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    [Show abstract] [Hide abstract] ABSTRACT: Successful allergen-specific immunotherapy (AIT) is associated with a marked decrease in symptoms on allergen exposure, a reduced requirement for 'rescue' anti-allergic drugs and improvement in patients' quality of life. These benefits persist for at least several years following discontinuation of immunotherapy - the hallmark of clinical and immunological tolerance. AIT has been shown to modulate both innate and adaptive immunological responses. Early suppression of innate effector cells of allergic inflammation (mast cells, basophils), regulation of pro-allergic T helper 2 type (Th 2) responses and IgE+ B cell responses have been shown to occur both in the tissue and in the peripheral blood during AIT. The allergen-tolerant state is associated with local and systemic induction of distinct populations of allergen-specific T regulatory cells including IL-10+ Tregs (Tr1 cells), TGF-β+ Tregs and FoxP3+ memory T regs. B cells are switched in favour of producing IgG (particularly IgG4) antibodies and associated blocking activity for IgE-dependent events, including basophil activation and IgE-facilitated allergen binding to B cells. An induction of IL-10+ B regulatory cells and alterations in dendritic cell subsets have also recently been described. These events are followed by the induction of T regulatory cells, suppression of allergen-specific T cell proliferation and immune deviation from Th2 in favour of Th1 responses. Alternative mechanisms of tolerance include apoptosis/deletion of antigen-specific memory Th2 cells and/or a failure of co-stimulation leading to T cell anergy.
    Full-text · Article · Dec 2013 · Allergology International
  • [Show abstract] [Hide abstract] ABSTRACT: According to meta-analyses and reviews, subcutaneous allergen immunotherapy (SCIT) and sublingual allergen immunotherapy (SLIT) are beneficial in patients with allergic rhinitis (AR) and allergic asthma (AA) induced by house dust mites (HDMs). However, the reported effect sizes have varied greatly from one study to another. We sought to perform an evidence-based medicine assessment of commercially available SCIT and SLIT formulations in patients with HDM-induced AA and HDM-induced AR. We searched for double-blind, placebo-controlled randomized clinical trials and analyzed study designs, doses, regimens, patient-reported outcomes, safety reporting, and compliance. Forty-four studies met our inclusion criteria. Some studies tested both SLIT and SCIT or scored both AA and AR outcomes; therefore we reviewed 35 treatment arms in patients with AA (20 for SCIT and 15 for SLIT) and 23 treatment arms in patients with AR (7 for SCIT and 16 for SLIT). The treatment duration ranged from 6 weeks to 3 years. For SCIT, the dose of Der p 1 major allergen (when reported) ranged from 7 to 30 μg for maintenance doses and 60 to 420 μg for cumulative doses. For SLIT, the doses of Der p 1 (when reported) were 0.8 to 70 μg for maintenance doses and 60 to 23,695 μg for cumulative doses. Safety data were often absent or poorly reported. A statistically significant active versus placebo symptom score was observed more frequently for SCIT than for SLIT. There is no consensus on basic treatment parameters (eg, dose and duration) in HDM SCIT and SLIT. There is an urgent need for rigorous, long-term, double-blind, placebo-controlled randomized clinical trials with an efficacy criterion that reflects the particular features of HDM-induced allergic disease.
    No preview · Article · Oct 2013 · The Journal of allergy and clinical immunology
  • [Show abstract] [Hide abstract] ABSTRACT: Introduction: There is an increasing prevalence of atopic diseases such as allergic rhinitis and asthma with house dust mite (HDM) being the common allergen that is highly associated with allergic rhinitis and asthma. Allergen avoidance and pharmacotherapy are part of treatment but it has proved difficult to change the course of HDM-related allergic diseases. Allergen immunotherapy (AIT) has been in use for the past century and has been shown to be effective in the treatment of allergic respiratory disease. Areas covered: This review exclusively focuses on HDM-AIT and discusses the differences in clinical efficacy and safety, long-term effect after discontinuation and immunological changes observed in both HDM-subcutaneous immunotherapy (SCIT) and HDM-sublingual immunotherapy (SLIT) in the treatment of allergic rhinitis and asthma in both pediatric and adult populations. Expert opinion: The majority of studies involved small numbers of patients, variable doses of major allergens and are of variable quality. There is good evidence for HDM-SCIT efficacy and its long-term effect in adults and children, whereas at the present time, evidence for HDM-SLIT is unconvincing, particularly in children. In carefully selected patients, HDM-SCIT is effective and safe. More definitive trials are needed before HDM-SLIT can be recommended in routine practice for rhinitis and/or asthma.
    No preview · Article · Oct 2013 · Expert opinion on biological therapy
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