Hymenoptera Venom Allergy Research Articles

Health disparities in hymenoptera venom allergy management.

Background: Hymenoptera venom anaphylaxis (HVA) is reported in up to 3% of stings and accounts for approximately 40 US deaths annually. HVA patients require immediate availability of epinephrine and Allergist referrals for consideration of venom immunotherapy. Data regarding epinephrine autoinjector prescriptions, Allergist referral rates, and potential racial disparities are limited. Objective: The primary objective was to determine if there were statistically significant differences in epinephrine autoinjector prescriptions and Allergist referrals between white and African American patients. The secondary objectives were to determine if there were statistically significant differences between adult and pediatric patients and to determine if there were significant differences between epinephrine prescriptions between patients with and without Allergist referrals. Method: This study is a retrospective, descriptive chart review analyzing patients seen between January 01, 2019 and December 31, 2021. Data were obtained utilizing the Epic Systems (Verona, WI) application Slicer Dicer. Individual chart review was performed for age, race, epinephrine autoinjector prescription, and Allergist referral. Results: 342 patients were identified as having HVA. White patients (60 out of 219; 27.4%) were more likely to get epinephrine autoinjector prescriptions than African American patients (17 out of 109; 15.6%) (p = 0.018). Adult patients (25 out of 314; 8.0%) were less likely than pediatric patients (8 out of 28; 28.6%) to have Allergist referrals (p = 0.004). Patients with Allergist referrals (25 out of 32; 78.1%) were more likely to be prescribed an epinephrine autoinjector than patient without Allergist referrals (54 out of 310; 17.4%) (p < 0.00001). Conclusion: Epinephrine autoinjector prescriptions and Allergist referrals are low overall in HVA. Racial disparities were identified with African American patients being significantly less likely to receive epinephrine autoinjector prescriptions. Additionally, adult patients, who may be at increased risk, were less likely to receive Allergist referrals.

Potential and limitations of epitope mapping and molecular targeting in Hymenoptera venom allergy.

Hymenoptera venom (HV) allergy can lead to life threatening conditions by specific IgE (sIgE)-mediated anaphylactic reactions. The knowledge about major allergens from venom of different clinically relevant species increased in the last decades, allowing the development of component-resolved diagnostics in which sIgE to single allergens is analysed. Despite these advances, the precise regions of the allergens that bind to IgE are only known for few HV allergens. The detailed characterization of IgE epitopes may provide valuable information to improve immunodiagnostic tests and to develop new therapeutic strategies using allergen-derived peptides or other targeted approaches. Epitope-resolved analysis is challenging, since the identification of conformational epitopes present in many allergens demands complex technologies for molecular analyses. Furthermore, functional analysis of the epitopeś interaction with their respective ligands is needed to distinguish epitopes that can activate the allergic immune response, from those that are recognized by irrelevant antibodies or T cell receptors from non-effector cells. In this review, we focus on the use of mapping and molecular targeting approaches for characterization of the epitopes of the major venom allergens of clinically relevant Hymenoptera species. The screening of the most relevant allergen peptides by epitope mapping could be helpful for the development of molecules that target major and immunodominant epitopes blocking the allergen induced cellular reactions as novel approach for the treatment of HV allergy.

Biologic drugs and allergen immunotherapy: potential allies

Allergen-specific immunotherapy (AIT) is a proven efficacy treatment for allergic rhinitis (AR), asthma, and Hymenoptera venom allergy, but its use in food allergy (FA) is still under investigation. Because some efficacy and safety concerns still remain, biologic drugs, including omalizumab and dupilumab, have been studied as an adjunctive therapy to AIT for these conditions. In this article, the evidence supporting the use of monoclonal antibodies (mAbs) as an add-on therapy to AIT for FA, AR, asthma, and Hymenoptera venom allergy has been reviewed. The review will delve into the mechanisms of action of different mAbs, their efficacy, and how they can be integrated into personalized medicine approaches to treat allergic diseases. Furthermore, future research areas will be considered. Evidence suggests that omalizumab in combination with AIT may be a beneficial option for respiratory allergies or food desensitisation, especially during the escalation or build-up phase, when adverse events are more frequent. Currently, there is a small number of well-structured clinical trials in Hymenoptera venom allergy, and the available data consist mainly of single-case reports that provide information of limited value. Dupilumab has been studied as adjunctive therapy in patients with respiratory and FAs. Clinical trials are ongoing to evaluate the efficacy of dupilumab as monotherapy or as an adjunct to oral immunotherapy (OIT) in peanut allergy. Other studies are investigating the use of dupilumab in patients with multiple FAs and as an adjunct to milk OIT. Overall, mAbs have the potential to improve outcomes in various allergic conditions when used as an add-on to AIT, especially during the build-up phase. Further research is needed to fully understand their optimal dosing and duration of treatment, as well as to identify which patients may benefit the most from these therapies.

Revealing clinically relevant specific IgE sensitization patterns in Hymenoptera venom allergy with dimension reduction and clustering

BackgroundImmunoglobulin E (IgE) blood tests are used to detect sensitizations and potential allergies. Recent studies suggest that specific IgE sensitization patterns due to molecular interactions affect an individual's risk of developing allergic symptoms. ObjectiveThe aim of this study was to reveal specific IgE sensitization patterns and investigate their clinical implications in Hymenoptera venom allergy. MethodsIn this cross-sectional study, 257 hunters or fishers with self-filled surveys on previous Hymenoptera stings were analyzed. Blood samples were taken to determine Hymenoptera IgE sensitization levels. Using dimensionality reduction and clustering, specific IgE for 10 Hymenoptera venom allergens were evaluated for clinical relevance. ResultsThree clusters were unmasked using novel dimensionality reduction and clustering methods solely based on specific IgE levels to Hymenoptera venom allergens. These clusters show different characteristics regarding previous systemic reactions to Hymenoptera stings. ConclusionOur study was able to unmask non-linear sensitization patterns for specific IgE tests in Hymenoptera venom allergy. We were able to derive risk clusters for anaphylactic reactions following hymenoptera stings and pinpoint relevant allergens (rApi m 10, rVes v 1, whole bee, and wasp venom) for clustering.

Basophil activation test (BAT) in double-sensitized patients with Hymenoptera venom allergy: additional benefit of component-resolved diagnostics.

In Hymenoptera venom allergy serologically double-sensitized patients it is often difficult to identify the culprit insect for venom immunotherapy (VIT). To evaluate if basophil activation tests (BATs) performed not only with venom extracts but additionally with single component-resolved diagnostics could differentiate between sensitized and allergic individuals and how the test results influenced the physicians' decision regarding VIT. BATs were performed with bee and wasp venom extracts and with single components (Api m 1, Api m 10, Ves v 1, Ves v 5) in 31 serologically double-sensitized patients. In 28 finally included individuals 9 BATs were positive and 4 negative for both venoms. 14/28 BATs showed positive results for wasp venom alone. 2/10 BATs positive for bee venom were only positive to Api m 1 and 1/28 BAT only to Api m 10, but not for whole bee venom extract. 5/23 BATs positive for wasp venom were only positive for Ves v 5, but negative for wasp venom extract and Ves v 1. Finally, VIT with both insect venoms was recommended in 4/28 individuals, with wasp venom alone in 21/28 patients and with bee venom alone in 1/28. In 2 cases no VIT was recommended. BATs with Ves v 5, followed by Api m 1 and Api m 10, were helpful for the decision for VIT with the clinically relevant insect in 8/28 (28.6%) patients. A BAT with components should therefore be additionally carried out in cases with equivocal results.

Severe food allergy reactions are associated with α-tryptase

Increased TPSAB1 copy numbers encoding ⍺-tryptase are associated with severe reactions in adults with Hymenoptera venom allergy, systemic mastocytosis, and idiopathic anaphylaxis. The primary objective was to assess the association between ⍺-tryptase and severity of food allergy. A total of 119 subjects underwent tryptase genotyping; 82 of them were from an observational food allergy cohort at the National Institute of Allergy and Infectious Disease (NIAID), and 37 were from a cohort of children who reacted to peanut oral food challenge (OFC) at Lurie Children's Hospital of Chicago. The primary predictor was presence or absence of ⍺-tryptase. The primary outcomes for both cohorts were measures of severity of food allergy reaction. Secondary outcomes included OFC symptom scores (Bock/Practical Allergy [PRACTALL] and Severity Grading Score for Acute Reactions [SGSAR]). Correlation between total α-tryptase isoforms and OFC scores was also assessed to account for gene dosage effects. Among the subjects in the NIAID cohort, the presence of ⍺-tryptase was associated with a higher prevalence of food-triggered anaphylaxis than in those with only β-tryptase (P= .026). Similarly, only 1 of 6 subjects in the OFC cohort with only β-tryptase (17%) had a severe reaction, whereas 20 of 31 of subjects with α-tryptase (65%) had a severe reaction (P= .066). Subjects with ⍺-tryptase also had higher total SGSAR scores than did the subjects with no ⍺-tryptase (P= .003). In addition, there were also significant positive correlations between ⍺-tryptase isoform copy numbers and both higher total SGSAR and Bock/PRACTALL OFC scores (P= .008 and P= .003, respectively). The presence of α-tryptase in subjects is correlated with a higher prevalence of anaphylaxis or severe reaction to food than in subjects without any α-tryptase.

Test di attivazione dei basofili (BAT): quale utilità nella diagnostica dell'allergia a veleno di imenotteri?

BACKGROUND: The diagnosis of Hymenoptera venom allergy (HVA) relies on detailed anamnesis, skin tests and determination of specific IgE (sIgE) with extractive and molecular allergens of Apidae and Vespidae. In many patients, however, multiple venoms sIgE positivity is detected and it is not always possible to clearly determine the primary sensitization or whether there is true double sensitization, and therefore to prescribe a proper venom-specific immunotherapy (VIT). In these cases, the in vitro sIgE inhibition test can add valuable information. However, this test requires extensive experience and has some limitations in case of low sIgE values and in case of high levels of sIgE anti-cross reactive carbohydrate determinants (CCD). Recently, the use of basophil activation test (BAT) has been recommended in order to identify the primary sensitization in subjects in which molecular testing and/or sIgE inhibition have been inconclusive. Aim of the study was to evaluate the usefulness of BAT in a selected cohort of subjects who experienced allergic reactions following hymenoptera sting, history suggestive of Vespid sting and inconclusive sIgE assay.METHODS: Nineteen subjects with allergic reactions following hymenoptera sting (17 with systemic reactions and two with extensive local reactions) were studied. Of those, six patients showed multiple sIgE positivity for Vespidae and positivity sIgE for Apis mellifera (Apis m) and anti-CCD (5/6) too; six patients complained reactions after hymenoptera sting but with negativity of Apis m and Vespidae sIgE (≤0.10 kU/L), and seven patients showed very low sIgE levels (0.11-0.84 kU/L) for extractive and/or molecular Vespidae allergens. In all subjects, the following were performed: the sIgE assay for Vespula sp, Polistes dominulus (Polistes d), Vespa crabro, Apis m, Ves v 1, Ves v 5 and Pol d 5 (ImmunoCAP 1000, Thermofisher Scientific), and BAT in which extractive venoms of Vespula sp (BAG2-I3) and Polistes d (BAG2-I77), (Bühlmann Laboratories AG), were used for basophil stimulation. The response, measured as percentage of activated basophils (CD63+) at the different venom concentrations, was evaluated by cytofluorimetric method with FACSCanto™ II (Becton Dickinson). The sIgE inhibition assay was performed by overnight incubation at 4 °C of serum with venom extract in solution (Anallergo), at decreasing concentrations of 300, 30, 3 and 0.3 µg/mL, followed by sIgE assay.RESULTS: BAT detected the primary sensitizer in 6/19 (32%) subjects including one with negative sIgE and three with very low sIgE, while sIgE assay identified the primary sensitizer in 5/19 (26%) including four concordant with BAT. BAT in 6/19 (32%) cases allowed diagnosis of dual sensitization, of which half (3/6) confirmed by inhibition test, five concordant with sIgE assay by molecular technique, and one with negative sIgE. In one of seven cases of dual sensitization evidenced by molecular testing, BAT was decisive and in one case negative. In 2/7 (29%) patients with negative sIgE for molecular allergens, BAT was positive for Vespula sp (in one of these, similar activation was obtained for Vespula sp and Polistes d at different venom concentrations).CONCLUSIONS: This study proved that BAT is useful in confirming true double sensitizations and slightly more sensitive than molecular testing in identifying single sensitization to Vespidae venom, both in cases with negative sIgE (≤ 0.10 kU/l), and in subjects with multiple positivities for Vespidae, even where anti-CCD antibodies are present. These data, therefore, confirm the importance of combining multiple laboratory methods for precision diagnosis of HVA and more accurate choice of VIT.

Updates and Recent Advances on Venom Immunotherapy.

Venom immunotherapy has been utilized to treat Hymenoptera venom allergy since the 1920s. Over the last century, significant advances in the fields of immunology and genetics have led to improvements in the practice of venom immunotherapy. This review encompasses recent advances in the use of venom immunotherapy to provide precise, patient-centered care. Research about the mechanism of action of venom immunotherapy continues to highlight the modification of both the innate and adaptive immune systems. Molecular techniques have allowed for the identification of specific venom allergens to improve the diagnostic accuracy and safety of venom immunotherapy. Research continues to support the safety of accelerated schedules which can impact the cost, adherence, and quality of life for patients receiving this treatment modality. Finally, significant advances have led to the elucidation of risk factors that place patients at risk for reactions during and after venom immunotherapy. Creation of risk profiles for venom-allergic patients can thus inform the process of immunotherapy in order to provide personalized and precise care. Significant progress in the use of venom immunotherapy makes the practice a dynamic and active field for continued research. Future research needs to build on these recent advances to continue to optimize and enhance this life-saving treatment.

Molecular diagnostics and inhibition of cross-reactive carbohydrate determinants in Hymenoptera venom allergy.

The composition of venom extracts, cross-reactive carbohydrate determinants (CCD) and the component-resolved diagnostics (CRD) are important fields of investigation. IgE-reactivity to CCD complicates the interpretation of IgE to Hymenoptera venoms, especially in patients with multiple-positivity. We analyzed the clinical importance of CRD and CCD-inhibition for selection of allergens for venom immunotherapy (VIT). In 71 patients, we measured specific IgE (sIgE) to honeybee venom (HBV), wasp venom (WV), hornet venom (HV), CCD, and recombinant allergens: phospholipase A2 (rApi m 1), hyaluronidase (rApi m 2), icarapin (rApi m 10), antigen 5 (rVes v 5), and phospholipase A1 (Immunoblot). In 29/71 HBV/WV/HV/CCD-positive patients CCD-inhibition was performed. According to CRD and CCD-inhibition, we identified true sensitization and defined groups of multiple-positive patients who needed CCD-inhibition before starting VIT. sIgE-rApi m 1, sIgE-rApi m 2, and sIgE-rApi m 10 were detected in 65.7%, 68.4%, and 58%, respectively. In HBV allergic patients, CRD sensitivity was 86.8%. In WV allergic patients, sensitivity of sIgE-rVes v 5 was 94%. True multiple-sensitization was found in 44.8% of HBV/WV/HV/CCD-positive patients after CCD-inhibition. Patients with multiple venom- and CCD-positivity had more frequent severe allergic reactions (p<0.001). CCD-inhibition was helpful in HBV/WV/HV/CCD-positive patients who were negative to all tested recombinant honeybee allergens. Persistence of HBV-positivity after CCD-inhibition requires CRD to other honeybee recombinant allergens. CRD, using a profile of five most important recombinant allergens and CCD, has a high sensitivity for the diagnosis of venom allergy, especially in patients positive to several venom extracts. CRD and CCD-inhibition are helpful to reveal the clinically relevant, true sensitization and improve the selection of venoms for long-lasting VIT.

Investigation of Tryptase Gene Composition as a Potential Biomarker of Food Allergy Reaction Severity

Increased TPSAB1 copy number encoding ⍺-tryptase is associated with severe reactions in adults with Hymenoptera venom allergy, systemic mastocytosis, and idiopathic anaphylaxis. Tryptase gene composition as a potential biomarker for food allergy severity has not been studied. We hypothesized that increased relative TPSAB1 copy number encoding ⍺-tryptase would be enriched in children with severe reactions to peanut.

Stinging insect identification in children with Hymenoptera venom allergy and their parents.

The treatment of Hymenoptera venom allergy (HVA) is based among others on the proper identification of the culprit insect. To assess the accuracy in identifying stinging insects by children with HVA and their parents. Participants were recruited from a paediatric medical centre. The data on their demographics, sting history and ability of insect identification (based on pictures) were obtained using a questionnaire. The study sample consisted of 102 children with HVA and their parents as well as 98 children without HVA and their parents. The rates of subjects correctly identifying insects in the groups were 91.2%, 92.5%, 78.8%, 82.4%, respectively. When compared to children with HVA, those without HVA were less likely to correctly identify the bee, bumblebee and hoverfly. In this group, the correct identification of the wasp was more common among children living in the countryside. The correct identification of the bee and bumblebee by children without HVA was more common among children living in the city. Some children with HVA and their parents cannot correctly identify stinging insects despite previous life-threatening allergic reactions. The ability to identify stinging insects may depend on the HVA diagnosis and place of residence.

Imunoterapija kod pacijenata sa prvim tipom preosetljivosti na Hymenoptera venome

Hymenoptera venom allergy (HVA) is an anaphylactic reaction that occurs after the sting of Hymenoptera insects: honeybee (Apis mellifera), wasp (Vespula vulgaris) or hornet (Vespa crabo). Hymenoptera insects can cause IgE-mediated hypersensitivity reactions in insect-sensitized patients, ranging from local to severe systemic reactions and even fatal anaphylaxis. Systemic allergic reactions (SAR) after Hymenoptera insect stings have been reported in up to 7.5% of adults and up to 3.4% of children. They can be limited to the skin or cause severe reactions such as dizziness, dyspnea, nausea, and loss of consciousness, shock, cardiac or respiratory arrest. Patients with HVA are advised to carry an emergency kit consisting of an epinephrine auto-injector (AAI), H1-antihistamines and corticosteroids depending on the severity of the previous SAR. The only treatment that can potentially prevent SAR is immunotherapy with the appropriate venom (VIT). Venom immunotherapy (VIT) has been reported to be effective in 77%-84% of patients treated with bee venom and in 91%-96% of patients treated with wasp venom. The latest European Academy of Allergy and Clinical Immunology (EAACI) guidelines provide evidence-based recommendations for the use of VIT. It is recommended in children and adults who are hypersensitive to the venom because it leads to a significant improvement in quality of life-compared to wearing an adrenaline auto-injector. By receiving increasing doses of venom over 3 to 5 years, VIT leads to a change in the immune response and tolerance to the respective venom. Molecular diagnostics, which uses recombinant allergens, enables detection of true sensitization and thus improves the selection of appropriate venom for long-term VIT. This review aims to provide information on immunotherapy recommendations, as well as risk factors for SAR during and after VIT.

Allergen immunotherapy of insect venom allergy: Almost 100 years old, but steadily updated.

llergen immunotherapy (AIT) with Hymenoptera venom (HV) shows high efficiency treating insect venom allergy, covering an almost 100-year-long history. Untreated patients with HV allergy can develop serious, potentially lethal sting reactions. Before starting AIT with HV, indication and contraindications, the presence of comorbidities and the intake of concomitant medications as well as individual risk factors have to be carefully evaluated. Application of HV-AIT entails an individually adapted procedure in case of undesired adverse events or initial failure to induce tolerance, as the final goal has to be the development of immunologic protection against anaphylactic sting reactions.

COVID-19 vaccination safety in patients with hymenoptera venom allergy referred by primary health care

COVID-19 vaccination safety in patients with hymenoptera venom allergy referred by primary health care

Diagnosis and treatment of Hymenoptera venom allergy: S2k Guideline of the German Society of Allergology and Clinical Immunology (DGAKI) in collaboration with the Arbeitsgemeinschaft für Berufs- und Umweltdermatologie e.V. (ABD), the Medical Association of German Allergologists (AeDA), the German Society of Dermatology (DDG), the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNOKC), the German Society of Pediatrics and Adolescent

Diagnosis and treatment of Hymenoptera venom allergy: S2k Guideline of the German Society of Allergology and Clinical Immunology (DGAKI) in collaboration with the Arbeitsgemeinschaft für Berufs- und Umweltdermatologie e.V. (ABD), the Medical Association of German Allergologists (AeDA), the German Society of Dermatology (DDG), the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNOKC), the German Society of Pediatrics and Adolescent

Mast Cell Activation Syndromes: Comparison Between Two Scoring Models to Predict for Mast Cell Clonality

The Red Española de Mastocitosis (Spanish Network on Mastocytosis) score (REMAs) and the National Institutes of Health idiopathic clonal anaphylaxis score (NICAS) were developed for more efficient screening of mast cell (MC) clonality in MC activation syndromes. In a limited idiopathic anaphylaxis case series, the NICAS showed higher accuracy compared with the REMAs. To compare the performance of the REMAs against the NICAS in the diagnosis of MC clonality. We compared the diagnostic value of the REMAs against the NICAS in 182 patients (63% men, median age 56 years) who presented with anaphylaxis triggered by Hymenoptera venom allergy (45%), drugs (15%), food (11%), idiopathic anaphylaxis (20%), and mixed causes (10%). KIT mutation was assessed in parallel in whole blood and bone marrow (BM) and, when negative, in highly purified BM MC. TPSAB1 was genotyped in a subset of 71 patients. We found higher accuracy and rates of correctly classified patients for the REMAs (82% and 84%) compared with the NICAS (75% and 75%; P= .02 and P= .03, respectively), particularly among men (P= .05), patients with systemic mastocytosis (P= .05), those presenting anaphylaxis owing to any cause featuring urticaria (P= .04), cardiovascular symptoms (P= .02), and/or presyncope (P= .02) and those with a blood-negative/BM-positive KIT mutational profile (P= .002), but not hereditary α-tryptasemia-associated genotypes. Combined assessment of the REMAs and KITD816V in blood yielded an overall improved classification efficiency of 86% versus 84% for REMAs. The combined use of the REMAs and blood detection of KITD816V is recommended, but more sensitive blood-based molecular assays to detect KITD816V are needed.

Adverse reactions in venom immunotherapy protocols: conventional versus ultra-rush

Background Venom immunotherapy (VIT) is an effective treatment in the patients at high risk of anaphylaxis or life-threatening systemic reactions due to Hymenoptera venom allergy. But, systemic and large local reactions can be observed, especially during the build-up phase of VIT. We evaluated the safety of conventional and ultra-rush build-up protocols. Materials and methods Two protocols in 71 patients (39 conventional and 32 ultra-rush protocols) with honeybee and wasp venom allergy were evaluated retrospectively. Patients were diagnosed and selected for VIT according to the criteria established by the European Academy of Allergy and Clinical Immunology. The severity of systemic reactions was evaluated according to the criteria of Mueller. Results Build-up phases were tolerated in 66.2% (n = 47) without any reaction. Allergic adverse reactions were observed in 33.8% (n = 24): large local reactions 22.5% (n = 16) and systemic reactions 11.3% (n = 8). There was no significant difference in the number of adverse reactions comparing patients receiving conventional and ultra-rush protocol. In addition, no association was found between allergic adverse reactions and the following factors: sex, previous systemic sting reactions, honeybee and wasp venom extract. Conclusion We found that both protocols were tolerated in patients with honeybee and wasp venom allergy. Ultra-rush protocol will be preferred for patients and clinicians because of its advantages in terms of time and costs. KEY MESSAGES VIT is the only curative treatment method that reduces the risk of severe reactions after a bee sting and improves the quality of life in patients with Hymenoptera venom allergy. Ultra-rush VIT protocol has advantages such as few injection and time savings. Both ultra-rush and conventional VIT are safe treatments to prevent potentially life-threatening reactions in patients with honeybee and wasp venom allergy.

Diagnosis of Hymenoptera Venom Allergy: State of the Art, Challenges, and Perspectives.

Hymenoptera venom allergy is the most common cause of anaphylaxis in adults and the second-most frequent in children. The proper diagnosis of this life-threatening allergy remains a challenge. This review focuses on the current knowledge regarding diagnostics of Hymenoptera venom allergy. The paper includes a brief description of the representatives of Hymenoptera order and the composition of their venoms. Then, diagnostic tests for allergy to Hymenoptera venom are described. Common diagnostic problems, especially double positivity in tests for IgE antibodies specific to honeybee and wasp venom, are also discussed. Special attention is paid to the search for new diagnostic capabilities using modern methodologies. Multidimensional molecular analysis offers an opportunity to characterize changes in body fluids associated with Hymenoptera venom allergy and yields a unique insight into the cell status. Despite recent developments in the diagnostics of Hymenoptera venom allergy, new testing methodologies are still needed to answer questions and doubts we have.

Long-term efficacy of the sublingual and subcutaneous routes in allergen immunotherapy.

Allergen immunotherapy is highly effective in selected patients with allergic rhinitis, allergic asthma, and Hymenoptera venom allergy. Unlike anti-allergic drugs, both subcutaneous and sublingual immunotherapies have been shown to modify the underlying cause of the disease, with proved long-term clinical benefits after treatment cessation. In this review, we analyzed 10 randomized, double-blind, placebo controlled clinical trials of allergen immunotherapy that included blinded follow-up for at least 1 year after treatment withdrawal. Three studies of pollen subcutaneous immunotherapy provided evidence that a sustained, tolerogenic effect of subcutaneous immunotherapy can be achieved after 3 years of treatment. Six trials of sublingual immunotherapy provided robust evidence for long-term clinical benefit and persistent immunologic changes after grass pollen, house-dust mite, or Japanese cedar immunotherapy, whereas a clinical trial of both sublingual and subcutaneous grass pollen immunotherapies showed that 2 years of immunotherapy were efficacious but insufficient to induce long-term tolerance. These studies strongly supported international guidelines that recommend at least 3 years of allergen immunotherapy of proven value to achieve disease modification and sustained clinical and immunologic tolerance.

Basophil activation test as alternative method to CAP-inhibition in patients with double sensitization to vespid venoms

Most patients with Hymenoptera venom allergy (HVA) to vespid venoms present double sensitization by specific IgE (sIgE)-mediated cross-reactivity. Thus, it is mandatory could discriminate between a true double and primary sensitization to implement an accurate venom-specific immunotherapy (VIT). To date, CAP-inhibition is the reference method in the diagnosis of cross-reactivity in double sensitized patients to vespid venoms, being the results obtained with the component resolved diagnostics (CRD) conflicting. For this, we have studied in a cohort of double sensitized patients to Vespula vulgaris (VV) and Polistes dominulus (PD) venoms (n = 40) the diagnostic accuracy of CRD using the CAP-inhibition as reference method, as well as to investigate whether basophil activation test (BAT) is an alternative method for inconclusive results obtained by CAP-inhibition. CAP-inhibition showed a sensitivity of 59.46 % in view of the indeterminate results; most patients had true double sensitization (54.5 %), followed by single sensitization to PD (27.27 %) and VV (18.18 %) venoms. CRD based on rVes v 5/rPol d 5 (or vice versa) ratio as well as whole extracts I3/I77 (or vice versa) ratio (specific IgE-I3 to VV/specific IgE-I77 to PD) showed a low diagnostic accuracy (AUC = 0.504, p = 0.974; AUC = 0.35, p = 0.235; respectively). BAT was determined in parallel with CAP-inhibition in 12 patients, presented higher sensitivity than CAP-inhibition (p = 0.021) and a positive agreement of 71.43 %. Likewise it was able to identify 100% of inconclusive results, showing a specificity of 83.3 %. Therefore, CRD is not a suitable method to distinguish monosensitization and BAT appears to be an appropriate method resolving indeterminate results from the gold standard method.