Our global life sciences company brings diagnostic testing & drug development together.

Hymenoptera Venom Allergy (HVA) with Components Profile

CPT: 83520; 86003(x3); 86008(x8)
To be determined. Updates will be made when available.
83520; 86003(x3); 86008(x8)
Updated on 11/22/2021

Test Includes

Honey Bee Venom (HBV) IgE plus IgE to HBV components Api m 1, Api m 2, Api m 3, Api m 5, & Api m 10; Yellow Jacket Venom (YJV) IgE plus IgE to YJV components Ves v 1 & Ves v 5; Paper Wasp Venom (PWV) IgE plus IgE to PWV component Pol d 5; Tryptase.

Reflex criteria: If any of the following are true, Cross-reactive Carbohydrate Determinant (CCD) IgE is performed: Honey Bee Venom (HBV) IgE ≥0.10 kU/L and all HBV components negative (<0.10 kU/L); Yellow Jacket Venom (YJV) IgE ≥0.10 kU/L and all YJV components negative (<0.10 kU/L); Paper Wasp Venom (PWV) IgE ≥0.10 kU/L and PWV component Pol d 5 negative (<0.10kU/L)

Expected Turnaround Time

3 - 5 days

Related Documents

Specimen Requirements




2 mL

Minimum Volume

1.0 mL (Note: This volume does not allow for repeat testing.)


Gel-barrier tube

Storage Instructions

Room temperature

Stability Requirements



Room temperature

14 days


14 days


3 months

Freeze/thaw cycles

Stable x3

Test Details


Support the diagnosis of hymenoptera venom allergy (HVA) by detection of sIgE antibodies to whole venom extracts and individual allergenic venom proteins. Identifying sIgE responses to specific molecular targets with component resolved diagnostics (CRD) helps fine-tune the diagnosis by distinguishing species-specific, co-reactive, or cross-reactive sensitizations. An accurate diagnosis, in turn, facilitates treatment, including prescription of venom immunotherapy.1


The high rate of asymptomatic sensitization to hymenoptera venom makes an accurate diagnosis of Hymenoptera venom allergy challenging.2,3,15,17

There is no correlation between the severity of sting reactions and the concentration of venom sIgE to whole venom extracts.4-7,19 or individual components,71 and some patients with minimal level or absent specific IgE to these entities can develop severe anaphylaxis.

An increase in serum specific IgE levels after a sting is not an indicator for conversion into a clinically relevant hypersensitivity in patients with no history of severe systemic reaction to hymenoptera sting.17

sIgE to CCDs does not exclude clinical relevant sensitization to different venoms.11

Negative allergy test results can occur in patients with convincing history of sting-induced systemic reactions due to a number of causes including:

1. Testing performed in the refractory period following the sting reaction;

2. Loss of sensitization over time;

3. Sensitizing allergen component(s) under-represented in diagnostic test reagent;

4. The presence of systemic mastocytosis, as negative results occur in up to 15% of these patients.8


Thermo Fisher ImmunoCAP® Allergen-specific IgE

Additional Information

Hymenoptera venom allergy (HVA) is a potentially life-threatening allergic reaction that occurs following a honeybee, vespid, or ant sting. Most hymenoptera stings produce a transient local reaction that can last up to several days and generally resolves without treatment. More marked swelling extending from the sting site can occur in sensitized individuals as the result of an IgE-mediated late-phase reaction.9 Systemic reactions to the venoms of stinging Hymenoptera may be restricted to generalized symptoms of the skin, but can also affect the respiratory and vascular system and lead to multi-organ failure. Fatal anaphylaxis after Hymenoptera stings is a rare but well-recognized cause of sudden death.10-12 The risk of a future systemic reaction on hymenoptera sting is significantly increased in patients who have historically experienced large local reactions after a sting.13

Identification of the species of insect responsible for the sting reaction is useful in establishing the diagnosis, prescribing treatment, and educating patients in avoidance measures. The most prevalent hymenoptera causing allergic reactions in the US belong to the Apidae and Vespidae families.14-16 The Apidae family includes the subfamilies Apinae (honeybees; Apis mellifera) and Bombinae (bumblebees; Bombus terrestris), while the Vespidae family is composed of the Vespinae subfamily, including the genera Vespula (yellow jacket; Vespula vulgaris), and the Polistinae subfamily, which includes the genus Polistes (paper wasp; Polistes dominula).

The diagnosis of HVA is based on the clinical history of a systemic/anaphylactic sting reaction and the detection of IgE sensitization to relevant insect venoms.9,15 Patient work-ups have historically included tests using whole venom preparations, either “in vivo” via skin testing or “in vitro” by measuring serum levels of venom specific IgE (sIgE) antibody.11 Specific IgE antibodies are produced after the very first sensitizing event and can be detected immediately after the first allergic reaction, although it is recommended to perform the testing 1-4 weeks after the last sting.12 A clear documented history of a sting-associated reaction is a prerequisite to a patient work-up for HVA because many patients express positive test results without a history of clinically significant sting-associated symptoms.17,18 Venom-specific immunotherapy (VIT) is currently the only known curative therapy, but its efficacy greatly depends on the correct identification of the culprit insect species.19-22

Hymenoptera venoms contain complex mixtures of glycosylated and non-glycosylated proteins and peptides.23,24 While the venom from each species of hymenoptera is unique, the various venoms contain multiple homologous protein components. One of the main obstacles to identification of the correct allergy-eliciting insect is immunological cross reactivity, due to the significant redundancy of the amino acid sequences of their allergenic proteins. Differentiation between primary sensitization and cross-reactivity-driven responses using whole venom extract based tests can be challenging, especially in the cases where tests with multiple extracts are positive.11,15 Dual positivity complicates the process of selecting the appropriate venom for immunotherapy in cases where the culprit insect is unknown.15 As many as half of HVA allergic patients have positive results for both honeybee venom (HBV) and yellow jacket venom (YJV) using whole venom extract-based diagnostic tests.12,15,18,25,26,27 Dual positivity for YJV and paper wasp venom (PWV)is even more common.12,15,18,23,25,26 While some duel positive patients may have been stung by multiple types of hymenoptera engendering multiple primary sensitizations, a single, primary sensitizer is a more common cause of HVA.

Component Resolved Diagnostics (CRD) refers to the use of individual, purified, or recombinant, allergens for in vitro detection of allergen sIgE.11,12,15,21,28,29,32 CRD can be used to discriminate between primary sensitization and cross-reactivity in patients with double-positive results by whole venom-based diagnostic tests.12 Some allergen components present in a given whole venom preparation are unique to that venom and not present in other potential venom sensitizers. These species-specific components are referred to as “marker allergens” as they serve as a marker of genuine sensitization to a specific venom source.15 Thus, CRD can often distinguish true dual- from single-species sensitization.11,15,28,30,31 CRD can also be valuable in patients with a proven history of a venom-induced systemic reaction but negative whole venom extract-based allergy tests, as it allows for the detection of sensitization to potent individual venom allergens that are underrepresented in whole venom extracts.11,12,15,21,28,32,33 Studies have also found a correlation between the pattern of CRD sensitization and VIT efficacy,34,35 as well as VIT side effects.36

HBV: Honeybee (Apis mellifera) Venom

HBV is the best characterized of the hymenoptera venoms due to the prominence of beekeeping and the associated high prevalence of allergic reactions associated with honeybee stings.37,38 The venom allergens of different honeybee species are similar and are reported to be highly cross-reactive.11 Twelve key proteins designated Api m 1-12 are currently included in the official allergen nomenclature database (,39 Among them, Api m 1, Api m 2, Api m 3, Api m 5 and Api m 10 are referred to as major allergens in that more than 50% of confirmed honeybee-sensitized patients show IgE reactivity to these components.40,41 The combined testing for sIgE to these five HBV components has a diagnostic sensitivity of approximately 95% for identifying HBV-allergic patients.21,40 Of these five HBV components, three (Api m 1, Api m 3, and Api m 10) are unique to the Apidae family and not present in the venom of yellow jacket or other Vespidae,15,24 and thus serve as a markers of primary HBV sensitization. In contrast, Api m 2 and Api m 5 are cross-reactive with venom proteins of hymenoptera of the Vespidae family.15,24

Api m 1, referred to as phospholipase A2, is a neurotoxin that effects the peripheral neuromuscular system.24 The prevalence of Api m 1 sensitization is reported to range between 57% and 97% among HBV-allergic patients.27,33,34,40,42-46,54 While detection of Api m 1 sIgE indicates likely primary HBV sensitization, a lack of sensitization to Api m 1 in patients suspected of having HBV allergy is insufficient to rule out genuine HBV sensitization.15

Api m 2 is an enzyme that breaks down hyaluronic acid, a polysaccharide of high molecular mass that maintains cell adhesion.47 This facilitates toxin diffusion beyond the site of the sting.24,47 Api m 2 is structurally similar to the Ves v 2, a hyaluronidase from yellow jacket venom (YJV),48,50,51 and thus positive Api m 2 sIgE results can occur as the result of exposure either to HBV to YJV.15 Ves v 2 represents only a minor allergen of YJV, while Api m 2 is an important major allergen of HBV.34,40,49,51 Assessment of sensitization to venom marker components (from both HBV and YJV) is required to ascertain the primary sensitizer responsible for Api m 2 sIgE positivity.11,15

Api m 3 is a marker allergen for primary HBV sensitization since it is not found in the venoms of other hymenoptera. Api m 3 is present in relatively low concentration in HBV and is poorly represented in several of the licensed preparations routinely used for honeybee venom immunotherapy and diagnostics, so Api m 3 can be positive in whole venom extract test-negative patients.11,50,54

Api m 5 is a dipeptidyl peptidase and plays important role in venom toxicity by activating proteins by cleaving amino acids from their n-terminals. Api m 5 is structurally similar to dipeptidyl peptidase proteins from other hymenoptera, including Ves v 3 from YJV50,51 and a dipeptidyl peptidase from Polistes dominula venom.52 Due to high inter-species cross-reactivity, positive Api m 5 results are not specific for HBV exposure as they can reflect sensitization to other hymenoptera venom.15

Api m 10 is a complex protein that is also referred to as icarapin.15,34,53-56 It is an unstable protein of unknown function that has homologs in other insect species.56 This HBV marker allergen is present in relatively low abundance in HBV and is poorly represented or missing in several of the licensed preparations routinely used for honeybee venom immunotherapy. A retrospective multi-center study found that a predominant sensitization to Api m 10 represents a relevant risk factor for treatment failure of VIT,54 ostensibly due to its low relative concentration in certain immunotherapy extracts.54,57

YJV: Yellow Jacket (Vespinae Vespula) Venom

Yellow jacket is the common American name for predatory social wasps of the genera vespula, dolichovespula and vespa.11,58 Members of these genera are known simply as "wasps" in other English-speaking countries. YJV proteins from the various species are closely related21,25 and include the prominent allergens Ves v 1 and Ves v 5.59-61 Ves v 1 and Ves v 5 are marker allergens, and the presence of serum sIgE to these proteins indicates primary yellow jacket sensitization.15

Ves v 1, also referred to as phospholipase A1, is responsible for the hydrolysis of the plasma membrane phospholipids, allowing the diffusion of toxins into adjacent cells and producing edema.47 The prevalence of Ves v 1 sensitization in YJV-allergic patients is reported to range between 33% and 79%.9,11,12,41,62-65

Ves v 5 is the “Antigen 5” protein from vespids.61 Antigen 5 proteins are recognized as the major and most potent allergen in venoms of the Vespidae family and are found in the venom of all Vespidae species, including YJV. The biological function of these proteins is as of yet unknown. Antigen 5 proteins are not found in HBV. Antigen 5 proteins are related by high amino acid sequence identity to pathogenesis-related proteins from mammals, reptiles, insects, fungi, and plants.66 Homologous Antigen 5's from a large number of different yellow jackets, hornets, and paper wasps are known and patients show varying extents of cross-reactivity to these proteins.47,66 Sensitization rates to Ves v 5 in YJV-allergic patients are reported to range between 85% and 98%.27,41,51,62-64,67,68

Testing for sIgE to both Ves v 1 and Ves v 5 results in a diagnostic sensitivity as high as 92% to 98% for the detection of YJV allergic patients.27,28,42,43,46,48,51,63,64,69-71 Patients that test negative for sIgE to both Ves v 1 and Ves v 5 are very unlikely to have been sensitized by YJV exposure.11,12,18

PWV: Paper Wasp (Polistes dominula) Venom

Polistes dominula is an invasive species that originated in Europe and is now found in the northeastern United States as well as in Europe and Australia. The related species Polistes exclamans, Polistes annularis, and Polistes fuscatus are indigenous to North America.11,58 There are no marker allergens specific to Polistes, and patients primarily sensitized to PWV are often misdiagnosed as YJV allergic and at risk for being inadequately protected by yellow jacket VIT.15,72

Pol d 5 is the “Antigen 5” protein from Polistes dominula and exhibits significant cross-reactivity with Ves v 5 of YJV. Antigen 5 proteins from Vespula and Polistes have sequence identity of approximately 57%.47,73

Cross-reactive Carbohydrate Determinants (CCDs)

One of the main obstacles to determining the species responsible for HVA in a given individual using whole venom extract-based diagnostics is the occurrence of specific N-linked glycosylation of some Hymenoptera venom allergens. Many relevant venom allergen proteins are post-translationally glycosylated with unique alpha 1,3-linked fucose residues.15 While many mammalian proteins are glycosylated, only plants and insect proteins contain this specific glycan residue. Since this specific glycosylation does not occur in humans, exposure to proteins that are glycosylated with alpha 1,3-linked fucose residues often induces allergic sensitization and IgE production. This glycan sIgE does not reflect exposure to any specific allergen but represents a pan-sensitization to “Cross-reactive Carbohydrate Determinants” or “CCD” sensitization.15 IgE antibodies directed against CCD confound diagnostic tests using whole venom extracts.11 CCD-IgE produces positive test results using multiple venom extracts that doesn’t reflect specific venom exposure.11 CCD-sIgE accounts for up to 50% of double positivity to HBV and YJV.72 Glycosylation with CCD sugars does not occur in the manufacture of recombinant allergen components. As a consequence, tests using component proteins can be used to differentiate true venom sensitization from CCD sensitization in venom-extract positive patients.9,11,15,48,69,75 Unlike YJV and HBV, the venom of Polistes species are devoid of any a 1,3-core-fucosylation and hence are not confounded by CCD interference.76

The measurement of CCD-specific IgE can be of value in cases where venom component testing is not definitive, especially where a venom extract IgE is positive but all venom components for that species is negative.21,28

Resolving Double Positivity

Positivity to more than one venom extract can occur due to:

- True double-sensitization to multiple species of hymenoptera;

- Sensitization to cross-reacting allergen proteins present in venoms of different species;

- Sensitization to CCD (carbohydrate determinants) present in venoms of different species.

CRD can help resolve the cause of double positivity.

Apidae vs Vespula. It has been demonstrated that the use of Api m 1 on its own is insufficient to detect all HBV allergic individuals and therefore to distinguish between primary bee and wasp venom sensitization.46,77 The use of other HBV marker allergens Api m 3 and Api m 10 and YJV marker allergens Ves v 1 and rVes v 5 improves the accuracy of determination of primary allergen sensitization.19,45,46,54,62

Vespula vs Polistes. The discrimination between Vespula spp. and Polistes spp. sensitization is challenging due to high phylogenetic overlap between the two species.12,24,61,73 Measurement of Ves v 5 and Pol d 5 can suggest the primary sensitizer in cases where the difference in specific IgE levels between the two molecules is particularly significant, with at least double values of one recombinant over the other.70,78-80 However, a recent study showed that such proposed ratio was less accurate than CAP-inhibition results.81

Venom Allergy in patients with Mast Cell Disease

Patients suffering from mastocytosis and/or elevated baseline serum tryptase are more likely than others to go into anaphylaxis when experiencing an insect sting.8,9,15,31,38,63,82-84 The Stinging Insect Hypersensitivity Practice Parameter Update 2016 workgroup has recommended that venom allergy testing is appropriate in patients with indolent systemic mastocytosis, even with no history of allergic reaction to a sting, and that the clinician should consider the possibility of testing (and treating) such patients.9 Patients with mastocytosis frequently have negative allergy test results despite a clear history of hymenoptera sting-induced systemic allergic reaction.8,9,15,31,85 Basal serum tryptase should be measured when there is a history of severe insect sting anaphylaxis (especially with hypotension or the absence of urticaria) and when skin and serum test results for venom-specific IgE are negative.9,86 Adult patients with mastocytosis and/or elevated baseline serum tryptase are at risk for more severe reactions following stings.11,87


1. Sturm GJ, Arzt-Gradwohl L, Varga EM. Medical Algorithms: Diagnosis and treatment of Hymenoptera venom allergy. Allergy. 2019 Oct;74(10):2016-2018.30912798
2. Bilò MB, Bonifazi F. The natural history and epidemiology of insect venom allergy: clinical implications. Clin Exp Allergy. 2009 Oct;39(10):1467-1476.19622088
3. Golden DB. New directions in diagnostic evaluation of insect allergy. Curr Opin Allergy Clin Immunol. 2014 Aug;14(4):334-339.24915545
4. Golden DB, Moffitt J, Nicklas RA, et al. Stinging insect hypersensitivity: a practice parameter update 2011. J Allergy Clin Immunol. 2011Apr;127(4):852-854.e1-e23.21458655
5. Krishna MT, Ewan PW, Diwakar L, et al. Diagnosis and management of hymenoptera venom allergy: British Society for Allergy and Clinical Immunology (BSACI) guidelines. Clin Exp Allergy. 2011 Sep;41(9):1201-1220.21848758
6. Sturm GJ, Heinemann A, Schuster C, et al. Influence of total IgE levels on the severity of sting reactions in Hymenoptera venom allergy. Allergy. 2007 Aug;62(8):884-889.17620065
7. Schäfer T, Przybilla B. IgE antibodies to Hymenoptera venoms in the serum are common in the general population and are related to indications of atopy. Allergy. 1996 Jun;51(6):372‐377.8837658
8. Alvarez-Twose I, Gonzalez de Olano D, Sanchez-Munoz L, et al. Clinical, biological, and molecular characteristics of clonal mast cell disorders presenting with systemic mast cell activation symptoms. J Allergy Clin Immunol. 2010 Jun;125:1269-1278.e2.20434205
9. Golden DB, Demain J, Freeman T, et al. Stinging insect hypersensitivity: A practice parameter update 2016. Ann Allergy Asthma Immunol. 2017 Jan;118(1):28-54.28007086
10. Schäfer T, Przybilla B. IgE antibodies to Hymenoptera venoms in the serum are common in the general population and are related to indications of atopy. Allergy. 1996 Jun;51:372-3778837658
11. Matricardi PM, Kleine-Tebbe J, Hoffmann HJ, et al. EAACI Molecular Allergology User’s Guide. Pediatr Allergy Immunol. 2016 May;27 Suppl 23:1-250.27288833
12. Bilò MB, Tontini C, Martini M, Corsi A, Agolini S, Antonicelli L. Clinical aspects of hymenoptera venom allergy and venom immunotherapy. Eur Ann Allergy Clin Immunol. 2019 Nov;51(6):244-258.31594296
13. Pucci S, D'Alò S, De Pasquale T, Illuminati I, Makri E, Incorvaia C. Risk of anaphylaxis in patients with large local reactions to hymenoptera stings: a retrospective and prospective study. Clin Mol Allergy. 2015 Nov 9;13:21.26557045
14 Park R. Hymenoptera Stings. Medscape website: Updated: Nov 8, 2018. Accessed May 2020.
15. Schiener M, Graessel A, Ollert M, Schmidt-Weber CB, Blank S. Allergen-specific immunotherapy of Hymenoptera venom allergy - also a matter of diagnosis. Hum Vaccin Immunother. 2017 Oct 3;13(10):2467‐2481.28604163
16. Jakob T, Rafei-Shamsabadi D, Spillner E, Müller S. Diagnostics in Hymenoptera venom allergy: current concepts and developments with special focus on molecular allergy diagnostics. Allergo J Int. 2017;26(3):93‐105.28503403
17. Sturm GJ, Kranzelbinder B, Schuster C, et al. Sensitization to Hymenoptera venoms is common, but systemic sting reactions are rare. J Allergy Clin Immunol. 2014 Jun;133(6):1635-1643.e1.24365141
18. Stoevesandt J, Hosp C, Kerstan A, Trautmann A. Sensitization to Hymenoptera venom marker allergens: prevalence, predisposing factors, and clinical implications. Clin Exp Allergy. 2018 Dec;48(12):1735-1743.30044028
19. Biló BM, Rueff F, Mosbech H, Bonifazi F, Oude-Elberink JN; EAACI Interest Group on Insect Venom Hypersensitivity. Diagnosis of Hymenoptera venom allergy. Allergy. 2005 Nov;60(11):1339-1349.16197464
20. Jakob T, Müller U, Helbling A, Spillner E. Component resolved diagnostics for hymenoptera venom allergy. Curr Opin Allergy Clin Immunol. 2017 Oct;17(5):363-372.28759475
21. Bilò MB, Ollert M, Blank S. The role of component-resolved diagnosis in Hymenoptera venom allergy. Curr Opin Allergy Clin Immunol. 2019 Dec;19(6):614-622.31343438
22. Sturm GJ, Arzt-Gradwohl L, Varga EM. Medical Algorithms: Diagnosis and treatment of Hymenoptera venom allergy. Allergy. 2019 Oct;74(10):2016-2018.30972798
23. Müller UR. Hymenoptera venom proteins and peptides for diagnosis and treatment of venom allergic patients. Inflamm Allergy Drug Targets. 2011 Oct;10(5):420‐428.21756243
24. Grosch J, Hilger C, Bilò MB, et al. Shedding Light on the Venom Proteomes of the Allergy-Relevant Hymenoptera Polistes dominula (European Paper Wasp) and Vespula spp. (Yellow Jacket). Toxins (Basel). 2020 May 14;12(5):323.34222898
25. Hemmer W. [Cross reactions between Hymenoptera venoms from different families, genera and species]. Hautarzt. 2014 Sep;65(9):775-779.25234625
26. Hemmer W, Focke M, Kolarich D, et al. 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 Dec;108(6):1045‐1052.11742287
27. Müller 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 Apim1 and Ves v5. Allergy. 2009 Apr;64(4):543-548.19120073
28. Blank S, Bilo MB, Ollert M. Component-resolved diagnostics to direct in venom immunotherapy: important steps towards precision medicine. Clin Exp Allergy. 2018 Apr;48(4):354-364.29331065
29. Golden DB, Kagey-Sobotka A, Norman PS, Hamilton RG, Lichtenstein LM. Insect sting allergy with negative venom skin test responses. J Allergy Clin Immunol. 2001 May;107(5):897-901.11344359
30. Eberlein B, Krischan L, Darsow U, Ollert M, Ring J. Double positivity to bee and wasp venom: improved diagnostic procedure by recombinant allergen-based IgE testing and basophil activation test including data about cross-reactive carbohydrate determinants. J Allergy Clin Immunol. 2012 Jul;130(1):155-161.22421265
31. Alfaya Arias T, Soriano Gómis V, Soto Mera T, et al. Key Issues in Hymenoptera Venom Allergy: An Update. J Investig Allergol Clin Immunol. 2017;27(1):19‐31.28211342
32. Sturm GJ, Jin C, Kranzelbinder B, et al. Inconsistent results of diagnostic tools hamper the differentiation between bee and vespid venom allergy. PLoS One. 2011;6(6):e20842.21698247
33. Sturm GJ, Hemmer W, Hawranek T, et al. Detection of IgE to recombinant Api m 1 and rVes v 5 is valuable but not sufficient to distinguish bee from wasp venom allergy. J Allergy Clin Immunol. 2011 Jul;128(1):247-248; author reply 248.21439627
34. Frick M, Fischer J, Helbling A, et al. Predominant Api m 10 sensitization as risk factor for treatment failure in honey bee venom immunotherapy. J Allergy Clin Immunol. 2016 Dec;138(6):1663-1671.27372568
35. Dalmau Duch G, Gazquez Garcia V, Gaig Jane P, Galán Nieto A, Monsalve Clemente RI. Importance of controlled sting challenge and component-resolved diagnosis in the success of venom immunotherapy. J Investig Allergol Clin Immunol. 2012;22(2):135-136.22533237
36. Ruiz B, Serrano P, Moreno C. IgE-Api m 4 is useful for identifying a particular phenotype of bee venom allergy. J Investig Allergol Clin Immunol. 2016;26(6):355-361.27996941
37. Spillner E, Blank S, Jakob T. Hymenoptera allergens: from venom to “venome.” Front Immunol. 2014 Feb 28;5:77.24616722
38. Ollert M, Blank S. Anaphylaxis to insect venom allergens: role of molecular diagnostics. Curr Allergy Asthma Rep. 2015 May;15(5):527.26139335
39. Radauer C, Nandy A, Ferreira F, et al. Update of the WHO/IUIS Allergen Nomenclature Database based on analysis of allergen sequences. Allergy. 2014 Apr;69(4):413-419.24738154
40. Köhler J, Blank S, Müller S, et al. Component resolution reveals additional major allergens in patients with honeybee venom allergy. J Allergy Clin Immunol. 2014 May;133(5):1383-1389.24440283
41. Cifuentes L, Vosseler S, Blank S, et al. Identification of Hymenoptera venom –allergic patients with negative specific IgE to venom extract by using recombinant allergens. J Allergy Clin Immunol. 2014;133:909-910.24290287
42. Hofmann SC, Pfender N, Weckesser S, Huss-Marp J, Jakob T. Added value of IgE detection to rApi m 1 and rVes v 5 in patients with Hymenoptera venom allergy. J Allergy Clin Immunol. 2011;127:265-267.20719373
43. Sturm GJ, Hemmer W, Hawranek T, et al. Detection of IgE to recombinant Api m 1 and r Ves v 5 is valuable but not sufficient to distinguish bee from wasp venom allergy. J Allergy Clin Immunol. 2011 Jul;128(1):247-248; author reply 248.21439627
44. Jakob T, Köhler J, Blank S, et al. Comparable IgE reactivity to natural and recombinant Api m 1 in cross-reactive carbohydrate determinant-negative patients with bee venom allergy. J Allergy Clin Immunol. 2012 Jul;130(1):276-278; author reply 278-279.22633321
45. Müller U, Schmid-Grendelmeier P, Hausmann O, Helbling A. IgE to recombinant allergens Api m 1, Ves v 1, and Ves v 5 distinguish double sensitization from cross reaction in venom allergy. Allergy. 2012 Aug;67(8):1069-1073.22676144
46. Korošec P, Valenta R, Mittermann I, et al. Low sensitivity of commercially available rApi m 1 for diagnosis of honeybee venom allergy. J Allergy Clin Immunol. 2011 Sep;128(3):671-673.21481443
47. Bazon ML, Silveira LH, Simioni PU, Brochetto-Braga MR. Current Advances in Immunological Studies on the Vespidae Venom Antigen 5: Therapeutic and Prophylaxis to Hypersensitivity Responses. Toxins (Basel). 2018 Jul 24;10(8):305.30042313
48. Seismann H, Blank S, Braren I, et al. Dissecting cross-reactivity in Hymenoptera venom allergy by circumvention of α-1,3-core fucosylation. Mol Immunol. 2010 Jan;47(4):799-808.19896717
49. Arzt L, Bokanovic D, Schrautzer C, et al. Questionable diagnostic benefit of the commercially available panel of bee venom components. Allergy. 2017 Sep;72(9):1419-1422.28273336
50. Blank S, Seismann H, Bockisch B, et al. Identification, recombinant expression, and characterization of the 100 kDa high molecular weight Hymenoptera venom allergens Api m 5 and Ves v 3. J Immunol. 2010 May 1;184(9):5403-5413.20348419
51. Jin C, Focke M, Leonard R, Jarisch R, Altmann F, Hemmer W. Reassessing the role of hyaluronidase in yellow jacket venom allergy. J Allergy Clin Immunol. 2010 Jan;125(1):184-190.19910026
52. Schiener M, Hilger C, Eberlein B, et al. The high molecular weight dipeptidyl peptidase IV Pol d 3 is a major allergen of Polistes dominula venom. Sci Rep. 2018 jan 22;8(1):1318.29358620
53. Blank S, Seismann H, Michel Y, et al. Api m 10, a genuine A. mellifera venom allergen, is clinically relevant but underrepresented in therapeutic extracts. Allergy. 2011 Oct;66(10):1322-1329.21658068
54. Frick M, Müller S, Bantleon F, et al. rApi m 3 and rApi m 10 improve detection of honey bee sensitization in Hymenoptera venom allergic patients with double sensitization to honey bee and yellow jacket venom. Allergy. 2015 Dec;70(12):1665-1668.26259841
55. Blank S, Etzold S, Darsow U, et al. Component-resolved evaluation of the content of major allergens in therapeutic extracts for specific immunotherapy of honeybee venom allergy. Hum Vaccin Immunother. 2017 Oct 3;13(10):2482-2489.28494206
56. Jakob T, Rauber MM, Perez-Riverol A, Spillner E, Blank S. The Honeybee Venom Major Allergen Api m 10 (Icarapin) and Its Role in Diagnostics and Treatment of Hymenoptera Venom Allergy. Curr Allergy Asthma Rep. 2020 Jun 16;20(9):48.32548726
57. Sturm GJ, Varga EM, Roberts G, et al. EAACI guidelines on allergen immunotherapy: Hymenoptera venom allergy. Allergy. 2018 Apr;73(4):744-764.28748641
58. Bonifazi F, Jutel M, Bilo BM, Birnbaum J, Muller U, EAACI Interest Group on Insect Venom Hypersensitivity. Prevention and treatment of hymenoptera venom allergy: guidelines for clinical practice. Allergy. 2005 Dec;60(12):1459-1470.16266376
59. King TP, Spangfort MD. Structure and biology of stinging insect venom allergens. Int Arch Allergy Immunol. 2000 Oct;123(2):99-106.11060481
60. Muller UR. Recombinant Hymenoptera venom allergens. Allergy. 2002 Jul;57(7):570-576.12100296
61. Blank S, Bazon ML, Grosch J, et al. Antigen 5 Allergens of Hymenoptera Venoms and Their Role in Diagnosis and Therapy of Venom Allergy. Curr Allergy Asthma Rep. 2020 Jul 9;20(10):58.32647993
62. Korošec P, Valenta R, Mittermann I, et al. High sensitivity of CAP-FEIA rVes v 5 and rVes v 1 for diagnosis of Vespula venom allergy. J Allergy Clin Immunol. 2012 May;129(5):1406-1408.22277201
63. Vos B, Köhler J, Müller S, Stretz E, Ruëff F, Jakob T. Spiking venom with rVes v 5 improves sensitivity of IgE detection in patients with allergy to Vespula venom. J Allergy Clin Immunol. 2013 Apr;131(4):1225-7, 1227.e1.23006544
64 Ebo DG, Faber M, Sabato V, Leysen J, Bridts CH, De Clerck LS. Component-resolved diagnosis of wasp (yellow jacket) venom allergy. Clin Exp Allergy. 2013 Feb;43(2):255-261.23331567
65. Seismann H, Blank S, Cifuentes L, et al. Recombinant phospholipase A1 (Ves v 1) from yellow jacket venom for improved diagnosis of hymenoptera venom hypersensitivity. Clin Mol Allergy. 2010 Apr 1;8:7.20359368
66. Henriksen A, King TP, Mirza O, et al. Major venom allergen of yellow jackets, Ves v 5: structural characterization of a pathogenesis-related protein superfamily. Proteins. 2001 Dec 1;45(4):438-448.
67. Sturm GJ, Bilo MB, Bonadonna P, et al. Ves v 5 can establish the diagnosis in patients without detectable specific IgE to wasp venom and a possible north-south difference in Api m 1 sensitization in Europe. J Allergy Clin Immunol. 2012 Sep;130(3):817; author reply 818-819.22795371
68. Bokanovic D, Schwarz I, Wutte N, Komericki P, Aberer W, Sturm GJ. Specificity of conventional and Ves v 5-spiked venom decreases with increasing total IgE. J Allergy Clin Immunol. 2014 Sep;134(3):739-741.24835504
69. Mittermann I, Zidarn M, Silar M, et al. Recombinant allergen-based IgE testing to distinguish bee and wasp allergy. J Allergy Clin Immunol. 2010 Jun;125(6):1300-1307.e3.20466415
70. Monsalve RI, Vega A, Marques L, et al. Component-resolved diagnosis of vespid venomallergic individuals: phospholipases and antigen 5 s are necessary to identify Vespula or Polistes sensitization. Allergy. 2012 Apr;67(4):528-536.22229815
71. Gattinger P, Lupinek C, Kalogiros L, et al. The culprit insect but not severity of allergic reactions to bee and wasp venom can be determined by molecular diagnosis. PLoS One. 2018 Jun 25;13(6):e0199250.29940036
72. 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 Sep;98(3):588-600.8828537
73. Schiener M, Eberlein B, Moreno-Aguilar C, et al. Application of recombinant antigen 5 allergens from seven allergy-relevant Hymenoptera species in diagnostics. Allergy. 2017 Jan;72(1):98-108.27496543
74. Jappe U, Raulf-Heimsoth M, Hoffmann M, Burow G, Hübsch-Müller C, Enk A. In vitro Hymenoptera venom allergy diagnosis: Improved by screening for cross-reactive carbohydrate determinants and reciprocal inhibition. Allergy. 2006 Oct;61(10):1220-1229.16942573
75. van Ree R. Carbohydrate epitopes and their relevance for the diagnosis and treatment of allergic diseases. Int Arch Allergy Immunol. 2002 Nov;129(3):189-197.12444315
76. Blank S, Neu C, Hasche D, Bantleon FI, Jakob T, Spillner E. Polistes species venomis devoid of carbohydrate-based cross-reactivity and allows interference-free diagnostics. J Allergy Clin Immunol. 2013 Apr;131(4):1239-1242.23228245
77. Selb J, Kogovsek R, Silar M, Košnik M, Korošec P. Improved recombinant Api m 1- and Ves v 5- based IgE testing to dissect bee and yellow jacket allergy and their correlation with the severity of the sting reaction. Clin Exp Allergy. 2016 Apr;46(4):621-630.26366855
78. Caruso B, Bonadonna P, Bovo C, et al. Wasp venom allergy screening with recombinant allergen testing. Diagnostic performance of rPol d 5 and rVes v 5 for differentiating sensitization to Vespula and Polistes subspecies. Clin Chim Acta. 2016 Jan 30;453:170-173.26719033
79. Savi E, Peveri S, Makri E, Pravettoni V, Incorvaia C. Comparing the ability of molecular diagnosis and CAPinhibition in identifying the really causative venom in patients with positive tests to Vespula and Polistes species. Clin Mol Allergy. 2016 Feb 8;14:3.26858583
80. Perez-Riverol A, Justo-Jacomini DL, Zollner Rde L, Brochetto-Braga MR. Facing Hymenoptera Venom Allergy: From Natural to Recombinant Allergens. Toxins (Basel). 2015 Jul 9;7(7):2551-2570.26184309
81. Quercia O, Cova V, Martini M, et al. CAP-inhibition, molecular diagnostics, and total IgE in the evaluation of polistes and vespula double sensitization. Int Arch Allergy Immunol. 2018;177(4):365-369.30176659
82. Bonadonna P, Scaffidi L. Hymenoptera anaphylaxis as a clonal mast cell disorder. Immunol Allergy Clin North Am. 2018 Aug;38(3):455-468.30007463
83. Hamilton RG. Diagnosis of Hymenoptera venom sensitivity. Curr Opin Allergy Clin Immunol. 2002 Aug;2(4):347-351.12130950
84. Vos BJPR, van Anrooij B, van Doormaal JJ, Dubois AEJ, Elberink JNGO. Fatal anaphylaxis to yellow jacket stings in mastocytosis: options for identification and treatment of at-risk patients. J Allergy Clin Immunol Pract. 2017 Sep-Oct;5(5):1264-1271.28499778
85. Ruëff F, Przybilla B, Biló MB, et al. Predictors of severe systemic anaphylactic reactions in patients with Hymenoptera venom allergy: importance of baseline serum tryptase-a study of the European Academy of Allergology and Clinical Immunology Interest Group on Insect Venom Hypersensitivity. J Allergy Clin Immunol. 2009 Nov;124(5):1047‐1054.19895993
86. Michel J, Brockow K, Darsow U, et al. Added sensitivity of component resolved diagnosis in hymenoptera venom-allergic patients with elevated serum tryptase and/or mastocytosis. Allergy. 2016 May;71(5):651-660.26836051
87. Fehr D, Micaletto S, Moehr T, Schmid-Grendelmeier P. Risk factors for severe systemic sting reactions in wasp (Vespula spp.) and honeybee (Apis mellifera) venom allergic patients. Clin Transl Allergy. 2019 Oct 11;9:54.31632639

For Providers

Please login to order a test

Order a Test

© 2021 Laboratory Corporation of America® Holdings and Lexi-Comp Inc. All Rights Reserved.

CPT Statement/Profile Statement

The LOINC® codes are copyright © 1994-2021, Regenstrief Institute, Inc. and the Logical Observation Identifiers Names and Codes (LOINC) Committee. Permission is granted in perpetuity, without payment of license fees or royalties, to use, copy, or distribute the LOINC® codes for any commercial or non-commercial purpose, subject to the terms under the license agreement found at Additional information regarding LOINC® codes can be found at, including the LOINC Manual, which can be downloaded at