Phospholipase A1-based cross-reactivity among venoms of clinically relevant Hymenoptera from Neotropical and temperate regions

Abstract

Molecular cross-reactivity caused by allergen homology or cross-reactive carbohydrate determinants (CCDs) is a major challenge for diagnosis and immunotherapy of insect venom allergy. Venom phospholipases A1 (PLA1s) are classical, mostly non-glycosylated wasp and ant allergens that provide diagnostic benefit for differentiation of genuine sensitizations from cross-reactivity. As CCD-free molecules, venom PLA1s are not causative for CCD-based cross-reactivity. Little is known however about the protein-based cross-reactivity of PLA1 within vespid species. Here, we address PLA1-based cross-reactivity among ten clinically relevant Hymenoptera venoms from Neotropical and temperate regions including Polybia paulista (paulistinha) venom and Vespula vulgaris (yellow jacket) venom. In order to evaluate cross-reactivity, sera of mice sensitized with recombinant PLA1 (rPoly p 1) from P. paulista wasp venom were used. Pronounced IgE and IgG based cross-reactivity was detected for wasp venoms regardless the geographical region of origin. The cross-reactivity correlated well with the identity of the primary sequence and 3-D models of PLA1 proteins. In contrast, these mice sera showed no reaction with honeybee (HBV) and fire ant venom. Furthermore, sera from patients monosensitized to HBV and fire ants did not recognize the rPoly p 1 in immunoblotting. Our findings reveal the presence of conserved epitopes in the PLA1s from several clinically relevant wasps as major cause of PLA1-based in vitro cross-reactivity. These findings emphasize the limitations but also the potential of PLA1-based HVA diagnostics.

Current challenges in molecular diagnostics of insect venom allergy

“…This approach may be also applied for the identification of Vespula and Polistes venom sensitization. Recently, we showed significant variations in the levels of peptide-based cross-reactivity among PLA1 from Vespinae venoms, even in members of the same genera (Polistinae) [36]. Levels of sIgE against the primary sensitizer were significantly higher.…”

“…A recent study showed significant levels of peptide-based cross-reactivity between antigen 5 from several members of Vespinae and Polistinae [27]. Venom PLA1 were shown to cross-react to a lesser extent [10,36].…”

“…Epidemiologic surveys as well as studies for the evaluation of the diagnostic systems currently applied are scarce. Standardized venom preparations or individual allergens derived from the venom of the major allergy elicitors Polybia paulista, Apoica pallens, and fire ants are not available [36,56]. Routine diagnostic tests in Brazil are based on manufactured crude venom extracts thus increasing the incidence of cross-reactivity and therefore causing diagnostic failure to detect the culprit insect.…”

Hymenoptera Venom Allergy: Management of Children and Adults in Clinical Practice

“…In Southern Europe, double Vespula-Polistes sensitization is more frequent than Apis-Vespula sensitization [112], and cross-reactivity between allergens of 2 species often poses diagnostic difficulties [113,114]. In cases of difficult interpretation between sensitization Vespula and sensitization to Polistes, the use of Ves v 5 and Pol d 5 seems to be helpful in clinical practice, provided that the difference in specific IgE levels between the 2 molecules is particularly significant, with at least double values of one recombinant over the other [114][115][116].…”

Evaluation of Inter and Intraspecific Differences in the Venom Chemical Compositions of Polybia paulista Wasps and Ectatomma brunneum Ants Using FTIR-PAS

“…Although there is a significant number of studies with the venom of P. paulista (Souza et al, 2009;Santo et al, 2011;Pinto et al, 2012;Hoshina et al, 2013;Jacomini et al, 2013;Gomes et al, 2014;Dias et al, 2014Dias et al, , 2015Leite et al, 2015;Vinhote et al, 2017;Perez-Riverol et al, 2018) and some with the venom of E. brunneum (Pluzhnikov et al, 2014;Touchard et al, 2015;Aili et al, 2016) only a few of them investigated intraspecific differences in venom compositions, for example, P. paulista (Mendonça et al, 2017) and E.brunneum Bernardi et al (2017). As the occurrence of these two species is ample, they end up being good study models to evaluate intraspecific differences of their venoms.…”