Api m 6 and Api m 10 as Major Allergens in Patients With Honeybee Venom Allergy.

BACKGROUND: Component-resolved diagnosis plays a key role in the diagnosis and treatment of honeybee venom allergy (HVA). Our aim was to study whether any of the allergens not included in the usual diagnostic platforms are relevant in our population. MATERIAL AND METHODS: The allergenic sensitization profile of Spanish patients who experienced a systemic reaction after a honeybee sting and were diagnosed with HVA was studied by immunoblotting based on raw autochthonous Apis mellifera venom characterized using SDS-PAGE and mass spectrometry and a commercial assay (ImmunoCAP). RESULTS: Allergens in the International Union of Immunological Societies database were detected in the raw A mellifera venom extract used, except Api m 12. Sera from 51 patients with a median (IQR) age of 46.2 years (35.6-54.6) were analyzed. ImmunoCAP revealed Api m 1 and Api m 10 to be major allergens (88.2% and 74.5%, respectively). Moreover, Api m 6 (85.4%) was detected by immunoblotting. CONCLUSION: Api m 1, Api m 6, and Api m 10 are major A mellifera venom allergens in our population.

An Increase in Tryptase on the First Day of Hymenoptera Venom Immunotherapy Might Be a Predictor of Future Systemic Reactions During Treatment.

BACKGROUND AND OBJECTIVE: Serum tryptase (ST) decreases during long-term venom immunotherapy (VIT). ST also exhibits a circadian variation, with a small decrease after sting challenge. Both findings have been related to successful VIT. Objective: To assess whether variation (increase or decrease) in ST on the first day of VIT is associated with the likelihood of future systemic adverse reactions (SARs) during treatment. METHODS: We prospectively studied patients who underwent cluster VIT, which was continued for at least 6 months. ST was measured on the first day of VIT, before the first dose (pre-IT tryptase) and after the last dose (post-IT tryptase). Differences between patient groups (with and without SAR) were analyzed. RESULTS: A total of 160 courses of VIT were administered to 150 patients. The median baseline ST value was 4.3 µg/L. A total of 25 courses (15.6%) were associated with SAR. In 64% of the 25 patients with SAR, the post-IT tryptase value was higher than the pre-IT tryptase level; the median increment was 19% in these patients. We found a significant association between the increase in ST on the first day of VIT and future SARs (risk ratio, 7.6). This elevation was independent of the scheduled VIT day, severity of the SAR, and baseline ST value. CONCLUSIONS: A slight increase in tryptase on the first day of VIT is an independent variable that is strongly related to a high risk of future SAR. This simple biomarker could improve patient safety.

Component-resolved diagnosis in hymenoptera allergy.

Component-resolved diagnosis based on the use of well-defined, properly characterised and purified natural and recombinant allergens constitutes a new approach in the diagnosis of venom allergy. Prospective readers may benefit from an up-to-date review on the allergens. The best characterised venom is that of Apis mellifera, whose main allergens are phospholipase A2 (Api m1), hyaluronidase (Api m2) and melittin (Api m4). Additionally, in recent years, new allergens of Vespula vulgaris have been identified and include phospholipase A1 (Ves v1), hyaluronidase (Ves v2) and antigen 5 (Ves v5). Polistes species are becoming an increasing cause of allergy in Europe, although only few allergens have been identified in this venom. In this review, we evaluate the current knowledge about molecular diagnosis in hymenoptera venom allergy.

Key Issues in Hymenoptera Venom Allergy: An Update.

In this review, the Hymenoptera Allergy Committee of the SEAIC analyzes the most recent scientific literature addressing problems related to the diagnosis of hymenoptera allergy and to management of venom immunotherapy. Molecular diagnosis and molecular risk profiles are the key areas addressed. The appearance of new species of hymenoptera that are potentially allergenic in Spain and the associated diagnostic and therapeutic problems are also described. Finally, we analyze the issue of mast cell activation syndrome closely related to hymenoptera allergy, which has become a new diagnostic challenge for allergists given its high prevalence in patients with venom anaphylaxis.

Insect Venom Immunotherapy: Analysis of the Safety and Tolerance of 3 Buildup Protocols Frequently Used in Spain.

INTRODUCTION: Hymenoptera venom immunotherapy (VIT) is an effective treatment but not one devoid of risk, as both local and systemic adverse reactions may occur, especially in the initial phases. We compared the tolerance to 3 VIT buildup protocols and analyzed risk factors associated with adverse reactions during this phase. MATERIALS AND METHODS: We enrolled 165 patients divided into 3 groups based on the buildup protocol used (3, 4, and 9 weeks). The severity of systemic reactions was evaluated according to the World Allergy Organization model. Results were analyzed using exploratory descriptive statistics, and variables were compared using analysis of variance. RESULTS: Adverse reactions were recorded in 53 patients (32%) (43 local and 10 systemic). Local reactions were immediate in 27 patients (63%) and delayed in 16 (37%). The severity of the local reaction was slight/moderate in 15 patients and severe in 13. Systemic reactions were grade 1-2. No significant association was found between the treatment modality and the onset of local or systemic adverse reactions or the type of local reaction. We only found a statistically significant association between severity of the local reaction and female gender. As for the risk factors associated with systemic reactions during the buildup phase, we found no significant differences in values depending on the protocol used or the insect responsible. CONCLUSIONS: The buildup protocols compared proved to be safe and did not differ significantly from one another. In the population studied, patients undergoing the 9-week schedule presented no systemic reactions. Therefore, this protocol can be considered the safest approach.

Evaluation of basophil activation in mastocytosis with Hymenoptera venom anaphylaxis.

BACKGROUND: Basophil activation tests (BATs) have been demonstrated to be useful in detecting IgE-mediated sensitization by measuring basophil activation surface markers (CD63 and CD203c). Hymenoptera venom is one of the best known mediators-release trigger in patients with systemic mastocytosis (SM). The aim of this study was to investigate the use of BATs as an additional diagnostic tool in patients with mastocytosis suffering from hymenoptera venom anaphylaxis (HVA). METHODS: A total of 22 patients with history of HVA and SM, together with a group of 11 patients with HVA in whom SM was ruled out after a complete bone marrow study, were analyzed. RESULTS: Among 11 SM patients who had specific serum IgE (sIgE) against hymenoptera venom and an evaluable BAT, a positive BAT was found in nine. Additionally, a positive BAT was detected in three of seven patients who had no sIgE. These three patients had low levels of total IgE compared with control population (mean of 20 vs. 78 IU/mL); one had discontinued immunotherapy after 5 years, when sIgE levels had turned negative, and, in the other two patients, BAT identified the culprit insect. CONCLUSIONS: BAT is a useful complementary diagnostic tool to sIgE in mastocytosis patients with HVA, and it may contribute to predict or confirm these nearly fatal reactions, especially before discontinuing venom immunotherapy in patients who are negative for skin tests or sIgE or display low total IgE levels; in such cases, it also provides evidence on the culprit insect prompting HVA.