Elucidation of the mechanism of immune tolerance in beekeepers

Along with drugs and food, insect venom constitutes the major reason for the pathogenesis of anaphylaxis. The Hymenoptera insect group includes Apidae, Vespidae and Formicidae subgroups. Among these, Apidae-honeybees (Apis mellifera) and bumblebees (Bombus spp.) and Vespidae-the common wasp (Vespula vulgaris) and European hornet (Vespa crabro) cause allergic reactions (1, 2). Allergy to honey bee venom is especially prevalent in beekeepers and their family members (3). Nearly a quarter of the anaphylactic reactions reported in Europe are caused by the stings of bees (4). Over 20 patients per year with a diagnosis of anaphylaxis to bee venom are seen in the Peninsula Allergy service at UHP.
Hymenoptera venoms are complex mixtures of various substances including numerous relevant allergens. The amount of venom that is injected during a sting is species specific. Honeybees inject up to 140 microgram of venom, with protein content of around 59 microgram (5, 6). In contrast to airborne allergens that have to cross mucosal barriers, venom allergens are injected into the skin and reach the blood easy and fast. Hymenoptera stings may cause both local and systemic allergic reactions including life threatening anaphylactic reactions. Transient pain, itching and swelling are part of the normal response to hymenoptera stings due to irritative and toxic venom components.
Although severe anaphylactic reaction leading to death following bee stings is rare, it is a concern to all beekeepers as it is not possible to predict when or if an individual might be affected. To date no parameter has been identified that may predict which sensitized people will have a future systemic sting reaction (SSR) (8). Venom immunotherapy (VIT) is the most effective method of treatment for people who had SSR, which remains effective even after discontinuation of therapy. Development of peripheral tolerance is the main mechanism during immunotherapy and the contribution of regulatory T (Treg) cells in it have been reported (9, 10). However, the detailed cellular and molecular mechanism in establishing tolerance to hymenoptera stings in general and to bee stings in particular are far from clear. Investigating these details will certainly help in predicting the occurrence of allergic reactions and its likely severity in advance and facilitate a better clinical management of allergic patients.

References
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(i) The distribution and function of various T cell (CD4+, CD8+ and Treg etc.) populations in the healthy control, tolerant and allergic population, and
(ii) The molecular mechanism and the epigenetic regulation of establishment of immune tolerance in tolerant beekeepers.