Dipeptidyl peptidase IV of the Vespa velutina nigrithorax venom is recognized as a relevant allergen.

BACKGROUND: Vespa velutina nigrithorax (VVN), typically known as the Asian yellow-legged wasp, has been one of the most significant invasive species in western Europe since 2010. Currently, VVN has become the most prevalent cause of Hymenoptera anaphylaxis in the north and northwestern Spain. For this reason, it is crucial to diagnose anaphylaxis cases in the acute moment for carrying out the best available treatment as soon as possible. OBJECTIVE: To achieve a complete understanding of the venom allergen composition that will help to develop efficient diagnostics and immunotherapy treatments on the basis of this venom. METHODS: In this study, autochthonous VVN venom was obtained and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, isoelectric focusing, followed by a mass spectrometry analysis. In addition, the allergenic sensitization profile of patients diagnosed with allergy to VVN in the Allergology Service of Navarra University Hospital between the years 2017 and 2020 was studied by immunoblotting and specific IgE (ImmunoCAP, Thermo Fisher Scientific, Uppsala, Sweden). RESULTS: Two new allergens (dipeptidyl peptidase IV and serin protease) were identified in the autochthonous VVN venom, and their identity was confirmed by liquid chromatography-mass spectrometry analysis. The study by ImmunoCAP using sera from 12 patients who had a systemic reaction after a VVN sting revealed groups 5 and 1 as predominant allergens (92% and 34%, respectively). Furthermore, the immunoblotting assay recognized dipeptidyl peptidase IV (50%) in the sera of these patients. CONCLUSION: Serine protease and the dipeptidyl peptidase IV are components of the VVN venom, and the latter is an allergen recognized in the studied population.

Double-blind, randomized, placebo-controlled trial of allergen-specific immunotherapy with the major allergen Alt a 1.

BACKGROUND: There have been few studies conducted on the efficacy and safety of specific immunotherapy with allergen extracts of fungi compared with other allergen extracts, and there are no data on the major allergen Alt a 1 of the fungus Alternaria alternata. OBJECTIVES: We sought to evaluate the efficacy and safety of subcutaneous immunotherapy with 2 different doses of Alt a 1 in patients with rhinoconjunctivitis caused by sensitization to A alternata. METHOD: We performed a multicenter, randomized, double-blind, placebo-controlled trial with Alt a 1 administered subcutaneously in patients with allergic rhinoconjunctivitis with or without controlled asthma aged 12 to 65 years. Three groups were included: the placebo group and active groups receiving 0.2 or 0.37 µg of Alt a 1 per dose. The main end point was the combined symptom and medication score. Secondary end points were cutaneous reactivity and serum IgE and IgG4 levels to Alt a 1. Recorded adverse reactions were graded according to World Allergy Organization criteria. RESULTS: There were significant reductions in the combined symptom and medication score for the 0.37-µg dose of Alt a 1 compared with placebo at 12 months of treatment. Reduced cutaneous reactivity and IgE levels, together with increased IgG4 levels, were demonstrated for the 2 active groups versus the placebo group. A similar safety profile was found for both active groups compared with the placebo group. No serious adverse drug reactions were reported. CONCLUSION: Immunotherapy with Alt a 1 was efficacious and safe, reducing the symptoms and medication consumption associated with rhinoconjunctivitis after only 1 year of treatment. The clinical benefits were associated with reduced skin reactivity and specific IgE levels and increased IgG4 levels.

Decision-making for pediatric allergy immunotherapy for aeroallergens: a narrative review.

There has been exciting progress in diagnosis and in the treatment of allergic patients. The objective of this review is to summarize the most relevant contributions in the past 10 years with a special focus on the pediatric population allergic to aeroallergens and provide the most relevant references and practical issues for the decision-making. Current guidelines on allergy diagnosis recommend a thorough clinical history as the first step, followed by allergen extract testing using an in vivo prick test and/or an in vitro specific IgE test. Molecular diagnosis is recommended when previous tests are inconclusive. In practice, the most important factors to decide the AIT treatment are the actual intensity and duration of the patient's symptoms and the availability of appropriate AIT products for the patient's sensitization profile at high allergen concentrations and with confirmed efficacy and safety from clinical trials. This document summarizes outstanding references for allergic immunotherapy decision-making and provides summary tables and figures analyzing the most important factors related to the decision for allergen immunotherapy and the safety risks related. The experts concluded that AIT is efficacious and safe for the treatment of allergic patients that is available for the most frequent aeroallergens.What is Known:• The prevalence of allergic asthma and rhinitis in children has increased in recent decades.• The efficacy and safety of allergen immunotherapy has been shown in multiple studies and systematic reviews.What is New:• This document summarizes outstanding references for allergic immunotherapy decision-making and provides summary tables and figures analyzing the most important factors related to the decision for allergen immunotherapy and the safety risks related. Recommendations of expert authors for the decision of the patients more suitable for allergen immunotherapy are included.

Comparison of conventional and component-resolved diagnostics by two different methods (Advia-Centaur/Microarray-ISAC) in pollen allergy.

BACKGROUND: Component-resolved diagnostics (CRD) has recently been introduced into clinical allergology. OBJECTIVE: The aim of this study was to assess the contribution that this new diagnostic technique makes to conventional diagnosis in patients with pollen allergy, comparing CRD with conventional technologies, and to compare 2 CRD methods, Advia-Centaur and Microarray-ISAC. METHODS: Serum samples from 120 pollen-allergic patients were obtained. Immunoglobulin (Ig) E to total extracts (CAP System) and individual allergens using both CRD methods were determined. RESULTS: The 3 diagnostic methods were in agreement in 62.5% of cases. In 30%, the CRD modified the conventional diagnosis either by detecting new relevant sensitizations (mainly to Olea) or by ruling out clinically irrelevant sensitizations caused by panallergens. The main differences between the 2 CRD methods were the deficiency in the ISAC version we used (ISAC-CRD-89) to detect sensitizations to Salsola and Plantago and that Advia-Centaur did not detect sensitizations to cypress. For all allergens except for Par j 1, a significant association in the frequency of sensitization was seen with the 2 CRD techniques and good agreement when comparing the results of the 2 methods in all cases. Significant correlation was found in the concentration of specific IgE in the 2 techniques for the most prevalent allergens in our setting. The results of the different profilins analyzed using Microarray-ISAC were superimposable although somewhat lower in the case of Phl p 12. CONCLUSIONS: Component-resolved diagnostics modified the conventional diagnosis in 30% of cases. The results from the 2 CRD methods showed good agreement and correlation for most allergens.

Double-blind, placebo-controlled Alternaria alternata immunotherapy: in vivo and in vitro parameters.

Few studies have been published on the efficacy and safety of immunotherapy with fungal extracts, possibly because of difficulties arising from antigenic variability among different strains of fungus. The aim of the study was to analyze changes in the in vivo and in vitro parameters in response to immunotherapy with an Alternaria alternata extract. We studied 28 patients with rhinitis, bronchial asthma, or both caused by Alternaria. The patients were randomized to the active immunotherapy or placebo group, and a conventional schedule of immunotherapy was used. We recorded changes for a year in skin reactivity (skin prick test), conjunctival reactivity (conjunctival provocation test), and in vitro parameters (serum-specific IgE, IgG, IgG1 and IgG4 for A. alternata complete extract and for natural and recombinant Alt a 1). Twenty-three patients completed the study and all attained the maintenance dose. There were no changes in skin reactivity in the active treatment group, and reactivity increased at the end of the study period in the placebo group. Conjunctival sensitivity decreased only in the active treatment group when the maintenance dose was reached. Allergen-specific IgE decreased, and IgG, IgG1 and IgG4 increased in all periods of study in the active treatment group, with no changes in the placebo group. Allergen-specific immunotherapy with the A. alternata extract tested here led to a decrease in conjunctival reactivity and induced a significant immunologic response.

Specific immunotherapy with standardized latex extract versus placebo in latex-allergic patients.

BACKGROUND: Allergy to natural rubber latex proteins continues to be an important medical problem among health care professionals, but also in multioperated children. Clinical manifestations range from urticaria to angioedema, rhinoconjunctivitis, bronchial asthma and anaphylactic shock. METHODS: The aim of this study was to investigate the efficacy and safety of a 12-month latex-specific immunotherapy in sensitized patients, most often health care workers. Twenty-three patients with latex rhinoconjunctivitis (20 of whom also had asthma) were included in this randomized, double-blind, placebo-controlled trial (11 in the active group, 12 in the placebo group). Treatment efficacy was assessed by means of symptom and medication scores. Conjunctival provocation tests and quantitative skin prick tests were also performed. RESULTS: The clinical index (derived by combining changes from baseline of six efficacy variables during the treatment period) did not differ significantly between treatment groups. Change from baseline of rhinitis, conjunctivitis, skin symptoms, asthma symptoms, medication score and cutaneous reactivity were not significantly different between the two groups. A nonsignificant difference in conjunctival reactivity was observed in favor of the active group (p = 0.09). Systemic reactions were much higher in the specific immunotherapy than in the placebo group. CONCLUSIONS: The present study failed to show a significant improvement of symptoms and medication scores, probably because of the low level of symptoms at baseline and the low maintenance dose of therapy, even if allergen-specific conjunctival reactivity decreased in the active group. Moreover, the incidence of systemic reactions was very high in the active group.

Double-blind comparative study of cluster and conventional immunotherapy schedules with Dermatophagoides pteronyssinus.

BACKGROUND: The conventional schedule for subcutaneous immunotherapy with allergen extracts, although efficacious and safe, is slow during the dose-increase phase. OBJECTIVE: We sought to compare the efficacy and safety of subcutaneous immunotherapy with Dermatophagoides pteronyssinus standardized extract given in a 6-week cluster period and a conventional 12-week schedule during the incremental-dose phase. METHODS: Of 239 patients with rhinitis, allergic bronchial asthma, or both caused by D pteronyssinus , 120 were randomly assigned to the cluster schedule, and 119 were randomly assigned to the conventional schedule. A biologically standardized D pteronyssinus depot extract (ALK-Abelló S.A., Madrid, Spain) was administered in a placebo-controlled, double-blind fashion during the initial phase of cluster or conventional treatment. We recorded adverse reactions, clinical efficacy, cutaneous reactivity, and serum specific immunoglobulins to D pteronyssinus before immunotherapy, when the maximum dose was reached in the cluster and conventional schedules, and after 1 year of treatment. RESULTS: The cluster schedule reduced the time to maintenance dose by 46% and caused systemic adverse reactions (all mild) after only 0.15% of injections, with no differences in comparison with the conventional schedule. Cluster immunotherapy led to decreases in asthma and rhinitis symptoms, reduced the cutaneous reactivity, and produced the increase in specific IgE and IgG 4 levels on reaching the maintenance dose in the sixth week, 6 weeks earlier than with the conventional schedule. CONCLUSION: The cluster schedule for the initial phase of immunotherapy with incremental doses of D pteronyssinus is a safe alternative to conventional immunotherapy and offers the further advantage of achieving clinical and immunologic improvements sooner.