Hymenoptera venom allergy
Apis mellifera or honeybee venom (HBV) is the best-characterized
Hymenoptera venom due to the outstanding importance of this species as
elicitor of venom allergy worldwide. Detailed genomic information and
proteomic data of the pure venom is
available8081-83. So far 12
allergens of HBV are identified84. Only two of them
present substantial amounts in the venom, the major allergen
phospholipase A2 (Api m 1)(12%) and the minor peptidic allergen
melittin (Api m 4)(50%)85. Despite their lower
abundance in HBV compared to Api m 1, a role as relevant major allergen
was also confirmed for Api m 2 (hyaluronidase), Api m 3 (acid
phosphatase), Api m 5 (dipeptidylpeptidase IV) and Api m 10 (icarapin)
with sIgE reactivity in the range of 47.9-52.2%, 49.6-50%, 58.3-61.7%
and 61.8-72.2% of allergic patients’ sera, respectively86,87.
For the other HBV allergens less information about sensitization rates
is available 88-90.
Some HBV allergens have been identified as risk markers of more severe
clinical phenotypes such as Api m 4 or of venom immunotherapy (VIT)
failure such as Api m 1086,91.
Prominent Vespula spp. (known as yellow jackets in the USA)
allergens include phospholipase A1 (Ves v 1), hyaluronidase (Ves v
2.0101) and antigen 5 (Ves v 5)92,93.
A second hyaluronidase (Ves v 2.0201), carrying an inactivation mutation
in the active site of the enzyme, was identified, which seems to be the
predominant isoform94,95.
Yellow-jacket venom (YJV) also contains a dipeptidylpeptidase IV (Ves v
3) which shows high homology to HBV Api m 596. The sensitization
rates of YJV-allergic patients to Ves v 1, Ves v 3 and Ves v 5 are
33.3-54% 97-102,
50-62.8%96,97and 84.5-100%, respectively97,99,100,102-104.
In contrast to HBV hyaluronidase Api m 2, which is a major allergen, the
YJV homologue Ves v 2 seems to be of restricted relevance and
sensitization was reported in 5-25% of YJV-allergic patients105.
The allergen composition of Polistes dominula venom (PDV) is very
similar to that of YJV and the most important allergens are
phospholipase A1 (Pol d 1), dipeptidylpeptidase IV (Pol d 3) and antigen
5 (Pol d 5) with sensitization rates of 87%106, 66.7%107 and 69-72%106, respectively.
CRD is helpful to discriminate between genuine double sensitization and
cross-reactivity, allowing physicians to optimize patient selection for
VIT. The potential of CRD becomes evident by the fact that HBV and YJV
in addition to homologous allergens also contain differentiating marker
allergens that are present in either HBV or YJV. This is not the case
when differential diagnosis between Vespula spp . andPolistes spp . is required (Figure 6). CRD is also helpful in
identifying patients with Hymenoptera venom-induced anaphylaxis having
negative test results to whole venom extracts, as it can be the case in
hymenoptera venom-allergic patients with mast cell disorders108. Currently
available allergens of honeybee and vespid venoms (see Table 2) allow a
molecular diagnosis in the vast majority of patients, but not in 100%
of them. Moreover, not all allergens are available for one assay system.
New recombinant molecules are needed to improve the diagnosis ofPolistes spp .-allergic patients, especially in the case of
double-positivity to both Polistes spp . and Vespula spp .
venom, in order to prevent unnecessary double VIT (Figure 7A). Although
diagnostic sensitivity of the currently available allergen panel,
particularly of HBV, is not 100%, CRD has clearly improved
discrimination of primary allergy and cross-reactivity in YJV and HBV
allergy, thus facilitating correct prescription of VIT. A suggested
diagnostic algorithm to discriminate between HBV and YJV allergy using
CRD is given in Figure 7B. Of note, the same algorithm using the
corresponding PDV allergens can also be applied to discriminate between
HBV and PDV allergy.