i216 Api m 5

Summary  

Api m 5, a glycoprotein of the venom dipeptidyl peptidase IV (DPPIV) family, is a major allergen of Apis mellifera (honeybee) venom (HBV). It exhibits cross-reactivity with homologous Vespid venom DPPIV allergens. 

Epidemiology

Worldwide distribution

Api m 5 sensitization has a prevalence of 16% to 70% among HBV-allergic populations (reviewed in [1]). Thus, Api m 5 is considered a major allergen in HBV-allergic patients.

Environmental characteristics

Source and tissue

Api m 5 is secreted into the venom sac of Apis mellifera, where it contributes less than 1% of venom dry weight [2]. 

Risk factors

Sensitization to Api m 5 occurs through injection (bee sting). 

Clinical relevance

Cross-reactive molecules

Api m 5 belongs to the DPPIV family of allergens, which is widespread among Hymenoptera and contributes to cross-reactivity between these venoms [1, 2]. 

Disease severity

Various patterns of sensitization to HBV allergens have been described, but no clinical correlate of severity has been identified so far [1].

Molecular aspects

Biochemistry

Api m 5, also known as venom DPPIV, is a secreted glycoprotein with a molecular weight of 100 kDa (775 aminoacids), N-glycosylated side chains and disulfide bonds [1, 3, 4]. It cleaves N-terminal dipeptides, one of its substrates being promelittin thus generating the active melittin molecule [1].

Isoforms, epitopes, antibodies

As of July 5, 2023, a unique isoallergen, Api m 5.0101, has been included in the World Health Organization (WHO) and International Union of Immunological Societies (IUIS) Allergen Nomenclature [5]. 

Cross-reactivity due to structural similarity

Api m 5 and its Vespid counterparts such as Ves v 3 and Pol d 3 exhibit clinically relevant cross-reactivity [1].

Diagnostic relevance

Cross-reactivity between HBV and Vespid venoms

Cross-reactivity between Api m 5 and its homologous Vespid DPPIV allergens contribute to the double-positivity to HBV and Vespid venom whole extracts [1, 6].

Disease Severity

In Hymenoptera IgE testing, the quantitative result of specific IgE to a molecular allergen or whole venom extract is neither predictive of, nor correlated to the severity of the reaction [1]. 

Sensitivity of in vitro assays

The prevalence of sensitization to individual HBV allergens, including Api m 5, in HBV-allergic patients varies depending on multiple factors such as geography, patient inclusion criteria, single or double positivity to HBV and Vespid venoms, underlying sensitization profile, use of a recombinant allergen versus a natural purified allergen, and the assay format [1, 7, 8]. Thus, the diagnostic sensitivity of specific IgE to rApi m 5 ranges from 16 to 70% in HBV-allergic patients [1].  Using a panel of HBV allergens including rApi m 5 besides available HBV marker allergens Api m 1, Api m 3, and Api m 10 improves the rate of confirmation of genuine HBV sensitization [1, 7, 8]. 

Api m 5 sensitization can be detected with commercially available singleplex methods.

Diagnostic specificity

The diagnostic specificity of IgE to rApi m 5 in HBV-allergic patients was reported as 100% when compared to HBV-negative controls [7]. Detectable rApi  5-specific IgE were found in 3/40 (7.5%) cases of Vespid venom allergic patients without HBV allergy, and in 2/6 (30%) of nonallergic controls sensitized to HBV extract [8]. 

Compiled by:

Author: Prof. Joana Vitte

Reviewer: Dr. Merima Mehic Chaveton