Allergen-specific immunotherapy: is it vaccination against toxins after all?

Abstract

IgE-mediated allergies, in particular allergic rhinoconjunctivitis and asthma, have reached epidemic proportions, affecting about one-third of the population in developed countries. The most effective treatment for allergies is specific immunotherapy (SIT), which involves the injection of increasing doses of an allergen extract to allergic individuals. The current form of SIT was first introduced in 1911 and recently celebrated its 100th birthday for the treatment of hay fever. The concept of this therapy at the time was straightforward, as it was believed that pollen contained toxins against which the patient could be vaccinated. However, the understanding became blurred with the discovery that IgE antibodies were the effector molecules of the allergic response. Subsequent research focused on the idea that SIT should induce tolerance keeping the IgE antibodies at bay. In this review, we will discuss the various hypotheses for the mechanism of SIT and we will put forward the concept that allergens may be viewed as 'protoxins' which need to be activated by IgE antibodies. Within this framework, protoxin-neutralizing antibodies are the key effector molecules while a shift to Th1 or Treg cells mainly contributes to the efficacy of SIT by helping B cells to produce neutralizing IgG antibodies.

Identification of specifically reduced Th2 cell subsets in allergic rhinitis patients after sublingual immunotherapy

“…The suppression of these IL‐5‐producing memory Th2 cells might lead to suppression of allergic inflammation, including the activation of eosinophils. Although the mechanism of specific suppression of ST2 + Th2 cells during SLIT is unclarified, the suppressor cells such as tolerogenic dendritic cells, Treg cells and regulatory B cells induced by SLIT might be involved …”

Allergens displayed on virus‐like particles are highly immunogenic but fail to activate human mast cells

“…Patients are exposed to multiple doses of the allergen, causing the immune system to tolerate the allergens better . There is an ongoing discussion about the most important effector mechanisms causing this state of increased “tolerance” but it is generally accepted that induction of allergen‐specific IgG correlates with reduced symptoms and is taken as evidence for successful therapy …”

Skin Test Reactivity to Hymenoptera Venom after Venom Immunotherapy Correlates Inversely with the IgG/IgE Ratio

“…IgG also binds the inhibitory FcεRIIb receptor on mast cells and abrogates mast cell activation by IgE [32] . However, a correlation between increased IgG after VIT and protection from allergic reactions after future stings has not yet been proven [33] . This might be due to the possibility that not all IgGs bind to epitopes on allergens that are recognized by IgE, hence allergen recognition by IgE is not totally blocked despite high IgG levels [34] .…”