Asthma
James M. Rippe in Lifestyle Medicine, 2019
Allergen immunotherapy can be helpful in certain allergic asthmatic patients.2,27,28 According to the NAEPP Expert Panel Report 3, subcutaneous immunotherapy can be considered for patients who have prominent allergies, as with allergic rhinoconjunctivitis, and who have mild to moderate persistent asthma (steps 2 to 4).2,13 However, it is preferable to have clear evidence of a relationship between asthma symptoms and exposure to the allergen in question. Finally, symptoms should be nearly perennial and difficult to control with pharmacotherapy alone. The whole concept of allergen immunotherapy is under constant debate, in terms of long-term benefit. If allergen immunotherapy is s tarted, it should be given under the careful guidance of a well-trained immunotherapist who is capable of treating any life-threatening reaction that may occur.29 The immunotherapy should be directed at a single or only a very few antigens. There is a paucity of data support for use of multiple-allergen mixes. The responses to therapy may be specific to the allergen extracts and regimens used and it has been recommended to use those allergen extracts shown to have efficacy in clinical trials.13 Finally, the optimal duration of allergen therapy is not clear but typically is three to five years, and a recognizable favorable improvement in asthma should occur early in treatment.
Immunologically Mediated Diseases and Allergic Reactions
Julius P. Kreier in Infection, Resistance, and Immunity, 2022
Allergies to certain foods, dust, or animal dander can be controlled by avoidance of the allergen. However, ubiquitous allergens such as ragweed, grasses, or certain tree pollens are difficult to avoid. Many allergy patients undergo allergen immunotherapy, which is a technique that involves subcutaneous injection of increasing doses of an allergen over a period of weeks or months in hopes of reducing allergen-specific IgE levels. Allergen immunotherapy has proven successful for treatment of allergic asthma and rhinitis, but the mechanism by which this treatment improves clinical symptoms is not entirely clear. Following repeated injections of allergen, there is an increase in antigen-specific IgG antibodies, which are postulated to function by neutralizing antigen, by blocking the interaction of antigen and IgE, and by negatively regulating IgE production through antibody feedback mechanisms. Desensi tiza ti on through continued allergen injection could also downregulate IgE production by shifting the predominance of antigen-specific TH2 T lymphocytes to TH1 cells or by inducing specific T cell tolerance.
Historical perspectives of allergen immunotherapy
Richard F. Lockey, Dennis K. Ledford in Allergens and Allergen Immunotherapy, 2020
Allergen immunotherapy was thought to be clinically effective for many years before a thorough understanding of the mechanisms that underlie its efficacy was achieved. One of the earliest insights into the possibility of allergen desensitization was the proposal of specific IgG “blocking antibodies” put forth by Robert A. Cooke in 1935 [202]. Twenty years later, Cooke and his colleagues confirmed in ragweed-treated patients via electrophoretic mobility studies that this factor was γ-globulin [203]. While the blocking antibody concept fell out of favor for a time, it, once again, has been convincingly demonstrated by other investigators, including Stephen Durham and his colleagues, that induction of IgG4 is an important part of the humoral response in grass allergen immunotherapy [204]. Though unproven, induction of allergen-specific IgG4 likely allows allergen capture prior to binding mast cell and basophil-bound IgE. Beyond the blocking antibody concept, however, the regulatory T cell is also implicated as a central event in the induction of allergen tolerance to allergen immunotherapy. These regulatory T cells produce two critical immunosuppressant cytokines, IL-10 and TGF-β. Akdis and colleagues first recognized the fundamental importance of IL-10, which Chen and colleagues extended by demonstrating that TGF-β is required for the FOXP3-mediated conversion of naïve CD4+ CD25− T cells into the CD24+ CD25+ regulatory T-cell type [205,206]. The regulatory T-cell induction also causes a skewing toward a Th1 versus a Th2 response commonly associated with atopic phenotypes. Both the reemergence of the importance of the blocking antibody IgG4 and the central role of the regulatory T-cell response are important milestones in the understanding of how to induce a tolerogenic state in allergic individuals.
New pharmaceutical approaches for the treatment of food allergies
Published in Expert Opinion on Drug Delivery, 2018
Ana Brotons-Canto, Nekane Martín-Arbella, Carlos Gamazo, Juan M. Irache
In summary, FA, defined as an adverse immune response to food proteins, affect to an increased percentage of population. Currently, management of FA consists of educating the patient to avoid ingesting the responsible allergen and initiating therapy if accidentally this ingestion occurs. In the last years, novel therapeutic approaches have been proposed including allergen-specific immunotherapies (oral, sublingual, or cutaneous administration) and immunomodulatory treatments (e.g. monoclonal antibodies, probiotics, etc.). Allergen immunotherapy involves the administration of daily small amounts of an allergen over long periods of time (up to some years), that compromise the adherence of patients to the treatments. In addition, these immunotherapy treatments would not offer adequate tolerogenic immune responses. In order to solve these drawbacks, the association of allergens with nanoparticulate adjuvants would be an adequate approach to develop more effective and safer treatments. Thus, nanoparticles can be designed to reach the gut epithelium and, taken into account their inherent inclination to be naturally captured by APCs, facilitate the development of tolerance by promoting strong and lasted Th1 responses. On the other hand, immunomodulatory treatments based on monoclonal antibodies have been proposed in order to block the allergic response. Nevertheless, in spite of the significant progress developed in the last years, there is still much to be done to offer these new approaches to FA patients.
Presentation, diagnosis, and the role of subcutaneous and sublingual immunotherapy in the management of ocular allergy
Published in Clinical and Experimental Optometry, 2021
Amruta Trivedi, Constance Katelaris
The general proposed mechanism of action of allergen immunotherapy and induction of immune tolerance is shown in Figure 3. Immunotherapy or desensitisation leads to induction of regulatory T cells, which release interleukin‐10 and transforming growth factor beta, which then cause early suppression of mast cells, basophils, and eosinophils, thereby reducing release of their pro‐inflammatory mediators following aeroallergen exposure. Interleukin‐10 and transforming growth factor beta also suppress T‐helper‐2 cells, which are critically involved in allergic diseases, and also suppress inflammatory dendritic cells, while inducing tolerogenic dendritic cells. Finally, interleukin‐10 and transforming growth factor beta promote immunoglobulin class switching, by promoting production of IgG4 and IgA, which compete with IgE for allergen binding, thereby limiting the IgE mediated activation and degranulation of mast cells and basophils that cause the allergic response.
What are the effects of rhinitis on patients with asthma?
Published in Expert Review of Respiratory Medicine, 2019
Amelia Licari, Sara Manti, Giorgio Ciprandi
To date, allergen immunotherapy represents the only disease-modifying treatment for IgE-mediated AR [16,17]. Via its capacity to modulate allergic inflammation [18], allergen immunotherapy has been recently approved as add-on treatment in house dust mite-sensitized asthmatic patients with coexisting AR, showing a forced expiratory volume in 1 s (FEV1) major than 70% predicted and reporting exacerbations despite inhaled corticosteroids therapy. Evidence documented that allergen immunotherapy improves asthma symptoms and bronchial hyperresponsiveness, and it decreases the need for pharmacotherapy in the short term. Moreover, allergen immunotherapy has been associated with a lower AR and asthma progression as well as a less frequent asthma onset [16,19].
Related Knowledge Centers
- Allergen
- Allergic Conjunctivitis
- Allergic Rhinitis
- Asthma
- Rhinitis
- Sublingual Administration
- Anaphylaxis
- Allergy
- Meta-Analysis
- Side Effect