Selection of allergen extract for immunotherapy in polysensitized allergic rhinitis patients.

Aim: To evaluate the criteria used by allergists in selecting an immunotherapy extract (allergen immunotherapy [AIT]-extract) in rhinitis patients with polysensitization. Methods: First, a cross-sectional study was carried out by evaluating different factors that influence the medical choice of AIT-extract. Second, a literature review was performed by evaluating the diagnostic performance of atopy tests. Results: A total of 419 patients were included (84 children, 149 adolescents and 186 adults). Anamnesis, atopy tests and exposure to pets were the main factors for choosing the AIT extract. The sensitivity and specificity of atopy tests were high for Dermatophagoides spp., (>80%), moderate for pets (60%) and indeterminate for Blomia tropicalis. Conclusion: NCTs could be necessary for AIT-extract selection in polysensitized allergic rhinitis patients.

Allergen immunotherapy is an effective treatment for patients with allergic rhinitis. Atopy tests are used to identify possible substances in the environment that cause symptoms. A patient may sometimes have multiple substances which could be causing their allergic reactions, which makes it difficult to choose the appropriate immunotherapy for the patient. In this study, we identified some factors that might help to guide the criteria used by allergists when selecting the extract for immunotherapy.

A human monoclonal antibody based immunoenzymetric assay to measure Fel d 1 concentrations in cat hair and pelt allergenic extracts.

In the United States, 19 allergen extracts of different specificities are standardized, which means that their potencies are determined in comparison to a US reference standard. For cat allergen extracts, potency is determined by measuring Fel d 1 content expressed in in Fel d 1 units, and with a unitage that correlates with skin test reactions (bioequivalent allergy units or BAU). Currently, Fel d 1 content is measured with a radial immunodiffusion (RID) assay that uses polyclonal sheep antisera to detect the allergenic protein by producing a white precipitin line in agar gel. However, the RID is considered cumbersome, and the polyclonal sera may qualitatively vary among animals and may recognize epitopes irrelevant to human allergic disease. In this report, we describe a quantitative two-site immunoenzymetric assay (IEMA) for Fel d 1 that uses immobilized capture and soluble biotin-labeled detection Fel d 1-specific human IgE monoclonal antibodies (mAb) that have been class-switched to IgG4. Together, they sandwich Fel d 1 molecules from extracts. Using purified natural Fel d 1 as a calibrator, the historically reported ∼4 micrograms Fel d 1/Fel d 1 unit assignment was directly measured in this mAb-based IEMA at 3.12 ± 0.24 micrograms of Fel d 1 per Fel d 1 unit. This IEMA appears to be equivalent to RID in the measurement of biological potencies of commercial cat hair and cat pelt extracts marketed in the United States.

The Potential of Human Monoclonal IgE Antibodies to Establish Biological Potency and Stability of Allergen Extracts.

PURPOSE OF REVIEW: Allergenic extracts are often standardized to control for potency, either by measuring concentrations of major allergens or "overall allergenicity" by competition for IgE in pooled sera from highly allergic subjects with a reference extract. Recent developments present an opportunity to use human mAb cloned from highly allergic subjects to define potency of allergenic extracts. RECENT FINDINGS: Two recent developments present an opportunity for revising potency measurements of allergen extracts: cloning allergen specific IgE from allergic subjects and extensive epitope mapping of major allergenic proteins. Because human IgE mAb recognize biologically relevant epitopes, they present a novel opportunity to determine the potencies of allergenic extracts and may contribute to the science base for allergen standardization.

Novel monoclonal antibodies against house dust mite allergen Der p 21 and their application to analyze allergen extracts.

Background: Allergen extracts and recombinant allergens are used in allergy diagnostics and immunotherapy. Since allergen extracts from different manufacturers lack proper standardization regarding their composition, monoclonal antibodies (MAbs) against specific allergen components can be used for their identification and quantification in allergen extracts. This study aimed to generate MAbs against allergen Der p 21 of Dermatophagoides pteronyssinus for the analysis of allergen extracts. Methods: Recombinant Der p 21 was expressed in E. coli and purified using affinity chromatography. MAbs against Der p 21 were generated using hybridoma technology. House dust mite (HDM) allergen extracts were analyzed using the newly developed sandwich enzyme-linked immunosorbent assay, Western blotting and microarray immunoassay. Results: MAbs raised against recombinant Der p 21 were characterized in detail and proven to be reactive with natural Der p 21. Highly specific sandwich enzyme-linked immunosorbent assay for the quantification of Der p 21 was developed and optimized. The allergen was detected and its concentration was determined in only three of six analyzed HDM allergen extracts from different manufacturers. Conclusion: HDM analysis by MAb-based immunoassays shows their differences in allergen composition. The results demonstrate the importance of allergen-specific MAbs as a tool for the characterization of allergen extracts and the need for their appropriate standardization before their use for allergy diagnostics or immunotherapy.

NOVEOS and ImmunoCAP Have Similar Performances for Diagnosing Food Allergies.

BACKGROUND: The clinical significance of newly available platforms for specific IgE measurement must be evaluated. However, data are lacking for NOVEOS (Hycor), especially for food allergens. OBJECTIVE: We compared the technical and clinical performance of two platforms (ImmunoCAP and NOVEOS) to measure specific IgE to 10 food allergens. METHODS: Sera from 289 clinically characterized patients were tested for IgE specific for six food allergen extracts (egg white, cow's milk, peanut, hazelnut, fish, and shrimp) and four molecular allergens (Gal d 1, Bos d 8, Ara h 2, and Cor a 14). Specific IgE measurements were carried out using ImmunoCAP and NOVEOS methods. Food allergy diagnoses were established according to international guidelines. RESULTS: A strong correlation (ρ > 0.9) was present between the two platforms whereas specific IgE concentrations measured with NOVEOS were consistently lower (mean, -15%) than with ImmunoCAP. NOVEOS and ImmunoCAP provided similar overall odds ratios and relative risks for food allergy diagnosis with both allergen extracts and molecular allergens. When all 10 allergens were considered, NOVEOS provided better receiver operating characteristic curves (P = .04). Finally, we found that the most discordant results were observed with hazelnut and peanut extracts and were related to cross-reactive carbohydrate determinants for these two with ImmunoCAP. CONCLUSIONS: Specific IgE determination by either ImmunoCAP or NOVEOS (odds ratios of allergy, 25.1 or 33.0, respectively) is highly informative regarding the risk of allergy in the selected population. The NOVEOS platform presents the advantage of being less affected by unwanted reactivity owing to carbohydrate determinant-specific IgE while requiring a 10-fold lower test sample volume.

Selected Technical Aspects of Molecular Allergy Diagnostics.

Diagnosis of allergic diseases is a complex, multi-stage process. It often requires the use of various diagnostic tools. The in vitro diagnostics (IVD), which includes various laboratory tests, is one of the stages of this process. Standard laboratory tests include the measurement of the serum concentration of specific immunoglobulin E (sIgE) for selected allergens, full allergen extracts and/or single allergen components (molecules). The measurement of IgE sIgE to the allergen components is called molecular allergy diagnosis. During the standard laboratory diagnostic process, various models of immunochemical tests are used, which enable the measurement of sIgE for single allergens (one-parameter tests, singleplex) or IgE specific for many different allergens (multi-parameter tests, multiplex) in one test. Currently, there are many different test kits available, validated for IVD, which differ in the method type and allergen profile. The aim of the manuscript is to present various technical aspects related to modern allergy diagnostics, especially in the area of molecular allergy diagnostics.

Development of gastro-food allergy model in shrimp allergen extract-induced sensitized mice promotes mast cell degranulation.

Background: Food allergies have become more common in the last decade. Shrimp is one of the most dominant food allergy triggers in Asian countries, including Indonesia. After ingesting allergens, B cells will produce allergen-specific Immunoglobin E (IgE). In the sensitization period, repeated allergen exposure promotes Mast Cell (MC) degranulation in intestinal tissue and releases several inflammatory mediators, thereby causing hypersensitivity reactions. Shrimp Allergen Extract (SAE) is an immunotherapy and diagnostic agent currently being developed in Indonesia. In this study, we investigated the effect of SAE administration on eliciting an MC immunological response. Methods: Mice were divided into a non-sensitized and sensitized group. The non-sensitized group only received 1 mg of alum (i.p), whereas the sensitized group received 1 mg of alum and 100 µg of SAE on days 0, 7, and 14. Then, both groups were challenged with 400 µg SAE (p.o) on days 21, 22, and 23 following systemic allergic symptom observation. Results: We showed that SAE was able to increase systemic allergic symptoms significantly in the sensitized mice through repeated challenge (1.33±0.21; 1.83±0.17; and 2.00±0.00), compared to non-sensitized mice (0.17±0.17). Moreover, histopathological analysis showed that the SAE administration causes an increase of MC degranulation in the ileum tissue of the sensitized mice (44.43%±0.01), compared to non-sensitized mice (35.45%±0.01). Conclusions: This study found that SAE could induce allergic reactions in mice by influencing critical effector cells, MCs.

International consensus statement on allergy and rhinology: Allergic rhinitis - 2023.

BACKGROUND: In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence-based findings and recommendation from the full document. METHODS: ICAR-Allergic Rhinitis 2023 employed established evidence-based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work. RESULTS: ICAR-Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost. CONCLUSION: The ICAR-Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment.

Component-Resolved Diagnosis Based on a Recombinant Variant of Mus m 1 Lipocalin Allergen.

Exposure to the Mus m 1 aeroallergen is a significant risk factor for laboratory animal allergy. This allergen, primarily expressed in mouse urine where it is characterized by a marked and dynamic polymorphism, is also present in epithelium and dander. Considering the relevance of sequence/structure assessment in protein antigenic reactivity, we compared the sequence of the variant Mus m 1.0102 to other members of the Mus m 1 allergen, and used Discotope 2.0 to predict conformational epitopes based on its 3D-structure. Conventional diagnosis of mouse allergy is based on serum IgE testing, using an epithelial extract as the antigen source. Given the heterogeneous and variable composition of extracts, we developed an indirect ELISA assay based on the recombinant component Mus m 1.0102. The assay performed with adequate precision and reasonable diagnostic accuracy (AUC = 0.87) compared to a routine clinical diagnostic test that exploits the native allergen. Recombinant Mus m 1.0102 turned out to be a valuable tool to study the fine epitope mapping of specific IgE reactivity to the major allergen responsible for mouse allergy. We believe that advancing in its functional characterization will lead to the standardization of murine lipocalins and to the development of allergen-specific immunotherapy.

Guideline on allergen immunotherapy in IgE-mediated allergic diseases: S2K Guideline of the German Society of Allergology and Clinical Immunology (DGAKI), Society of Pediatric Allergology and Environmental Medicine (GPA), Medical Association of German Allergologists (AeDA), Austrian Society of Allergology and Immunology (ÖGAI), Swiss Society for Allergology and Immunology (SSAI), German Dermatological Society (DDG), German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNO-KHC), German Society of Pediatrics and Adolescent Medicine (DGKJ), Society of Pediatric Pulmonology (GPP), German Respiratory Society (DGP), German Professional Association of Otolaryngologists (BVHNO), German Association of Paediatric and Adolescent Care Specialists (BVKJ), Federal Association of Pneumologists, Sleep and Respiratory Physicians (BdP), Professional Association of German Dermatologists (BVDD).

Not available.

Immunotherapies in the treatment of immunoglobulin E­mediated allergy: Challenges and scope for innovation (Review).

Immunoglobulin E (IgE)­mediated allergy or hypersensitivity reactions are generally defined as an unwanted severe symptomatic immunological reaction that occurs due to shattered or untrained peripheral tolerance of the immune system. Allergen­specific immunotherapy (AIT) is the only therapeutic strategy that can provide a longer­lasting symptomatic and clinical break from medications in IgE­mediated allergy. Immunotherapies against allergic diseases comprise a successive increasing dose of allergen, which helps in developing the immune tolerance against the allergen. AITs exerttheirspecial effectiveness directly or indirectly by modulating the regulator and effector components of the immune system. The number of success stories of AIT is still limited and it canoccasionallyhave a severe treatment­associated adverse effect on patients. Therefore, the formulation used for AIT should be appropriate and effective. The present review describes the chronological evolution of AIT, and provides a comparative account of the merits and demerits of different AITs by keeping in focus the critical guiding factors, such as sustained allergen tolerance, duration of AIT, probability of mild to severe allergic reactions and dose of allergen required to effectuate an effective AIT. The mechanisms by which regulatory T cells suppress allergen­specific effector T cells and how loss of natural tolerance against innocuous proteins induces allergy are reviewed. The present review highlights the major AIT bottlenecks and the importantregulatory requirements for standardized AIT formulations. Furthermore, the present reviewcalls attention to the problem of 'polyallergy', which is still a major challenge for AIT and the emerging concept of 'component­resolved diagnosis' (CRD) to address the issue. Finally, a prospective strategy for upgrading CRD to the next dimension is provided, and a potential technology for delivering thoroughly standardized AIT with minimal risk is discussed.

Preparation of chemically stable allergen-specific sublingual immunotherapy from Egyptian allergens.

BACKGROUND: The term "allergen extracts" refers to solutions of proteins or glycoproteins extracted from source raw materials. OBJECTIVES: This study was planned to prepare chemically stable sublingual immunotherapy from different allergens in Egypt. METHODS: Allergen extraction from raw materials. The concentrated aqueous extract of each allergen was mixed with an equal volume of glycerol. The protein content of the preparations was determined using the modified Lowry assay method. The prepared allergens were stored for 9 months at 2-4°C. Samples were analyzed periodically (0, 3, 6, and 9 months of intervals) adopting the Lowry Assay method. Levels of specific IgE to Chenopodium album antigens were measured in patients' sera by ELISA. RESULTS: The concentration of all prepared allergens, as indicated by the concentration of the protein content, was found to decrease exponentially with time, implying first-order kinetics of degradation. From the values of the slopes of the log plot for each allergen, the half-life time (t1/2 ) and (t1/4 ) values were calculated. The expiration date was considered as the time after which the allergen loses 25% of its potency. The obtained values of t1/4% vary according to the type of vaccine. The most stable one is that of Chenopodium album pollens (2.4 years) and the least stable is that of house dust Mites (9 months). The immunological characters of Chenopodium album extract were stable for at least 6 months. CONCLUSION: Differences exist among allergen extracts made by multiple manufacturers. So, developments in studies on allergen preparation and characterization in a different locality are necessary.

Allergen Immunotherapy Extract Shortages and Their Effects on Clinical Care: A Work Group Report of the AAAAI Immunotherapy, Allergen Standardization, and Allergy Diagnostics Committee.

Allergen immunotherapy (AIT) is the only disease-modifying therapy indicated for treatment of allergic asthma, rhinitis, conjunctivitis, and Hymenoptera hypersensitivity. Manufacturing of the extracts used in AIT involve multistep complex processes as well as regulatory oversight. Furthermore, some source materials are vulnerable to unexpected events of nature. Given these circumstances, allergen extract supply can be disrupted with a potential to adversely impact patient care. A group of members from the American Academy of Allergy, Asthma, and Immunology (AAAAI) Immunotherapy, Allergy Standardization and Allergy Diagnostic Committee formed a workgroup to assess the frequency and effects of allergen extract shortages and associated factors. This workgroup developed a survey that was distributed to a random 20% of the AAAAI membership. In addition, the group also performed a review of the scientific literature on allergen extract supply and shortage. Based on the findings of the survey study and literature review, the workgroup reports frequency and extent of shortages, potential ways to improve communication with suppliers, and need for further guidance in patient care during times of shortage.

Immunological effects of adjuvanted low-dose allergoid allergen-specific immunotherapy in experimental murine house dust mite allergy.

BACKGROUND: Native allergen extracts or chemically modified allergoids are routinely used to induce allergen tolerance in allergen-specific immunotherapy (AIT), although mechanistic side-by-side studies are rare. It is paramount to balance optimal dose and allergenicity to achieve efficacy warranting safety. AIT safety and efficacy could be addressed by allergen dose reduction and/or use of allergoids and immunostimulatory adjuvants, respectively. In this study, immunological effects of experimental house dust mite (HDM) AIT were investigated applying high-dose HDM extract and low-dose HDM allergoids with and without the adjuvants microcrystalline tyrosine (MCT) and monophosphoryl lipid A (MPL) in a murine model of HDM allergy. METHODS: Cellular, humoral, and clinical effects of the different AIT strategies were assessed applying a new experimental AIT model of murine allergic asthma based on physiological, adjuvant-free intranasal sensitization followed by subcutaneous AIT. RESULTS: While low-dose allergoid and high-dose extract AIT demonstrated comparable potency to suppress allergic airway inflammation and Th2-type cytokine secretion of lung-resident lymphocytes and draining lymph node cells, low-dose allergoid AIT was less effective in inducing a potentially protective IgG1 response. Combining low-dose allergoid AIT with MCT or MCT and dose-adjusted MPL promoted Th1-inducing mechanisms and robust B-cell activation counterbalancing the allergic Th2 immune response. CONCLUSION: Low allergen doses induce cellular and humoral mechanisms counteracting Th2-driven inflammation by using allergoids and dose-adjusted adjuvants. In light of safety and efficacy improvement, future therapeutic approaches may use low-dose allergoid strategies to drive cellular tolerance and adjuvants to modulate humoral responses.

The Effect of Broccoli Sprout Extract on Seasonal Grass Pollen-Induced Allergic Rhinitis.

Patients exposed to pollutants are more likely to suffer from allergic rhinitis and may benefit from antioxidant treatment. Our study determined if patients diagnosed with grass-induced allergic rhinitis could benefit from broccoli sprout extract (BSE) supplementation. In total, 47 patients were confirmed with grass-induced allergic rhinitis and randomized to one of four groups: group 1 (nasal steroid spray + BSE), group 2 (nasal steroid spray + placebo tablet), group 3 (saline nasal spray + BSE) and group 4 (saline nasal spray + placebo tablet). Peak Nasal Inspiratory Flow (PNIF), Total Nasal Symptoms Scores (TNSS) and nasal mucus cytokine levels were analyzed in samples collected before and after the 3-week intervention. Comparing before and after the intervention, PNIF improved significantly when comparing Groups 1 and 2, vs. placebo, at various time points (p ≤ 0.05 at 5, 15, 60 and 240 min) following nasal challenge, while TNSS was only statistically significant at 5 (p = 0.03), 15 (p = 0.057) and 30 (p = 0.05) minutes. There were no statistically significant differences in various cytokine markers before and after the intervention. Combining nasal corticosteroid with BSE led to the most significant improvement in objective measures.

Safety of semi-depot house dust mite allergen extract in children and adolescents with allergic rhinitis and asthma.

Aim: Multicenter study to investigate the safety of mite extract product Novo-Helisen Depot, Strengths 1 to 3 (NHD3), as subcutaneous immunotherapy (SCIT), in Chinese children and adolescents with allergic rhinitis (AR) and allergic asthma (AA). Patients & methods: We evaluated SCIT-related adverse events (AEs) during NHD3 14-week initial therapy in children (5-11 years) and adolescents (12-17 years) with perennial symptomatic AR and AA. Results: Among 3600 injections in 250 patients, 361/3600 (10.0%) injections caused SCIT-related AEs in 96/250 (38.4%) patients, 321/3600 injections (8.9%) caused local reactions in 89/250 (35.6%) and 40/3600 injections (1.1%) caused systemic reactions in 23/250 (9.2%). Conclusion: Initial SCIT treatment using NHD3 was safe and well tolerated in Chinese children and adolescents with AR and AA.

Compromising between European and US allergen immunotherapy schools: Discussions from GUIMIT, the Mexican immunotherapy guidelines.

BACKGROUND: Allergen immunotherapy (AIT) has a longstanding history and still remains the only disease-changing treatment for allergic rhinitis and asthma. Over the years 2 different schools have developed their strategies: the United States (US) and the European. Allergen extracts available in these regions are adapted to local practice. In other parts of the world, extracts from both regions and local ones are commercialized, as in Mexico. Here, local experts developed a national AIT guideline (GUIMIT 2019) searching for compromises between both schools. METHODS: Using ADAPTE methodology for transculturizing guidelines and AGREE-II for evaluating guideline quality, GUIMIT selected 3 high-quality Main Reference Guidelines (MRGs): the European Academy of Allergy, Asthma and Immunology (EAACI) guideines, the S2k guideline of various German-speaking medical societies (2014), and the US Practice Parameters on Allergen Immunotherapy 2011. We formulated clinical questions and based responses on the fused evidence available in the MRGs, combined with local possibilities, patient's preference, and costs. We came across several issues on which the MRGs disagreed. These are presented here along with arguments of GUIMIT members to resolve them. GUIMIT (for a complete English version, Supplementary data) concluded the following. RESULTS: Related to the diagnosis of IgE-mediated respiratory allergy, apart from skin prick testing complementary tests (challenges, in vitro testing and molecular such as species-specific allergens) might be useful in selected cases to inform AIT composition. AIT is indicated in allergic rhinitis and suggested in allergic asthma (once controlled) and IgE-mediated atopic dermatitis. Concerning the correct subcutaneous AIT dose for compounding vials according to the US school: dosing tables and formula are given; up to 4 non-related allergens can be mixed, refraining from mixing high with low protease extracts. When using European extracts: the manufacturer's indications should be followed; in multi-allergic patients 2 simultaneous injections can be given (100% consensus); mixing is discouraged. In Mexico only allergoid tablets are available; based on doses used in all sublingual immunotherapy (SLIT) publications referenced in MRGs, GUIMIT suggests a probable effective dose related to subcutaneous immunotherapy (SCIT) might be: 50-200% of the monthly SCIT dose given daily, maximum mixing 4 allergens. Also, a table with practical suggestions on non-evidence-existing issues, developed with a simplified Delphi method, is added. Finally, dissemination and implementation of guidelines is briefly discussed, explaining how we used online tools for this in Mexico. CONCLUSIONS: Countries where European and American AIT extracts are available should adjust AIT according to which school is followed.

Basophil Activation Test Based on CD203c Expression in the Diagnosis of Fish Allergy.

PURPOSE: The basophil activation test (BAT) has been reported to be useful for the diagnosis of various food allergies, such as allergy to peanut, but not to fish. This study aimed to evaluate the diagnostic performance of the BAT for fish allergy. METHODS: We performed a retrospective review of patients with fish allergy who underwent the BAT using a panel of fish extracts (15 kinds) to examine the differential reactivity to several species of fish. The BAT score for each extract was expressed as the ratio of CD203chigh% with the extract to that with anti-IgE antibody. Clinical reactivity to each fish was confirmed by positive oral food challenge or a typical history of fish-induced immediate allergy symptoms. Receiver-operating-characteristic (ROC) analysis was performed to evaluate the diagnostic performance. RESULTS: Fifty-one patients with fish allergy were analyzed. Using extracts of 15 species of fish, the BAT was performed a total of 184 times on the patients. Clinical allergy to each species of fish was confirmed in 90 (48.9%) of those tests. ROC analysis yielded high areas under the curve for the BAT scores for the 5 most common fish species (0.72-0.88). The diagnostic accuracy ranged from 0.74 to 0.86. Using a tentative cutoff value of 0.3 deduced from the ROC analyses of the 5 fish species, the accuracy for other fish allergic reactions was generally high (0.6-1.0), except the fish tested in a small number of patients. CONCLUSIONS: The BAT score based on CD203c expression may be useful for fish allergy diagnosis, especially since a large variety of fish can be tested by the BAT using fish extracts prepared by a simple method.

Subcutaneous allergen immunotherapy for asthma: A randomized, double-blind, placebo-controlled study with a standardized Blomia tropicalis vaccine.

BACKGROUND: Sensitization to Blomia tropicalis (Bt) is very frequent in the tropics, and particularly in Cuba, being a significant cause of allergic asthma. Allergen immunotherapy (AIT) with Bt can be a therapeutic option, however, placebo-controlled clinical trials have not been reported. OBJECTIVE: To assess the therapeutic effect and safety of AIT for asthma using a standardized allergen vaccine of B. tropicalis by subcutaneous route, in allergic asthmatic patients exposed and sensitized to this mite species. METHODS: A double-blind, placebo-controlled Phase II trial was conducted in 35 adults (18 with treatment and 17 with placebo), with mild to moderate asthma, predominantly sensitized to Bt. AIT was administered subcutaneously in increasing doses from 4 to 6000 Biological Units using a locally manufactured standardized extract (BIOCEN, Cuba). Patient assessment was performed using symptom-medication score (SMS), peak expiratory flow and skin reactivity relative to Histamine as measured by skin prick test (SPT). RESULTS: The 12-month treatment achieved a significant (p < 0.001) decrease of SMS. Symptom score showed only 41% (CI: 26-61) of placebo values, whereas medication was 34.5% (22.4%-63.3%). Treatment was regarded clinically effective in 67% of patients (OR 32; 95%CI: 17 to 102). The effect size on symptoms and medication was higher than has been reported with equivalent allergen dosages of D. pteronyssinus and D. siboney in Cuban asthmatic patients. Skin reactivity to Bt was also significantly reduced (p = 0.0001), increasing 148-fold the allergen threshold to elicit a positive skin test. This desensitization effect was specific to Bt and did not modify the reactivity to Dermatophagoides. The change of specific skin reactivity was significantly (p < 0.05) correlated to clinical improvement. All adverse events were local with a frequency of 2.4% of injections. CONCLUSIONS: Subcutaneous AIT with Blomia tropicalis was effective and safe in asthmatic adults exposed and sensitized to this mite species in a tropical environment. TRIAL REGISTRATION: Cuban Public Registry of Clinical Trials: RPCEC00000026 (WHO International Clinical Trial Registry Platform ICTRP).