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    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.
    Allergology International 12/2013; 62(4):403-13.
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    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.
    The Journal of allergy and clinical immunology 10/2013;
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    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.
    Expert opinion on biological therapy 10/2013;
  • Allergy 07/2013; 68(7):825-8.
  • The Journal of allergy and clinical immunology 06/2013;
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    ABSTRACT: Recombinant allergens for immunotherapy aim to overcome the problems of natural extracts as they can be produced in unlimited amounts with exact physiochemical and immunological properties. These can be modified to have more favourable characteristics including reduced IgE reactivity or enhanced immunogenicity. Different types of recombinant allergens have been evaluated in clinical phase II and III trials whilst others are currently under development. In this review, we identified double-blind, placebo-controlled randomised clinical trials assessing the efficacy and safety of various recombinant allergen preparations. The majority of studies have up to now focused on cat, grass, birch, ragweed and bee venom allergens. Some studies have shown some of these preparations to be effective and well tolerated. However, there are still outstanding issues regarding optimum doses, minimising side effects and long-term effects.
    Current Allergy and Asthma Reports 06/2013;
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    ABSTRACT: BACKGROUND: The pruritic cytokine IL-31 has been shown to be expressed by murine activated effector T Lymphocytes of a TH2 phenotype. Like IL-17 and IL-22, IL-31 is a tissue-signaling cytokine the receptor of which is mainly found on nonimmune cells. An overabundance of IL-31 has been shown in patients with atopic disorders, including dermatitis, as well as asthma, and therefore represents a promising drug target, although its regulation in the context of the human TH2 clusters is not yet known. OBJECTIVE: We sought to address the gene regulation of human IL-31 and to test whether IL-31 possesses a similar proallergic function as members of the human TH2 cytokine family, such as IL-4, IL-5, and IL-13. METHODS: Polyclonal and purified protein derivative of tuburculin-specific T-cell clones were generated. TH phenotype was determined, and IL-31 was measured by means of ELISA. Gene expression of primary bronchial epithelial cells treated with IL-31 was also measured. RESULTS: IL-31 was expressed by all of the TH2 clones and not by TH1, TH17, or TH22. This expression was dependent on autocrine IL-4 expression from these clones because it could be reduced if blocking antibodies to IL-4 were present. Interestingly, TH1 clones were able to express IL-31 if IL-4 was added to culture. This IL-31 expression was transient and did not affect the phenotype of the TH1 clones. IL-31 was able to induce proinflammatory genes, such as CCL2 and granulocyte colony-stimulating factor. CONCLUSION: IL-31 is not a TH2 cytokine in the classical sense but is likely to be expressed by a number of cells in an allergic situation in which IL-4 is present and possibly contribute to the allergic reaction.
    The Journal of allergy and clinical immunology 05/2013;
  • Immunotherapy 03/2013; 5(3):203-6.
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    ABSTRACT: Highlights ► General method to identify the determinants of protective immunity and its application to HTLV-1. ► Observation made that “innate” KIR receptors enhance the HLA class I-restricted response in HTLV-1 infection. ► Description of the mechanisms of HTLV-1 persistence and of the importance of the viral protein HBZ. ► Observation made that CD8+ T cells kill infected, Tax-expressing cells in vivo at a slow rate. ► Description of the role of the HTLV-1 proviral integration site.
    Virology 01/2013; 435(1):131-140.
  • The International Journal of Tuberculosis and Lung Disease 12/2012; 16(12):1565.
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