Mechanism of Action of Allergen Immunotherapy (original) (raw)
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T-cell responses during allergen-specific immunotherapy
Current Opinion in Allergy & Clinical Immunology, 2012
Purpose of review Allergen-specific immunotherapy is the only specific, dose-dependent and time-dependent and diseasemodifying strategy for the treatment of allergy associated with clinical improvement and biological tolerance which may persist years after discontinuation. Recent findings Successful immunotherapy in respiratory allergy is associated with the immunodeviation of Th2 response to a more protective allergen-specific Th1 cells and with the induction of interleukin-10 (IL-10)/transforming growth factor (TGF)-b-producing T regulatory cells in blood and inflamed airways. Subcutaneous treatment and sublingual treatments induce similar alterations which are dose-dependent and time-dependent. Summary This study provides an update on the immunological T-cell responses during subcutanous immunotherapy and sublingual immunotherapy, giving a unifying view of the redirecting mechanisms and regulating mechanisms elicited by these treatments.
Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy, 2004
Background T helper (Th)2 cells play an important role in the development of IgE-mediated diseases, with local overproduction of Th2 cytokines at the site of allergic inflammation. Furthermore, IL-10 has been suggested to play a modulatory role in the induction and maintenance of allergen-specific tolerance in human atopic diseases. Aim We studied whether circulating allergen-specific Th2 cells persist outside the season of exposure in patients mono-sensitized to birch pollen and whether healthy control individuals also have allergen-specific Th2 cells. We also studied whether IL-10-producing allergen-specific T cells can be found in circulation either in healthy controls or in allergic patients. Methods Blood was drawn outside the birch-pollen season from 15 birch-pollen-allergic patients, with seasonal respiratory symptoms and with (n 5 12) or without (n 5 3) oral allergy syndrome, and from 10 matched healthy controls. Peripheral blood mononuclear cells (PBMCs) were stimulated in vitro with recombinant Bet v 1 allergen, control antigen tetanus toxoid (TT) and anti-CD3/CD80. In part of the cultures, rIL-4 was added in order to reinforce the allergen-specific Th2 cell responses.
Applications and mechanisms of immunotherapy in allergic rhinitis and asthma
Therapeutic Advances in Respiratory Disease, 2016
Clinical and immunologic tolerance are hallmarks of successful allergen immunotherapy (AIT). Clinical benefits such as reduced symptoms, pharmacotherapy intake and improvement of quality of life persist following cessation of treatment. Successful AIT is associated with suppression of allergic inflammatory cells such as mast cells, eosinophils and basophils in target organs. Furthermore, AIT down-regulates type 2 innate lymphoid cells and allergen-specific type 2 T-helper (Th2) cells. The immunologic tolerant state following AIT is associated with the induction of distinct phenotypes of regulatory T-cells (T-regs) including interleukin (IL)-10-, IL-35- and transforming growth factor (TGF)-β- producing T-regs and FoxP3+ T-regs. B-cell responses, including the induction of IL-10+ regulatory B-cells (B-regs) and the production of IgG4-associated blocking antibodies are also induced following successful AIT. These events are associated with the suppression of antigen-specific Th2 respon...
The Journal of Immunology, 2007
Allergen immunotherapy (IT) has long-term efficacy in IgE-mediated allergic rhinitis and asthma. IT has been shown to modify lymphocyte responses to allergen, inducing IL-10 production and IgG Abs. In contrast, a putative role for IgA and local TGF--producing cells remains to be determined. In 44 patients with seasonal rhinitis/asthma, serum IgA1, IgA2, and polymeric (J chain-containing) Abs to the major allergen Phl p 5 were determined by ELISA before and after a 2-year double-blind trial of grass pollen (Phleum pratense) injection IT. Nasal TGF- expression was assessed by in situ hybridization. Sera from five IT patients were fractionated for functional analysis of the effects of IgA and IgG Abs on IL-10 production by blood monocytes and allergen-IgE binding to B cells. Serum Phl p 5-specific IgA2 Abs increased after a 2-year treatment (ϳ8-fold increase, p ؍ 0.002) in contrast to IgA1. Increases in polymeric Abs to Phl p 5 (ϳ2-fold increase, p ؍ 0.02) and in nasal TGF- mRNA (p ؍ 0.05) were also observed, and TGF- mRNA correlated with serum Phl p 5 IgA2 (r ؍ 0.61, p ؍ 0.009). Post-IT IgA fractions triggered IL-10 secretion by monocytes while not inhibiting allergen-IgE binding to B cells as observed with IgG fractions. This study shows for the first time that the IgA response to IT is selective for IgA2, correlates with increased local TGF- expression, and induces monocyte IL-10 expression, suggesting that IgA Abs could thereby contribute to the tolerance developed in IT-treated allergic patients.
T cell responses induced by allergen-specific immunotherapy
Clinical and Experimental Immunology, 2010
Summary Allergen-specific immunotherapy is recognized as a highly effective practice in the treatment of patients with severe allergic rhinitis and/or asthma and is recommended by World Health Organization as an integrated part of allergy management strategy. Several studies have shown that allergen-specific immunotherapy, based on the administration of increasing doses of allergen, achieves a hyposensitization and reduces both early and late responses occurring during the natural exposure to the allergen itself. This is the unique antigen-specific immunomodulatory treatment in current use for human diseases. Successful immunotherapy is associated with reductions in symptoms and medication scores and improved quality of life. After interruption it usually confers long-term remission of symptoms and prevents the onset of new sensitizations in children up to a number of years. Subcutaneous immunotherapy usually suppresses the allergen-induced late response in target organs, likely due...
Allergen immunotherapy: routes, safety,efficacy, and mode of action
ImmunoTargets and Therapy, 2013
Allergic rhinitis, allergic conjunctivitis, and allergic asthma have been steadily increasing in prevalence in recent years. These allergic diseases have a major impact on quality of life and are a major economic burden in the US. Although allergen avoidance and pharmacotherapy are currently the mainstays of therapy, they are not always successful in treating patients' symptoms effectively. If a patient fails allergen avoidance and medical therapy, immunotherapy may be indicated. Furthermore, immunotherapy is the only therapy that may change the course of the disease and induce long-term remission. Though subcutaneous administration has been the standard route for immunotherapy for many decades, there are several other routes of administration that have been and are currently being studied. The goal of utilizing alternative routes of immunotherapy is to improve safety without decreasing the efficacy of treatment. This paper will review the novel routes of immunotherapy, including sublingual, oral, local nasal, epicutaneous, and intralymphatic.
New Routes of Allergen Immunotherapy
American Journal of Rhinology & Allergy, 2016
Objectives Allergen immunotherapy is the only cure for immunoglobulin E mediated type I respiratory allergies. Subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are the most common treatments. In this article, we reviewed new routes of allergen immunotherapy. Methods Data on alternative routes to allow intralymphatic immunotherapy (ILIT), epicutaneous immunotherapy (EPIT), local nasal immunotherapy (LNIT), oral immunotherapy (OIT), and oral mucosal immunotherapy (OMIT) were gathered from the literature and were discussed. Results ILIT features direct injection of allergens into lymph nodes. ILIT may be clinically effective after only a few injections and induces allergen-specific immunoglobulin G, similarly to SCIT. A limitation of ILIT is that intralymphatic injections are required. EPIT features allergen administration by using patches mounted on the skin. EPIT seeks to target epidermal antigen–presenting Langerhans cells rather than mast cells or the vasculatu...
Allergen immunotherapy: 100 years, but it does not look like
European annals of allergy and clinical immunology
Allergen immunotherapy (AIT) is the only treatment able to act on the causes and not merely on the symptoms of allergy. AIT was introduced 100 years ago but remained an empirical treatment for more than 40 years, when the first controlled trial in 1954 opened the era of scientific evidence. A major advance was the introduction of venom immunotherapy to prevent anaphylaxis from insect stings in 1978. Concerning inhalant allergens, currently AIT may be administered in two forms, subcutaneous (SCIT), and sublingual immunotherapy (SLIT). A large number of trials, globally analyzed in a number of meta-analyses, gave sound evidence to the efficacy and safety of SCIT and SLIT in allergic rhinitis and asthma. Adverse systemic reactions are still a drawback for SCIT while safety and tolerability of SLIT are very good, provided recommended doses and schedules of administration are used A significant advance for SLIT development was the registration in Europe of the standardized quality tablet...
Preventive actions of allergen immunotherapy: the facts and the effects in search of evidence
Clinical and molecular allergy : CMA, 2017
Allergen immunotherapy (AIT) is the only treatment that works on the causes of allergy. Available AIT nowadays are subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) for allergic rhinitis and asthma, while for allergy to Hymenoptera venom only subcutaneous route is recommended. A bulk of trials and meta-analyses demonstrated that efficacy and safety of AIT in decreasing allergic clinical symptoms and use of rescue medications, while its preventive capacity is yet under investigation. The most important of these effects is the prevention of potentially fatal anaphylactic reactions to Hymenoptera stings by venom immunotherapy (VIT). A certain number of studies thus far available showed that AIT, in both forms, is able to prevent the progress of allergic rhinitis into asthma and the development of new sensitizations. These effects should be related to the mechanisms of action of AIT. In fact, it has been demonstrated that both SCIT and SLIT are able to modify the all...