The evolution of allergy immunotherapy

Abstract

Recognition of hay fever as a distinct entity coincided with the marked increase in the prevalence of allergic diseases in the latter part of the 19th century. This probably reflected the improving levels of hygiene and the trend toward urbanization.Allergy immunotherapy (AIT) was practiced with a high level of enthusiasm for more than 4 decades before randomized, controlled studies scientifically established its efficacy. In the 6 decades since, well-designed studies have established its efficacy in seasonal and perennial allergic rhinitis, asthma, and Hymenoptera venom sensitivity.Studies have also established the principal humoral response to AIT to be the generation of specific immunoglobulin G4, whereas the cellular response is characterized early by the generation of a variety of regulatory T cells and later by an immune deviation from T H 2 to T H 1 response.With the efficacy of AIT established beyond question, including its role as the only disease-modifying treatment for allergic diseases, the onus now is to make AIT safer and more convenient for the patient so that more patients will benefit from this treatment.

Mechanisms of desensitization with oral immunotherapy and epicutaneous immunotherapy

“…These include the following: route of administration, dosing, duration for persisting benefit, evidence of disease modification, greater knowledge of the immunologic response(s) involved, efficacy of treatment with multiallergen mixtures, and safety and convenience. 2 The current immunologic mechanisms that contribute to the pathogenesis of the allergic disorders are presented together with the most up-to-date understanding of the immunologic mechanisms by which OIT and EPIT elicit desensitization. However, there still remain many questions and concerns to be addressed before these procedures can be fully understood.…”

“…Allergen immunotherapy (AIT) is a procedure first reported in 1911 by Gutermuth et al 1 for the treatment of hay fever, in which slowly increasing doses of a specifically relevant allergen are administered by subcutaneous cutaneous immunotherapy (SCIT) to an individual with an allergy until a maintenance dosage is achieved when the patient is free of symptoms. The aim of AIT is to induce unresponsiveness ( i.e., reduced immune reactivity) 2 or even a definitive absence of reactivity (tolerance) 3 to the offending allergen. The AITs for food allergies currently under study include oral immunotherapy (OIT), sublingual immunotherapy (SLIT), epicutaneous immunotherapy (EPIT), and SCIT.…”

Biomarkers in allergen immunotherapy: Focus on eosinophilic inflammation

“…The cellular and molecular mechanisms through which AIT act include suppression of inducible CD4(+), CD25+, and Treg cells, along with suppression of eosinophils, mast cells, and basophils and the switching of antibodies from IgE to IgG4 blocking antibodies (ie, the IgG4 antibody binds to the allergen without initiating an allergic reaction). A switch from a Th2 to a Th1 immune deviation has also been noted [ 38 ]. The main idea behind AIT is that gradually increasing doses of these allergenic extracts will desensitize the patient, leading to a reduction in symptoms and may even halt the development of new sensitizations.…”

A modified schedule of multiple aeroallergen ultra-rush immunotherapy in perennial allergic rhinitis: safety, efficacy, and T lymphocyte cell population studies

“…Suppression of high-affinity IgE receptor, FcεRI, activates basophils with selective suppression of H2 receptor-mediated histamine, and release of sulfide-leukotrienes (LTs) could be associated with fast induction of allergen tolerance and desensitization effect, particularly in venom immunotherapy. 24 Histamines are a low molecular weight monoamine components that bind to four different G-protein receptors with different effects on immune responses. Released histamine induces peripheral tolerance by several mechanisms.…”