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i210 rPol d 5
Recombinant protein Antigen 5, Polistes
dominulus (Paper wasp)
Clinical Utility
rPol d 5 is a marker for primary sensitization
to Vespidae venom, and particularly to Polistes.
ImmunoCAP ® Allergen component i210, rPol d 5
is a valuable diagnostic tool to identify whether or not
the culprit insect is a Paper wasp when assessing allergic
reactions in stung patients. This is of particular clinical
value when immunotherapy is considered.
Allergen Description
Pol d 5, known as antigen 5, is a 23 kDa protein from the
species Polistes dominulus. Its biological function is as yet
unknown. Antigen 5 is recognised as the major and most
potent allergen in venoms of the Vespidae family, i.e. Paper
wasp, Common wasp and European hornet (1-4). It is not
found in honeybee venom (5-6).
Cross-Reactivity
Homologues of antigen 5 from different wasps, hornets
and paper wasps are known (4-5, 7-8). A sequence
similarity of approximately 98% occurs within P.
dominulus and P. gallicus, which are European species
of Polistes (9). This figure falls when comparing Polistes
from Europe with those from the US, and even more
when antigen 5 is compared between different genera
(3-4, 9-13). Antigen 5 displays 69% and 60% sequence
identity with the homologue proteins of Dolichovespula
maculate and Polistes annularis respectively, for example
(4, 8). Note that structural similarity between proteins
suggests but does not guarantee clinical cross-reactivity
for all patients.
Antigen 5 has also been found in venoms from different
ants, and great variation in protein sequence similarity to
homologue proteins of different Vespidae species has been
demonstrated (6, 14).
Clinical Experience
The most common reactions to stings from different
stinging insects are large local reactions and systemic
anaphylactic reactions, the latter most often IgEmediated.
Self-reported systemic reactions range from
0.3% to 7.5% (15).
When people stung by bees or wasps experience severe
reactions, identifying the culprit insect is very important.
This is particularly true if a patient is considered for
venom immunotherapy (VIT). Some patients are allergic
to more than one stinging insect, whereas others are only
allergic to one species. In many cases, this is difficult to
establish correctly since patients have difficulty recognising
the different species, and also because double-positivity is
a quite frequent problem when testing for IgE antibodies
to honeybees and/or different wasps (12, 15-18).
Double-positivity is caused by:
- true double-sensitization to honeybee and wasps,
or different wasps,
- sensitization to cross-reacting allergen proteins
present in venoms of different species,
- sensitization to CCD (carbohydrate determinants)
present in venoms of different species.
Within the Vespidaes, Vespula and Vespa are closely
related, whereas Polistes is more distantly related.
Accordingly, there is limited cross-reactivity between
Polistes venom proteins and the other venom proteins
due to differences in the epitopes on the allergen proteins
(9).
In the Mediterranean region, multiple-positivity to IgE
tests for specific IgE to Vespula and Polistes is a diagnostic
problem (18-19). One study from Italy investigated
the degree of cross-reactivity between Vespula and
Polistes venoms. By using inhibition studies, the authors
concluded that a double sensitization to the venoms was
likely a result of cross-reactivity in 31 of 45 patients. All
45 had been prescribed VIT to both Vespula and Polistes,
and this study showed that immunotherapy with only
one venom extract would have been sufficient for 31 of
them (18).
The difference in allergenicity of the American Polistes
species and the European is also highlighted in studies. It
was concluded that the European Polistes (P. dominulus
and P. gallicus) venoms have exclusive allergens and that
proteins from these venoms are necessary in the diagnosis
of European patients (12). The clinical implication of
this conclusion was shown in a report on the ineffective
treatment with American Polistes venom of an Italian
patient allergic to European Polistes (20).
Access to rPol d 5 and other venom-specific allergen
markers will thus aid in selecting patients for VIT.
Furthermore, it will allow monitoring of the patients’
specific IgE reactivity during the treatment period (21).
Family
Subfamily
Genus
Species
(examples)
Vespula
Wasp - EU
Yellow jacket - US
V. germanica
V. vulgaris
V. maculifrons
V. pennsylvanica
Vespinae
Dolchovespula
Wasp - EU
Hornet - US
D. sylvestris
D. maculata
D. saxonica
Vespidae
Wasps
Vespa
Hornet - EU
Eu. Hornet - US
Figure 1. Classification and common names of Vespidae
(wasps). Figure adapted from Fernandez J, 2004 (19) and
Bilo BM et al, 2005 (15).
Polistinae
Polistes
Paper wasp
V. crabo P. dominulus
P. gallicus
P. exclamans
P. annularis
Photo: Wikipedia

References
1. Bohle B, Zwolfer B, Fischer GF, Seppala U, Kinaciyan T,
Bolwig C, Spangfort MD, Ebner C.
Characterization of the human T cell response to
antigen 5 from Vespula vulgaris (Ves v 5).
Clin Exp Allergy 2005;35(3):367-73.
2. Hoffman DR.
Allergens in Hymenoptera venom. V. Identification of
some of the enzymes and demonstration of multiple
allergens in yellow jacket venom.
Ann Allergy 1978;40(3):171-6.
3. Hoffman DR.
Allergens in Hymenoptera venom XV: The
immunologic basis of vespid venom cross-reactivity.
J Allergy Clin Immunol 1985;75(5):611-3.
4. Hoffman DR.
Allergens in Hymenoptera venom. XXV: The amino
acid sequences of antigen 5 molecules and the
structural basis of antigenic cross-reactivity.
J Allergy Clin Immunol 1993;92(5):707-16.
5. Henriksen A, King TP, Mirza O, Monsalve RI, Meno K, Ipsen H,
Larsen JN, Gajhede M, Spangfort MD.
Major venom allergen of yellow jackets, Ves v 5:
structural characterization of a pathogenesis-related
protein superfamily.
Proteins 2001;45(4):438-48.
6. King TP, Guralnick M.
Hymenoptera allergens, In Allergens and Allergen
Immunotherapy.
Lockey R, Bukantz S, Bousquet J, Eds. Marcel Dekker,
New York 2004:339-54.
7. Lu G, Villalba M, Coscia MR, Hoffman DR, King TP.
Sequence analysis and antigenic cross-reactivity of a
venom allergen, antigen 5, from hornets, wasps, and
yellow jackets.
J Immunol 1993;150(7):2823-30.
8. Tomalski MD, King TP, Miller LK.
Expression of hornet genes encoding venom allergen
antigen 5 in insects.
Arch Insect Biochem Physiol 1993;22(3-4):303-13.
9. Pantera B, Hoffman DR, Carresi L, Cappugi G, Turillazzi S,
Manao G, Severino M, Spadolini I, Orsomando G, Moneti G,
Pazzagli L.
Characterization of the major allergens purified from
the venom of the paper wasp Polistes gallicus.
Biochim Biophys Acta 2003;1623(2-3):72-81.
10. Monteiro MC, Romão PR, Soares AM.
Pharmacological perspectives of wasp venom.
Protein Pept Lett 2009;16(8):944-52.
11. King TP, Lu G, Gonzalez M, Qian N, Soldatova L.
Yellow jacket venom allergens, hyaluronidase and
phospholipase: sequence similarity and antigenic
cross-reactivity with their hornet and wasp homologs
and possible implications for clinical allergy.
J Allergy Clin Immunol 1996;98(3):588-600.
12. Severino MG, Campi P, Macchia D, Manfredi M, Turillazzi S,
Spadolini I, Bilo MB, Bonifazi F.
European Polistes venom allergy.
Allergy 2006;61(7):860-3.
13. Sanchez F, Blanca M, Fernandez J, Miranda A, Terrados A,
Torres MJ, Del Cano A, Garcia JJ, Juarez C.
Comparative study between European and American
species of Polistes using sera from European sensitized
subjects.
Clin Exp Allergy 1995;25(3):281-7.
14. Lee EK, Jeong KY, Lyu DP, Lee YW, Sohn JH, Lim KJ, Hong CS,
Park JW.
Characterization of the major allergens of
Pachycondyla chinensis in ant sting anaphylaxis
patients.
Clin Exp Allergy 2009;39(4):602-7.
15. Bilo BM, Rueff F, Mosbech H, Bonifazi F, Oude-Elberink JN.
Diagnosis of Hymenoptera venom allergy.
Allergy 2005;60(11):1339-49.
16. Hemmer W, Focke M, Kolarich D, Wilson IB, Altmann F, Wöhrl S,
Götz M, Jarisch R.
Antibody binding to venom carbohydrates is a
frequent cause for double positivity to honeybee and
yellow jacket venom in patients with stinging-insect
allergy.
J Allergy Clin Immunol 2001;108(6):1045-52.
See i209 Api m 1 product leeflet.
17. Muller UR, Johansen N, Petersen AB, Fromberg-Nielsen J,
Haeberli G.
Hymenoptera venom allergy: analysis of double
positivity to honey bee and Vespula venom by
estimation of IgE antibodies to species-specific major
allergens Api m 1 and Ves v 5.
Allergy 2009;64(4):543-8.
18. Caruso B, Bonadonna P, Severino MG, Manfredi M, Dama A,
Schiappoli M, Rizzotti P, Senna G, Passalacqua G.
Evaluation of the IgE cross-reactions among vespid
venoms. A possible approach for the choice of
immunotherapy.
Allergy 2007 May;62(5):561-4.
19. Fernandez J.
Distribution of Vespid species in Europe.
Curr Opinion Clin Immunol 2004;4:319-24.
20. Bonadonna P, Caruso B, Labardi D, Dama A, Senna G,
Passalacqua G.
Treatment with American Polistes venom was
ineffective in an Italian patient allergic to European
Polistes.
Allergy 2007;62(8):966-7.
21. De Graaf DC, Aerts M, Danneels E, Devreese B.
Bee, wasp and ant venomics pave the way for a
component-resolved diagnosis of sting allergy.
J Proteomics 2009;72(2):145-54.
For further reading, see: www.immunocapinvitrosight.com
Phadia AB. P O Box 6460, SE-751 37 Uppsala, Sweden
Tel +46 18 16 50 00. www.phadia.com
March 2010