodies as well as human anti-FcepsilonRI antibodies. Whether the naturally occurring anti-IgE autoantibodies play a pathophysiological role may be disputed, but the beneficial role of recombinant anti-IgE antibodies as a therapeutic agent has been shown. On the other hand, the natural antibodies isolated from an antibody library of a nonallergic individual against the FcepsilonRI alpha-chain are anaphylactogenic, if FcepsilonRI was not occupied...
January 2001: International Archives of Allergy and Immunology
T Takai, T Yuuki, N Iwamoto-Yasue, K Okumura, C Ra
The structural analysis of monoclonal antibodies (mAbs) against the alpha subunit of the high affinity IgE receptor (FcepsilonRIalpha) is an alternative approach to obtaining information for the design of inhibitors that will block complementary interaction between IgE and FcepsilonRIalpha and to analyzing the various biological effects induced by anti-FcepsilonRIalpha autoantibodies in chronic urticaria. In this study, epitopes for mouse anti-human FcepsilonRIalpha mAbs and primary structures of variable regions of the mAbs were analyzed...
September 2000: Bioscience, Biotechnology, and Biochemistry
U Fagiolo, F Kricek, C Ruf, A Peserico, A Amadori, M Cancian
BACKGROUND: Intradermal injection of autologous serum elicits a wheal-and-flare response in about 60% of patients with chronic idiopathic urticaria (CIU). This reactivity has been attributed to the presence of IgG autoantibodies directed against IgE or the alpha-chain of the high-affinity IgE receptor (FcepsilonRIalpha) expressed on basophils and mast cells, leading to the hypothesis that at least some forms of CIU could be sustained by an autoimmune process. OBJECTIVES: The aim of this study was to investigate the relationship between the presence of anti-IgE or anti-FcepsilonRI antibodies and the ability to induce wheal-and-flare responses in CIU sera selected for the capacity to give a positive skin test response...
September 2000: Journal of Allergy and Clinical Immunology
W R Sperr, S Natter, M Baghestanian, J Smolen, K Wolff, B R Binder, M R Müller, K Lechner, R Valenta, P Valent
Schnitzler's syndrome is a rare disease characterized by chronic urticaria, monoclonal IgM, and clinical and laboratory signs of inflammation. In a subset of patients, the urticarial lesions cause pruritus. However, the pathophysiology of the disease and the biochemical basis of urticaria are not known. We describe a female patient with Schnitzler's syndrome suffering from chronic urticaria associated with pruritus. The patient's serum was found to contain IgG antibodies recognizing cellular components of the microvasculature...
August 2000: International Archives of Allergy and Immunology
R A Sabroe, P T Seed, D M Francis, R M Barr, A K Black, M W Greaves
BACKGROUND: Previous studies defining the clinical features of patients with chronic idiopathic urticaria (CIU) were performed before the identification of functional autoantibodies against FcepsilonRI and/or IgE, now known to be present in approximately 30% of patients with CIU. OBJECTIVE: Our purpose was to determine whether there are differences between patients with and those without autoantibodies in the clinical features or severity of CIU. METHODS: The clinical features of 107 patients with CIU were evaluated prospectively...
March 1999: Journal of the American Academy of Dermatology
R A Sabroe, E Poon, G E Orchard, D Lane, D M Francis, R M Barr, M M Black, A K Black, M W Greaves
BACKGROUND: Previous studies defining the histopathologic features of patients with chronic idiopathic urticaria (CIU) were performed on wheals of uncertain duration and before the identification of functional autoantibodies against FcepsilonRI and/or IgE, now known to be present in approximately 30% of patients with CIU. OBJECTIVE: We sought to determine the timing of the inflammatory infiltrate in the wheals of patients with CIU and to detect differences between patients with and without autoantibodies...
March 1999: Journal of Allergy and Clinical Immunology
G Marone, G Spadaro, C Palumbo, G Condorelli
Basophil granulocytes and tissue mast cells and their mediators play a role in the pathogenesis of several immune and inflammatory disorders. Human basophils and mast cells (FcepsilonRI+ cells) can be activated through immunological interaction with the IgE-FcepsilonRI network. FcepsilonRI+ cells can be triggered by cross-linking between the Fab portions of IgE and multivalent antigens (direct anaphylaxis). 'Reverse type' anaphylaxis can occur through three distinct mechanisms: antibodies against the Fcepsilon portion of IgE (anti-IgE), antibodies against epitopes of the alpha chain of FcepsilonRI (anti-FcepsilonRIalpha) and anti-IgG acting on IgG-IgE complexes bound to FcepsilonRI...
January 1999: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
M W Greaves, B F O'Donnell
The aetiology of chronic urticaria in the majority of patients is elusive. The cause of physical urticarias (dermographism, delayed pressure urticaria, cold urticaria) is unknown. We have identified a subset of chronic "idiopathic" urticaria patients, representing approximately 30% of the total in which the disease is caused by the presence of IgG autoantibodies against the high affinity IgE receptor (FcepsilonRIalpha). This functional autoantibody stimulates normal (albeit vicarious) activation of mast cells and basophils via FcepsilonRI, causing whealing and angioedema...
February 1998: Experimental Dermatology
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