i77 European paper wasp/Mediterranean paper wasp

Allergens within Venoms

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  • Latin name: Polistes dominulus
See also Paper wasp/Common paper wasp (Polistes exclamans, fasciatus, etc.) i4.
 
Venom
An insect, which may cause allergy symptoms in sensitised individuals.
 

Allergen Exposure

Geographical distribution
Insects of the order Hymenoptera are mainly responsible for causing allergic reactions from stings. However, only species belonging to 3 families sting people with a high degree of frequency: Bees (Apidae), Ants (Formicidae), and species of the family Vespidae, to which belong Wasps (Polistes), Hornets (Vespa/Dolichovespula), and Yellow jackets (Vespula) (1-4).

The genera Vespula, Dolichovespula and Vespa are found all over Europe. The genus Vespula predominates over Polistes and Vespa throughout Europe, except in Mediterranean areas. Polistes is the most common genus among social Wasps and has a worldwide distribution. In Europe and North America their colonies outnumber those of all other social Wasps combined (5); although they are present in central Europe, they are not found in the UK and are rare in northern Europe (4).

P. dominulus, P. gallicus, P. biglumis and, to a lesser extent, P. ninphus are the most widely spread in Europe and are especially relevant in Mediterranean areas, while P. annularis, P. fuscatus, P. metricus, P. apachus and P. exclamans are present in the USA (5-7). There are more than 20 species of Polistes found within the United States, the greatest diversity being in the southeast (7). The American species are not present in Europe. In 1981, P. dominulus (European species) was first reported in the Boston and New York City areas and has since spread across the continent. It is now the predominant Paper wasp found there (8-11). It has also been reported in Australia. Its invasive success is attributed to establishment of colonies earlier in the spring, reuse of abandoned nests, and a more varied diet than the native species has (12).

Recent systematic studies have confirmed that North American and European species of Polistes belong to different subgenera and are phylogenetically distant. The most common European species - P. dominulus, P. gallicus, P. nimphus and P. biglumis - belong to the subgenus Polistes sensu stricto, while the most common North American native species - P. exclamans, P. annularis, P. metricus and P. fuscatus - are included in the subgenera Aphanilopterus and Fuscopolistes (13-14).

The cross-reactivity between European and American Polistes is only partial (15). (See below)
 
Environment
Compared to other Hymenoptera, Paper wasps have a more primitive social organisation. The nests, with simple, single-layer paper cones, a maximum of about 100 cells, and no protective outer covering, are attached by a pedicle and have relatively low populations.

Fertilised queens hibernate during the winter in secluded places, but other wasps in the colony may visit the old nest on warmer days to access the honey caches there (16).

One queen (or several, but in this case there will be a single dominant egg-layer) starts a nest in the spring by laying eggs, and by late July there are up to 200 workers available. The first female workers tend to be sterile and smaller, but later broods are fertile, providing for several queens. Sexual larvae are produced starting in August, and in September adults (including the only recently produced males) leave the nest and mate outside (8-10, 12). Mated females then seek a safe place to hibernate. Polistes has a relatively simple life cycle, which is well suited to a warm climate such as in the Mediterranean (4).

Paper wasps tend to build nests on sheltered and little-used parts of buildings, placing humans in inadvertent danger of stings. Paper wasps can also be scavengers – often congregating around food factories and food shops - and this also brings them into human contact (8). They are, however, less aggressive than other members of the Vespidae. But it should be kept in mind that, whereas Bees lose their barbed stingers in a single attack and die, all Wasps, Hornets, and Yellow jackets can sting many times.
 

Unexpected exposure

See under Environment.
 
Allergens
The amount of venom released during a sting varies from species to species and even within the same species: Bee stings release an average of 50 ug (17) to 140 ug (18) of venom protein per sting; however, venom sacs may contain more than 300 ug of venom (19). Bumble bee stings release 10–31 ug of venom. In contrast, Vespinae, which are capable of repeated stings, generally inject less venom per sting: Vespula stings release 1.7–3.1 ug, Dolichovespula stings 2.4-5.0 ug, and Polistes stings from 4.2 to 17 ug of protein (17). One set of observations indicates that at least 90% of the venom sac content is delivered within 20 seconds, and that the venom delivery is complete within 1 minute, suggesting that a stinger must be removed within a few seconds after the sting to prevent anaphylaxis in an allergic person (18).

Though not all allergens in the venom of each vespid species have been characterised, 4 groups of allergens have been identified: group 1 is made up of forms of phospholipase A1, group 2 of hyaluronidase, group 4 of serine protease, and group 5 of antigen 5 (Ag5), a protein of uncertain function (20-22). The 3 most important allergens of venom from Wasps are hyaluronidase, phospholipase A1 and antigen 5. They have molecular weights of about 44, 36 and 22 kDa respectively (23).
  • Pol d 1, phospholipase A1, a lipase (24-26).
  • Pol d 4, a trypsin-like serine protease (24-25, 27-28).
  • Pol d 5, previously known as Ag5 or antigen 5 (24-25).

Isoforms:
Pol d 1.0101, Pol d 1.0102, Pol d 1.0103, Pol d 1.0104 (24).
Pol d 4.0101.
Pol d 5.0101.

A hyaluronidase allergen has been characterised in Pol e 2 (P. exclamans) and Pol a 2 (P. annularis), which suggests that a similar allergen exists in this species, but it has not yet been characterised there.

The protease Pol d 4 is important in European Polistes venom allergy and is also important in the American species (25, 29).

The biological function of antigen 5 (Pol d 5) is not known, although it has been reported that antigen 5 from Vespa mandarinia is a neurotoxin active at the neuro-muscular junctions of a Lobster walking leg (30).
 

Potential Cross-reactivity

Studies within the Polistes genus show extensive cross-reactivity among various species (6, 31-32). However, the European species of Polistes are different from those found in America. Significantly and surprisingly, the cross-reactivity between European and American Polistes is only partial, with significant differences in specificities (6, 11, 15, 25, 29, 33). Skin-specific IgE evaluation and direct RAST have confirmed these results (15). However, cross-reactivity is very strong between the 2 dominant species in Europe, P. dominulus and P. gallicus (25).

There is limited cross-reactivity between Polistes and other vespid venoms, since Polistes is not so closely related to Vespula, Dolichovespula and Vespa (among which there is a high degree of cross-reactivity). The cross-reactivity of Polistes is generally lower than that within Vespinae (4, 34-36).

Vespids (Wasps, Hornets, and Yellow jackets) each have unique as well as homologous venom allergens. The homologous venom allergens have varying degrees of sequence identity, ranging from about 60% for phospholipases and antigen 5s to about 80% for hyaluronidases. Amino acid sequence similarities between Polistes and other vespid allergens are less marked (1).

In general, phospholipases of Hornets, Yellow jackets and Wasps have 54 to 68% sequence identity, their hyaluronidases a 73 to 92% sequence identity, and antigen 5 a 58 to 67% sequence identity (1, 37).

The cross-reactivity of the phospholipase (PLA1) venom allergen can vary considerably. For example, PLA1s from 2 species of Yellow jackets, Vespula maculifrons and Vespula vulgaris, have 95% sequence identity with each other but only about 67 and 55% identity with White-face hornet and Paper wasp proteins, respectively (1, 38). There is, furthermore, limited cross-reactivity between Polistes and the other vespid venoms, because of differences in the epitopes on the allergen molecules (25). In a study of the major allergens (phospholipase, antigen 5, hyaluronidase and protease) of Polistes gallicus (European species) with those of Polistes annularis (American species), an 85% sequence identity was demonstrated between either Ag5, which increased to 98% within the same subgenus. The authors suggested that this may be a result of the common presence or of variations of specific epitopes on the Ag5 molecule (25). Still other studies have reported that there are multiple antigenic determinants on the phospholipase molecules, that individuals respond to different determinants, and that no general patterns of cross-reactivity could be observed (39).

Interestingly, the amino acid sequence of the phospholipase from Fire Ant, Sol i 1, compared with the sequences of 8 other venom phospholipases, had a higher homology with Pol d 1.01 (285 residues), as opposed to a 35% identity with Pol a 1 (209 residues) (40).

The protease allergens of Paper wasp, e.g., Pol d 4, are important. Although serine protease allergens from Honey bee, Bumble bee, and Paper wasp have been shown to have significant IgE binding activity, the structures are poorly conserved, suggesting little cross-reactivity (28).

Pol d 5, or Ag 5 (antigen 5), is a major allergen of vespid venom. A high degree of cross-reactivity of Hornet Ag 5 with Wasp or Yellow jacket Ag 5, and a low degree of cross-reactivity of Yellow jacket Ag 5 with Wasp Ag 5, was reported (41). Other studies have also reported varying degrees of cross-reactivity, as confirmed by varying patient responses, among homologous antigen 5 from a large number of different Yellow jackets, Hornets, and Paper wasps (42).

Ag 5s from Yellow jacket (Vespula vulgaris) and P. annularis (American species) have a 59% sequence identity and 69% with White-face hornet (Dolichovespula maculata), and low degrees of antigenic cross-reactivity in insect-allergic patients and in animal models (43-44). There is a greater degree of cross-reactivity among the homologous allergens of Hornets and Yellow jackets than among the homologous allergens of Hornets, Yellow jacket and Wasps (44). This is in the same order as that reported for the frequency of patients’ multiple sensitivity to these insects (45). However, a study investigating the degree of cross-reactivity between Vespula vulgaris and P. dominulus (European species) reported that in 31 of 45 patients, the double sensitisations to venoms were probably the result of cross-reactions (46).

However, apart from phospholipases (e.g., Pol d 1), antigen 5s (e.g., Pol d 5) are a major cause of the different immunological responses among American and European venoms. Although there is a 98% sequence identity between antigen 5 derived from the European species of Paper wasp P. dominulus and P. gallicus, the identity between the antigen 5 of P. gallicus and that of the American Paper wasps P. annularis and P. exclamans decreases to 85%; and although this is technically “high”, its relatively low level confirms the observed poor cross-reactivity between American and European Paper wasps (25).

Similarly, even though a high degree of homology could be shown between 2 forms of antigen 5 of Polybia scutellaris and those of other vespids, amino acids at positions 5 and 11 in the P. scutellaris antigens differed from the previously known sequences for antigen 5, suggesting that one or the other amino acid might be responsible for the lack of allergenicity of the P. scutellaris venom (47). This would confirm the variability of the antigenicity and cross-reactivity of antigen 5. Likewise, although Fire ant (Solenopsis invicta) contains an antigen 5 venom allergen, it lacks IgE cross-reactivity (48).

A hyaluronidase venom allergen found in other Wasps, e.g., Pol a 2 from P. annularis, has not yet been characterised for P. dominulus, but its presence can be expected. A 43-45 kDa hyaluronidase protein of Vespula vulgaris and similar proteins from 5 other Vespula Wasp species have been isolated and cloned, and found to have a 59% homology to P. annularis hyaluronidases (49).

Clinical expression of cross-reactivity between Vespula and Polistes venom allergens is illustrated in a study of 28 Spanish patients from Madrid and its surroundings, who had experienced systemic reactions to vespid stings. All patients had serum-specific IgE directed at Vespula venom, and half of them had it directed at Polistes venom. Polistes-specific IgE could be inhibited with either Polistes or Vespula venom to a similar degree; inhibition of Vespula-specific IgE was possible with Vespula venom, but only to a limited degree with Polistes venom. The authors concluded that in this geographic region sensitisation to Vespula venom was more common than to Polistes venom, and that Polistes may have cross-reactivity in these patients. Therefore, an individual can be sensitive to both venoms either due to a clinical sensitisation to both or due to common antigenic determinants (50).
 

Clinical Experience

IgE-mediated reactions
IgE-mediated reactions often present as large local manifestations, with swelling extending from the sting site, erythema, and pain.  Reactions may remain local, or become regional, or become generalised, with anaphylactic symptoms such as urticaria, flushing and angioedema, as well as more serious respiratory and cardiovascular symptoms. The reactions can be fatal. Immediate and delayed reactions are seen (51-54), delayed ones being less common (53). Anaphylactic reactions to Hymenoptera stings are not dose-dependent or related to the number of stings (3, 15, 33). Most deaths related to Hymenoptera stings are the result of immediate hypersensitivity reactions that result in anaphylaxis. However, massive envenomations can cause death in non-allergic individuals. The lethal dose has been estimated to be approximately 20 stings/kg in most mammals (2).

Systemic allergic reactions to Hymenoptera venom in general have been estimated to occur in 0.4 to 3.3% of a population. Epidemiological studies indicate that from 15 to 25% of the general population can be sensitised to different Hymenoptera venoms. The degree of exposure may be related to the different prevalences found in those studies (55). Older United States studies suggested that deaths from Polistes stings were more common than those from Vespula or Dolichovespula (56-57). The European experience is different, with Honey bee and Vespula deaths more common (3).

However, the prevalence of hypersensitivity to Polistes is unclear: in some local European studies of Hymenoptera stings, the term Wasp was mentioned but no specific details were given about the species involved (58). This adds greatly to the confusion about the role of different vespids in sting events. For example, in Spanish studies up to the 1990’s, both P. gallicus and P. dominulus were grouped together as P. gallicus (59). In other studies, such as a report from Turkey, V. vulgaris was the only vespid studied, although other species are present in that country (4, 60).

Nonetheless, some guidance and information can be gleaned from a number of other published studies. Importantly, regional differences may occur due to a number of factors relating to the insects’ distribution and interaction with human activities (such as Bee keeping). Methods of detecting sensitisation also vary widely. In the central, northern and eastern parts of Europe, Vespula, Vespa and Bee stings are more prevalent, whereas in the Mediterranean areas, Polistes and Vespula stings are more frequent, as mentioned above (4). Furthermore, since the cross-reactivity between European and American Polistes is only partial, with significant differences in specificities, studies may not be extrapolated between the pair; this has been confirmed in in vitro and in vivo studies (6, 15, 25, 29, 33). Indeed, in a study of 4 Polistes-allergic individuals in whom skin-specific IgE negative to the American Polistes, all were positive to European Polistes venoms; 2 had  experienced severe reactions (15). The authors concluded that there is no correlation between skin test reactivity and severity of the reaction. (See Paper wasp/Common paper wasp (Polistes exclamans) i4 for an overview of American Polistes.)

An Italian study aimed at evaluating the prevalence of cutaneous sensitivity to Hymenoptera venoms in 1175 primary school children, 19.40% were found to have a history of Hymenoptera sting reactions, of whom 19.06% had experienced local reactions and 0.34% (4) local and systemic reactions. Most subjects were shown to have skin-specific IgE to Honey bee venom (2.98%). Skin-specific IgE for Wasp was documented in 1.45%, and only 12 subjects (1.02%) had skin-specific IgE for Polistes venom (61).

A number of Spanish studies evaluated the importance of Polistes sensitisation in that population. In a study of 27 patients who had experienced allergic reactions to vespid stings, the authors concluded that in southern Spain, sensitisation to P. gallicus was more prevalent than to V. germanica (44% vs. 33%). However, there was a considerable (but not complete) degree of cross-reactivity between the 2 species. The authors concluded that in spite of Polistes being an important species in Spain and other Mediterranean countries, V. germanica venom was used almost exclusively for diagnosis and immunotherapy; this suggests that diagnosis has been incomplete (62). In a study that analysed the clinical features and the severity of systemic reactions to Wasp stings, 115 patients who had experienced an anaphylactic reaction to Wasp sting and had specific IgE for venoms from Vespula and/or Polistes were evaluated. Cutaneous symptoms had been experienced by 90.4%, respiratory by 54.8%, cardiovascular by 33.9%, and gastrointestinal in 21.7%. Reactions were mild in 40.8% and severe in 59.1%. The mean age of patients without cutaneous symptoms was higher. Cardiovascular involvement was more frequent in males (63). In a rural study of the prevalence of insect sting allergy and sensitisation to the venom of P. dominulus, Vespula germanica and Honey bee, systemic reactions were documented in 2.3% (of which 57.6% were shown to have specific IgE directed at the causative venom). Large local reactions were found in 26.4% (of which only 28.5% had specific IgE for the causative venom). Asymptomatic sensitisation (positive RAST) was observed in 16.4% of the subjects without reactions. The authors concluded that the prevalence of systemic sting reactions in this rural community was higher than in other general populations in the same Mediterranean region, but similar to that in other rural populations studied (55).

In a Spanish study that investigated the presence of specific IgE to P. dominulus, Vespula germanica and Vespa crabro in sera of patients sensitised to vespids, serum-specific IgE showed that although the majority of patients had IgE antibodies to all 3, there was a marked predominance of antibodies to P. dominulus. These findings were related to the distribution of the insect in the areas where the sera were obtained. When the region examined was divided into 3 zones according to geographical and insect distribution differences, serum-specific IgE evaluation indicated that although sensitisation to P. dominulus predominated over sensitisation to Vespula germanica and the latter over sensitisation to Vespa crabro, there were significant differences in the prevalence of sensitisation to each vespid in each of the regions studied. Importantly, the further evaluation of serum-specific IgE indicated that in most instances patients were originally sensitised to a single vespid and were serum-specific IgE positive to the other venoms due to cross-reactivity. Only in a minority of cases were coexisting antibodies to 2 insects present (35).

The purpose of another Spanish study was to describe the clinical and epidemiological features of anaphylactic reactions to Hymenoptera stings, with a case-history analysis according to severity. A hundred and thirteen patients with a mean age of 40.1 were included. Adverse reactions occurred to Bee venom in 10.6% of patients and to Wasp venom in 89.4%. Specific IgE was positive to Vespula in 91.9% of subjects, to Polistes in 71.4%, and to Bee in 28.7%. Sensitisation to both Vespula and Polistes was found in 50.4%. Among 106 patients, local large reactions were reported by 35.9% and systemic reactions by 16.5%. The most common symptoms were pruritus (77.8%), hives (57.5%), oedema (54.8%), erythema (52.2%), dizziness (51.3%) and dyspnoea (49.5%). Severe reactions occurred in 65.5% of patients (64). In an observational, prospective and cross-sectional study carried out on a sample of 1064 in a total working population of 7887 Spanish subjects, 7.6% were hypersensitive to Hymenoptera. Local severe reactions were reported by 5.3% and systemic reactions by 2.3%. Age, sex, and atopy had no influence. Sensitisation to Polistes was more frequent than to Vespula (65).

In a French study of the influence of desensitisation on venom-allergic patients, 200 patients aged 4 to 82 who had experienced systemic reactions were recruited. It was inferred that they showed an average prevalence of sensitisation, with 72 being allergic to Honey bee venom, 83 to Yellow jacket venom, and 45 to both Yellow jacket and Polistes venom (66). Hymenoptera-sensitive allergic subjects in Marseille were studied in order to determine the serum-specific IgE to venoms from P. dominulus, Vespula germanica, and Vespa crabro. All the sera studied had IgE antibodies to at least 1 of the venoms tested, and 50% had IgE antibodies that reacted with more than 1 venom (67).

A stratified random sample of 480 Greek subjects, aged 20-60, was tested for reactions to Honey bee, Paper wasp, and Common wasp, and it was reported that the prevalence of venom sensitisation, as determined by skin-specific IgE determination, was 32.7%. Sensitisation appears to be more common in rural areas. The prevalence of systemic reactions was 3.1%, of which 86.7% were documented to have skin-specific IgE. Large local reactions were reported by 4.6% of the subjects (skin-specific IgE demonstrated in 77.3%). Asymptomatic sensitisation (positive skin-specific IgE) was found in 28.7% of subjects with no history of an allergic sting reaction (68).

Polistes sensitisation decreases but is still present even in colder northern countries.

A study of 1399 men and women, aged 20 to 44 and resident in 3 areas of Sweden, investigated the prevalence of sensitisation to the venom allergens of Honey bee and Wasps, as assessed by serum-specific IgE determination. It was found that 9.3% had specific IgE for Bee or Wasp venom. Systemic reactions to Bee or Wasp stings were reported by 1.5%, and 0.6% had both. The study concluded that the prevalence of Hymenoptera allergy was rather low when compared with the prevalence in other countries (69).

In Iceland, the Vespidae species were first seen in 1973 and since then have inhabited the island in ever-increasing numbers. The first proven case of sensitisation and anaphylaxis to Hymenoptera was reported in 2003 (70).

Epileptic attacks have been attributed to Wasp stings. In a patient who had experienced 2 epileptic attacks, each one associated with anaphylaxis due to Wasp venom, and in whom serum-specific IgE against Polistes species venom was raised, it was considered likely that the attacks were due to anoxia secondary to hypotension caused by vasodilatation and cardiac involvement in anaphylaxis (71).

A patient was reported who had urticaria pigmentosa and anaphylactic shock due to a vespid sting and was monosensitive to P. dominulus venom. The authors emphasise the importance of recognising the differences between American and European Polistes and state that in this case, omitting to perform specific IgE evaluation for P. dominulus venom would have led to a misdiagnosis of the anaphylaxis as non-IgE-mediated (72).

Interestingly, even beekeepers may be sensitised to Polistes and not Honey bee only. In 246 Canary Island beekeepers, 128 had experienced an adverse reaction to Hymenoptera greater than merely a local reaction. Serum-specific IgE for Apis mellifera was positive in 126, for Vespula in 27 and for Polistes in 9 (73).
 
Other reactions
Electrographic changes after insect stings have been reported both with and without systemic symptoms. A patient is described who developed paroxysmal atrial fibrillation after receiving venom and pollen immunotherapy. The patient was found to be in atrial fibrillation and to have systemic symptoms immediately after administration of immunotherapy. After an injection of epinephrine, the patient converted back to a normal sinus rhythm and the systemic symptoms resolved (74).

Although unusual, delayed clinical reactions to Hymenoptera stings have been reported: they can affect organs or systems generally not involved in the immediate hypersensitivity reaction. A 51-year-old man was reported as having presented with immediate, strong local and systemic allergic reactions after 2 stings of Paper wasps; the second set of reactions was triggered by a string that occurred after the third venom immunotherapy injection. He quickly improved after intravenous methylprednisolone administration, but developed acute polyradiculoneuropathy with muscle weakness, paresthesia and difficulties in standing up and walking approximately 40 hours later. Skin and specific IgE tests showed sensitisation to Paper wasp. Based on laboratory findings, the authors suggested that the mechanism may have been a delayed immunological response to Wasp antigens, followed by an allergy-triggered autoimmune reaction (75).
 
Compiled by Dr Harris Steinman, harris@zingsolutions.com

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