Allergenspecific Immunotherapy: History, Current Views and Problems

M.I. Derkach, V.V. Chopyak

Abstract


As you know, the most common form of allergic reactions is the so-called IgE-mediated hypersensitivity, which, according to various authors, occurs in 25 % of the population of industrialized countries [1].
It is commonly known that the method of allergenspecific immunotherapy (ASIT) includes a re-introduction of sensitizing allergen, usually by subcutaneous injection, or, as it have been proposed recently, sublingual [8].
Some recent studies confirm the role of dendritic cells in the induction of a population of CD4+ T lymphocytes capable in large quantities to produce IL-10, which in modern literature designated by the term «T-regulatory cells» (Treg1) of the phenotype and functional properties of T-lymphocyte helper. According to many authors, the emergence of a population of regulatory cells is probably a major positive outcome during ASIT [15]. However, this antigen presentation of causal antigen immature dendritic cells causes increased production of IL-10 Treg1 cells that eventually over time leads to a weakening of allergic inflammatory response. ASIT recent clinical trials have shown that increasing the concentration of IL-10 may be due to the direct synthesis of other cytokines antigen-presenting cells (B-lymphocytes, monocytes and macrophages) and the formation of this background generate IL-10-secreting Treg1 cells [16].
It was found that Treg1 cells in response to the impact of house dust mite allergen and birch pollen in the mucous membranes of the upper respiratory tract produce IL-10 and TGF-β. These subclasses regulatory cells were labeled Th3-cells. Treg1 cells induced activation of Toll-like receptors, are able to produce mainly IL-10 with a small amount of IFN-γ, and Treg1 cells induced by Hymenoptera venom allergens, in response to ongoing ASIT predominantly produce IL-10 [19]. Thus, it appears that multiple Treg1 cells are heterogeneous and depending on the influence of the microenvironment can produce different combinations of cytokines.
At that time, as earlier studies indicated the shift from Th2-type cellular response to systemic Th1-response in patients with late stage allergic reaction in the skin and mucous membranes, most current research indicates that ASIT pollen allergens leads to an increase in mucosa Treg1 peripheral cells capable of synthesizing IL-10 and TGF-β. The local presence of CD4+ CD25+ Treg1 cells in the nasal epithelium and an increase in their number after ASIT performed directly confirm the role of these cells in the induction and maintenance of tolerance allergenspecific. The increase in the number of these cells correlates with the clinical efficacy of ASIT and a decrease in seasonal allergic inflammation [20].
Based on the above key role in the formation of immunological tolerance during ASIT given IL-10, a key cytokine can regulate the synthesis antigen-specific IgG and IgE. Thus IL-10 is a potent immunosuppressive factor for the development of both general and allergenspecific IgE. High concentrations of IL-10 lead to a systematic increase in plasma cells producing immunoglobulin G4 (IgG4). Thus, IL-10 can not only induce T-cell immunologic tolerance, but also regulate the formation of isotype-specific plasma cells with changing profile of highly specific responses to allergen with IgE-dependent on IgG4-dominant immune response.
It was noted that in the process of ASIT in patients with allergy to house dust mite antigens for 70 days after treatment showed a significant increase of serum IgA and IgG4, which coincides with an increase in the concentration of IL-10 and TGF-β. This largely explains the associative role of IgA and TGF-β, and IgG4 and IL-10 in the formation of peripheral immunological tolerance when exposed to allergens in healthy individuals. It is possible that the decline in the value IgE/IgG4 of ASIT reflects the formation of cell allergenspecific deviation from Th2-cells to Treg1 cell population.
Much of the time during the series ASIT, probably goes to the depletion clone allergenspecific long-lived plasma cells, whose service may be another target for the additional concomitant immunomodulation.
Monitoring of patients who are allergic pathology, Western regional center of clinical immunology and allergology 10 years have shown that the number of IgE-dependent diseases accounted for 72.3 % of the total surveyed 5845 patients. The vast majority of patients were suffering from hay fever — 91.8 %, allergic rhinosinusitis — 84.7 %, atopic dermatitis — 70.2 %, asthma — 58.6 %, urticaria — 54.8 %, other IgE-dependent diseases/response — 50.8 %. Conducting allergenspecific diagnosis identified the need for SIT and ASIT. Unfortunately, the percentage of patients who received this type of therapy was only 5.3 %. The reasons for this low level of this type of treatment a lot, and in modern terms with the need of a wider study allergist and the patients to change their attitude towards the use of SIT and ASIT especially as evidence of treatment IgE-dependent allergic diseases with level of evidence A.


Keywords


allergenspecific therapy; IgE; dendritic cells; IL-10; Treg1 cells

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DOI: https://doi.org/10.22141/2224-0721.6.54.2013.84647

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