Anti-immunoglobulin E monoclonal antibody administered with immunotherapy
Division of Allergy and Immunology, Department of Internal Medicine, Creighton University, Omaha, Nebraska 68131, USA. Allergy and Asthma Proceedings
(Impact Factor: 3.06).
03/2006; 27(2 Suppl 1):S33-6.
Despite both efficacy and immunotolerogenic effects, many clinicians still are reluctant to use allergen-specific immunotherapy (SIT) because of the potential for acute allergic reactions. The anti-immunoglobulin E monoclonal antibody, omalizumab, is approved by the U.S. Food and Drug Administration for the treatment of moderate-to-severe allergic asthma and has proven to be a relatively safe agent. Knowledge of the distinct immunologic changes elicited by allergen SIT and omalizumab has established a rationale for investigation into their combined use for the management of allergic diseases. This review summarizes two investigative studies examining the safety and efficacy of the combination of omalizumab + allergen SIT for the treatment of allergic rhinitis. Both studies show that the combination of omalizumab and allergen SIT confer added efficacy to either treatment alone. Pretreatment of patients with omalizumab before rush allergen immunotherapy also showed added safety to rush immunotherapy with the prevention of acute allergic reactions. Results thus far provide the opportunity to develop strategies using omalizumab pretreatment to enhance the safety and efficacy of allergen-immunotherapy to treat a wide variety of allergic diseases.
Available from: Basel al-Ramadi
- "Based on evidence obtained in both human and animal studies, a link between Pb exposure, Th2 cytokines, increased IgE production, and allergic diseases has been established (Lutz et al., 1999; Snyder et al., 2000; Annesi-Maesano et al., 2003; Heo et al., 2004; Maezawa et al., 2004; Ban and Hettich, 2005; Holgate et al., 2005; Parks and Casale, 2006). In fact, Pbinduced increase in IgE production has become one of the predominant biomarkers of Pb immunotoxicity (Karmaus et al., 2005; Dietert and Piepenbrink, 2006). "
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ABSTRACT: Persistent exposure to inorganic lead (Pb) is known to adversely affect the immune system. In the present study, we assessed the effect of chronic Pb exposure on susceptibility to infection by the facultative intracellular pathogen Salmonella enterica serovar Typhimurium. Mice were exposed to 10 mM Pb-acetate in drinking water for approximately 16 weeks, resulting in a significant level of Pb in the blood (106.2+/-8.9 microg/dl). Pb exposure rendered mice susceptible to Salmonella infection, manifested by increased bacterial burden in target organs and heightened mortality. Flow cytometric analysis of the splenic cellular composition in normal and Pb-exposed mice revealed no gross alteration in the ratios of B and T lymphocytes or myeloid cells. Similarly, the capacity of B and T cells to upregulate the expression of activation antigens in response to mitogenic or inflammatory stimuli was not hindered by Pb exposure. Analysis of the ability of ex vivo-cultured splenocytes to secrete cytokines demonstrated a marked reduction in IFN-gamma and IL-12p40 production associated with Pb exposure. In contrast, secretion of IL-4 by splenocytes of Pb-treated mice was 3- to 3.6-fold higher than in normal mice. The increased capacity to produce IL-4 correlated with a shift in the in vivo anti-Salmonella antibody response from the protective IgG2a isotype to the Th2-induced IgG1 isotype. We conclude that chronic exposure to high levels of Pb results in a state of immunodeficiency which is not due to an overt cytotoxic or immunosuppressive mechanism, but rather is largely caused by a shift in immune responsiveness to Th2-type reactions.
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ABSTRACT: As clinical experience with omalizumab increases, questions arise from clinicians that are not answered in the product insert or clinical reports. How does this drug really work? There surely must be more than the simple reduction of free IgE which, in and of itself, causes no disease. Can omalizumab be used in patients whose IgE level is below 30 or above 700 IU/mL? Can you treat a pregnant asthmatic woman with omalizumab? What are the updated risks for cancer? Is there a risk for omalizumab-treated patients who travel to parasite-endemic areas? What are the implications of skin-prick tests that remain positive after treatment? Does this drug prevent anaphylaxis with enough assurity to use it in conjunction with immunotherapy (IT) or rush IT? Are the complexes formed as a result of therapy problematic, therapeutic, or inconsequential? How long should this drug be used? It is the purpose of this review to examine these clinical issues and present common strategies for approaching each.
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ABSTRACT: The pharmacological purposes of the anti-IgE therapy are to neutralize IgE and to inhibit its production to attenuate type I hypersensitivity reactions. The therapy is based on humanized IgG1 antibodies that bind to free IgE and to membrane-bound IgE on B cells, but not to IgE bound by the high-affinity IgE.Fc receptors on basophils and mast cells or by the low-affinity IgE.Fc receptors on B cells. After nearly 20 years since inception, therapeutic anti-IgE antibodies (anti-IgE) have been studied in about 30 Phase II and III clinical trials in many allergy indications, and a lead antibody, omalizumab, has been approved for treating patients (12 years and older) with moderate-to-severe allergic asthma. Anti-IgE has confirmed the roles of IgE in the pathogenesis of asthma and helped define the concept "allergic asthma" in clinical practice. It has been shown to be safe and efficacious in treating pediatric allergic asthma and treating allergic rhinitis and is being investigated for treating peanut allergy, atopic dermatitis, latex allergy, and others. It has potential for use to combine with specific and rush immunotherapy for increased safety and efficacy. Anti-IgE thus appears to provide a prophylactic and therapeutic option for moderate to severe cases of many allergic diseases and conditions in which IgE plays a significant role. This chapter reviews the evolution of the anti-IgE concept and the clinical studies of anti-IgE on various disease indications, and presents a comprehensive analysis on the multiple intricate immunoregulatory pharmacological effects of anti-IgE. Finally, it reviews other approaches that target IgE or IgE-expressing B cells.
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