Specific Immunotherapy
How it works

Allergen-specific immunotherapy (SIT, hyposensitisation, desensitisation, allergy vaccination) is the only causal treatment for allergies to unavoidable allergens. It involves the administration of increasing doses of allergens with the aim of ameliorating the allergic response [1].

Type I allergic diseases, including allergic rhinoconjunctivitis and allergic asthma, are characterised by an imbalance between two subpopulations of T-lymphocytes, type 1 and type 2 helper T-cells (TH1 and TH2 cells) [1]. These two types of T-cells differ in the nature of the cytokines produced and released outside the cells – cytokines being immune system messengers that trigger a specific response. In allergic patients, TH2 cells are the predominant subpopulation upon contact with an allergen, and these produce mostly interleukins (IL-4, IL-5 and IL-13). These cytokines in turn cause other cells of the immune system to release immunoglobulin E (IgE), leading to the development of allergic symptoms following exposure to allergens.

In healthy individuals, there is a balance between the different TH cell populations, resulting in suppression of allergen-specific IgE synthesis. Cytokines produced by regulatory T-cells (T-regs) such as IL-10 and transforming growth factor beta (TGF-β) contribute toward this suppression, but IFN-γ, a cytokine produced by TH1 cells, also inhibits the synthesis of typical TH2 cytokines. IgG antibodies are formed upon contact with the allergen, and there is no allergic reaction.

T-regs have an important role in a balanced immune response upon exposure to foreign protein (= allergen for an allergic patient). This T-lymphocyte subpopulation, which has only recently been studied in greater detail, also has a central role in the therapeutic effect of specific immunotherapy. In allergy sufferers, T-regs are activated by repeated allergen administration during SIT. This effect is mediated by antigen-presenting cells (APCs) in body tissues. APCs take up allergen, break it down into smaller fragments (peptides), and then present some of these fragments to allergen-specific T-cells. This process also involves the induction of T-regs whose cytokine spectrum has a central impact on whether TH cells differentiate more into TH1 cells or preferentially into TH2 cells.

The allergen dose largely determines the response of T-regs: if a high allergen concentration is presented to APCs, they cause T-regs to produce cytokines IL-10 and TGF-β, directing the immune response to the allergens toward a “healthy” TH1 response [2;3]. A low allergen concentration predominantly induces a TH2 cytokine profile. When an allergy patient is regularly exposed to high doses of their particular allergen, T-regs are repeatedly activated, resulting in a cytokine pattern switch: IL-4 and IL-5 production decreases, and IFN production increases. This in turn changes the pattern of allergen-specific immunoglobulins. Over the long term, specific immunotherapy results in reduced formation of allergen-specific IgE and increased IgG production, causing the allergy symptoms to reduce [2].

Immunologic effects

SIT-induced immunologic effects can be measured. Increased production of IgG4 antibodies is an important marker of immunologic realignment processes [2]. These IgG antibodies are called “blocking antibodies” because they inhibit the interaction between allergens and IgE antibodies, thus contributing toward the efficacy of SIT. Specific immunotherapy also has effects on immunologic/allergologic effector cells in tissues: histamine release from basophils is inhibited [4] and eosinophil migration into the skin and mucous membranes is reduced, thus lessening the allergic inflammatory response [5;6]. Patients will experience relief of symptoms [2;4]. In clinical trials, the success of SIT has been objectified by measurements of reduced migration of eosinophilic and IgE-positive cells into the nasal mucosa [7]. In addition, reductions in marker proteins of inflammation (tryptase, ECP) in nasal secretions have been demonstrated following clinically successful SIT [6;8;9]. The immune response switch correlates with clinical efficacy [2;10].

Read more on the next page: "Indications, contraindications, interactions"

REFERENCES:
[1] Bousquet J, Lockey RF, Malling HJ. WHO Position Paper - Allergen immunotherapy: therapeutic vaccines for allergic diseases - Geneva, January 27-29,1997. Allergy 1998;53(Suppl.44):4-42.
[2] Akdis CA, Akdis M. Mechanisms of allergen-specific immunotherapy. J Allergy Clin Immunol 2011;127(1):18-27.
[3] Fiebig H. Allergenextrakte - Allergoide - Peptide. Allergologie 1997;20:599-606.
[4] Chyrek-Borowska S, Rogalewska A, Michalska I, Szymanski W. Basophil histamine release test in monitoring specific immunotherapy. Int Rev Allergol Clin Immunol 1995;1:12-6.
[5] Bachert C. Einfluss der spezifischen Immuntherapie bei Nasenschleimhautentzündungen. Allergo J 1997;6:157-8.
[6] Hauser U, Wagenmann M, Rudack C, Cromwell O, Ganzer U. Specific immunotherapy suppresses IL-1b and IL-8 levels in nasal secretions: a possible explanation for the inhibition of inflammatory cell migration. Otorhinolaringol Nova 1997;7:31-9.
[7] Hauser U, Bachert C, Frank E. Hemmung des Einstroms von Entzündungszellen in die Nasenschleimhaut durch die allergen-spezifische Immuntherapie. Allergo J 1995;4:164-71.
[8] Klimek L. Einfluss der Immuntherapie auf Symptomatik, Zellaktivierungsmarker und inflammatorische Mediatoren bei allergischer Rhinitis. Allergo J 1997;6:158-60.
[9] Werfel T. Marker der allergischen Entzündung in Sekreten und im Serum. Allergologie 1997;20:481-3.
[10] Malling HJ, Weeke B. Position Paper - Immunotherapy. (EAACI) The European Academy of Allergology and Clinical Immunology. Allergy 1993;48(Suppl. 14):9-35.