Date Published: July 7, 2017
Publisher: Public Library of Science
Author(s): Eleonora Savi, Cristoforo Incorvaia, Elisa Boni, Marina Mauro, Silvia Peveri, Valerio Pravettoni, Oliviero Quercia, Federico Reccardini, Marcello Montagni, Laura Pessina, Erminia Ridolo, Menno C van Zelm.
Venom immunotherapy (VIT) is highly effective in preventing allergic reactions to insect stings, but the appropriate venom must be used to achieve clinical protection. In patients with multiple positive results to venoms, molecular allergy diagnostics or CAP-inhibition may identify the causative venom. Concerning allergy to venom from Polistes spp. it has been proposed that only the European species P. dominulus should be used for VIT. However, this recommendation is not present in any international guideline. Using both laboratory and clinical data, we aimed to evaluate the reliability of this proposal.
We performed an in vitro study using CAP-inhibition to determine sensitization of 19 patients allergic to Polistes venom. The clinical study included 191 patients with positive tests to Polistes treated with VIT, 102 were treated with P. dominulus and 89 were treated with a mix of American Polistes (mAP).
The difference in % of inhibition was significant concerning inhibition of P. dominulus sIgE by P. dominulus venom (79.8%) compared with inhibition by mAP venom (64.2%) and not significant concerning the inhibition of mAP sIgE by P. dominulus venom (80.1%) and by mAP venom (73.6%). Instead, the clinical protection from stings was not statistically different between the two kinds of venom.
The data from CAP inhibition would suggest that the choice of either P. dominulus venom or mAP venom for VIT is appropriate in patients with CAP inhibition higher than 70%, but the clinical data show the same odds of protection from stings using for VIT P. dominulus or mAP venom.
Venom immunotherapy (VIT) is an effective treatment for preventing anaphylactic reactions to Hymenoptera stings [1–3]. The choice of venom to be used for VIT is of obvious importance in warranting the clinical protection from the stings of the culprit insect. This is particularly true for patients with multiple positive results to diagnostic tests with venoms and especially for patients allergic to vespids . Because IgE responses to cross-reacting allergens cause positive results to all venoms, comparing the sensitivity of tests to different venoms does not resolve the issue. Previously, it was common to prescribe VIT for all venoms eliciting a positive response, but in recent years, in vitro techniques that can identify the causative venom have been introduced. The first method was RAST-inhibition, by which Hamilton et al. demonstrated that one third of 305 patients with allergic reactions to stings and who tested positive for Vespula- and Polistes- IgE in the skin and/or serum were identified as candidates for exclusion of Polistes from immunotherapy because their anti-Polistes IgE was more than 95% cross-inhibitable with Vespula venom . Over the previous decade, molecular allergy techniques have a further advanced, enabling measurement of IgE specific to single venom allergen molecules, thus distinguishing simple cross-reacting components from causative molecules . Three studies showed that by measuring sera from patients with double positivity to Vespula and Polistes specific IgE to major allergens such as Ves v 1 and Ves v 5 from Vespula species and Pol d 1 and Pol d 5 from Polistes species, the responsible vespid was identified [7, 8, 9]. In addition, a particular issue was raised in Europe concerning cross-reactivity between the European and the American species. European species, particularly those in Italy, include P. gallicus, P. dominulus, P. nymphus, P. biglumis, P. associus, P. sulcifer, P. semenowi, and P. atrimandibularis; P. gallicus and P. dominulus are the most medically important. American species include P. annularis, P. fuscatus, P. metricus, P. apaches and P. exclamans. Cross-reactions among venoms from different Polistes spp. are quite extensive . However, in a an evalutation of 21 Italian patients with reactions to Polistes stings as determined using skin tests, RAST and RAST inhibition (on only 10 patients), Severino et al. reported that RAST inhibition demonstrated only partial cross-reactivity between American and European species and that P. dominulus, and P. gallicus, have exclusive allergens, thus suggesting that such venoms are more suitable than the American mix in Italian patients . However, no other investigations have since been reported. Therefore, we compared venom from P. dominulus and from the mix of American Polistes (mAP) using in vitro CAP-inhibition for diagnosis and retrospectively evaluated the rate of clinical protection from subsequent stings in a group of Italian patients with allergic reactions to Polistes venom previously treated with P. dominulus or mAP, respectively.
The rationale of the in vitro study was to assess the relative importance of allergens from P. dominulus and mAP by measuring their cross-inhibition. Table 1 reports the results of CAP inhibition in individual patients. The mean value of sIgE to P. dominulus before inhibition was 9.85 ± 8.76 kU/L. After inhibition with P. dominulus and mAP the values decreased to 1.86 ± 2.08 and 2.80 ± 2.72 kU/L, respectively. The mean value of sIgE to mAP before inhibition was 6.90 ± 7.71 kU/L. After inhibition with mAP and P. dominulus the values decreased to 1.45 ± 1.60 and 1.35 ± 1.76, respectively. The difference in % of inhibition was significant (p = 0.003) concerning inhibition of P. dominulus sIgE by P. dominulus venom (mean% of inhibiton: 79.8%) compared with inhibition by mAP venom (mean % of inhibiton: 64.2%) and not significant concerning the inhibition of mAP sIgE by P.dominulus venom (mean % of inhibiton: 80.1%) and by mAP venom (mean % of inhibiton: 73.6%). (S1 Fig).
Hymenoptera belonging to Polistes spp have a worldwide distribution, with variable presence in different areas. In America the most common species are P. annularis, P. apachus, P. exclamans, P. fuscatus, and P. metricus, while in Europe P. gallicus and P. dominulus prevail. In particular, P. dominulus is the dominant species in Southern Europe . However, the entomological importance of Polistes spp. must be distinguished from the allergological importance. Extensive cross-reactivity is known to occur for Polistes allergens, including the species-specific antigen 5, wish shows an 85% identity the European species P. gallicus and the American species P. annularis . Furthermore, a consensus documents lack a recommendation to use exclusively P. dominulus venom for VIT in Polistes allergic patients in Europe.