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Summary: Background. Local Allergic Rhinitis (LAR) is a phenotype defined by rhinitis symptoms with negative responses to systemic sensitization tests but with an exclusively nasal allergic inflammatory response. Data on the pediatric age group is scarce, and no Latin American data has been published so far. Methods. Nasal Allergen Challenge (NAC) was performed with Dermatophagoides pteronyssinus and Blomia tropicalis in six- to 18-year-old patients diagnosed with rhinitis and no systemic sensitization. NAC was monitored using subjective parameters and acoustic rhinometry. The study aimed to identify LAR in child and adolescent subjects previously diagnosed with non-allergic rhinitis (NAR) in a Brazilian specialty outpatient clinic (Allergy and Immunology). Results. During the study period, we analyzed 758 skin prick tests (SPT). Of those, 517 (68.2%) were diagnosed with rhinitis. Among those, 18.4% (95/517) had a negative SPT, meeting the criteria for inclusion in the study. Twenty-five patients underwent NAC, and 40% (10/25) of them, previously considered to have NAR, had a positive test and were reclassified as having LAR. Based on the analyzed characteristics, clinically differentiating LAR from NAR was impossible. Conclusions. This study represents the first investigation of LAR in child and adolescent subjects in Latin America, contributing significantly to the understanding of its prevalence and characteristics in this geographic area. Among a subgroup of patients lacking systemic sensitization submitted to NAC, 40% (10/25) demonstrated a positive NAC with Dermatophagoides pteronyssinus and Blomia tropicalis, warranting their reclassification to LAR. NAC with multiple allergens has been proven safe and viable in pediatric populations, affirming its critical role in the accurate diagnosis of LAR.
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BACKGROUND: There is a lack of information on house dust mite (HDM) sensitization and phenotype distribution in patients with severe asthma (SA) living permanently at high-altitude (HA) in tropical regions, which may be different. OBJECTIVE: The aim of this study was to characterize adults with SA in a tropical high altitude city (2,640 m): Bogotá, Colombia. MATERIAL AND METHODS: This observational cross-sectional study included severe asthmatic outpatients (n = 129) referred to the ASMAIRE program of the Fundación Neumológica Colombiana in Bogotá (2,640 m). Clinical history, spirometry, total IgE, blood eosinophils, and skin prick test (SPT), including HDM allergens, were performed. Phenotype definitions: Allergic/atopic (AA): IgE ≥100 IU/mL and/or at least one positive SPT; eosinophilic (EOS): blood eosinophils ≥300 cells/µL; type 2-high: AA and/or EOS phenotype; type 2-low: non-AA/non-EOS phenotype (IgE <100 IU/mL, negative SPT, and blood eosinophils <300 cells/µL). RESULTS: A total of 129 adults with SA were included, 79.8% female. Phenotype distribution: AA: 61.2%; EOS: 37.2%; type 2-high: 72.1%; type 2-low: 27.9%. Among AA patients, HDM sensitization was present in 87% and 34.9% were non-eosinophilic. There was a significant overlap between the phenotypes. CONCLUSIONS: In contrast to non-tropical high-altitude regions, we found a high frequency of HDM sensitization in patients with AA phenotype living in a tropical high-altitude city. We also found a discrete lower frequency of EOS phenotype with no other significant differences in the phenotypic distribution compared to that described at low altitudes. We propose that tropical location may modify the effect of high altitude on HDM concentrations and allergenicity.
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Asma , Hipersensibilidade , Humanos , Adulto , Animais , Feminino , Masculino , Asma/epidemiologia , Pyroglyphidae , Altitude , Imunoglobulina E , Dermatophagoides pteronyssinus , Alérgenos , Testes Cutâneos , Antígenos de Dermatophagoides , PoeiraRESUMO
Macrophage migration inhibitory factor (MIF) is present in high amounts in the BALF and serum of asthmatic patients, contributing to the pathogenesis of experimental asthma induced by OVA in mice. Whether MIF contributes to the physiopathology on a more complex and relevant asthma model has not been characterized. Mif-deficient (Mif-/- ) or WT mice treated with anti-MIF antibody were challenged multiple times using house dust mite (HDM) extract by the intranasal route. HDM-challenged Mif-/- mice presented decreased airway hyperresponsiveness, lung infiltration of eosinophils, mucus hypersecretion, and subepithelial fibrosis compared to HDM-challenged WT mice. Amounts of IL-4, IL-5, and IL-13 were decreased in the lungs of Mif-/- mice upon HDM challenges, but the increase of CCL11 was preserved, compared to HDM-challenged WT mice. We also observed increased numbers of group 2 innate lymphoid cells and Th2 cells in the BALF and mediastinal LNs (mLN)-induced challenged by HDM of WT mice, but not in HDM-challenged Mif-/- mice. Anti-MIF treatment abrogated the airway infiltration of eosinophils, mucus hypersecretion, and subepithelial fibrosis in the lungs of HDM-challenged mice. In conclusion, MIF ablation prevents the pathologic hallmarks of asthma in HDM-challenged mice, reinforcing the promising target of MIF for asthma therapy.
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Asma , Fatores Inibidores da Migração de Macrófagos , Animais , Camundongos , Pyroglyphidae , Fatores Inibidores da Migração de Macrófagos/genética , Imunidade Inata , Linfócitos/patologia , Pulmão , Inflamação/patologia , FibroseRESUMO
Background: Allergen Immunotherapy (AIT) represents one of the pillars in the treatment of allergic diseases. AIT is the only therapeutic strategy with curative potential, promoting the reduction of drug use and long-term symptom control even after the end of the treatment. The European Academy of Allergy, Asthma and Immunology (EAACI) guidelines, position papers of World Allergy Organization (WAO), and the US Practice Parameters are the leading official documents that set scientific standard for the use of AIT in the world. The use of AIT in Brazil has specific regional conditions due to the pattern of allergen sensitization, as well as genetic, socioeconomic, and cultural characteristics, climate conditions, and the availability of allergenic extracts. The most prevalent house dust mites are Dermatophagoides pteronyssinus, Dermatophagoides farinae and their allergens have the highest clinical relevance. Blomia tropicalis is also very frequent. This position paper has been prepared by the Brazilian Association of Allergy and Clinical Immunology (ASBAI) Taskforce on AIT for respiratory allergy and Hymenoptera venom allergy. Objective: According to the current scientific literature adapted to the Brazilian reality, this position paper aims to establish the main recommendations for the good clinical practice parameters for AIT in Brazil. Methods: A systematic review using the Pub Med and Cochrane databases was performed, and the websites of major allergy and immunology organizations were consulted. The research was limited to English language literature and was conducted between March 30, 2002, and March 30, 2022. The terms used for the research were: Allergen Immunotherapy, sublingual immunotherapy (SLIT), subcutaneous immunotherapy (SCIT), venom-specific immunotherapy (VIT), and allergen extract. Results: The several recommendations that establish the clinical practices for AIT recommended by the main Allergy, Asthma and Immunology world organizations were analyzed and adapted to the Brazilian situation. Conclusion: This position paper establishes the main recommendations for the effective clinical practice of AIT in Brazil, using current knowledge of evidence-based medicine and precision medicine.
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BACKGROUND: Patients with allergic rhinitis to house dust mites have an increased risk of shrimp allergy. Der p 10 is a candidate biomarker to predict the risk of shrimp allergy among allergic rhinitis patients. OBJECTIVES: The aim of this study was to evaluate the diagnostic performance of anti-Der p 10 IgE as a predictor of shrimp allergy. METHODS: A nested case-control study was carried out with eighty-six allergic rhinitis patients sensitized to mite (Dermatophagoides pteronyssinus) and shrimp (Litopenaeu vannamei). Cases and controls were defined by anti-Der p 10 IgE results. Oral challenge with shrimp was used as the gold standard for the evaluation of diagnostic performance. RESULTS: All shrimp oral challenge test (OCT)-positive patients were positive for IgE against Der p 10. The level of anti-Der p 10 IgE >1.2 kUA/mL had the best diagnostic performance (sensitivity 100%, specificity 65%) Conclusion: Anti-Der p 10 IgE is useful for predicting shrimp allergy diagnosis and could reduce the requirement of an OCT.
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Imunoglobulina E , Rinite Alérgica , Alérgenos , Animais , Antígenos de Dermatophagoides , Estudos de Casos e Controles , Crustáceos , Humanos , Pyroglyphidae , Rinite Alérgica/diagnósticoRESUMO
Airway obstruction with increased airway resistance in asthma, commonly caused by smooth muscle constriction, mucosal edema and fluid secretion into the airway lumen, may partly be due to a poor function of pulmonary surfactant. Surfacen®, a clinical pulmonary surfactant, has anti-inflammatory action, but its effect on asthma has not been studied. This work aimed to evaluate the effect of Surfacen® in a murine allergen-induced acute asthma model, using house dust mite allergens. In a therapeutic experimental setting, mice were first sensitized by being administered with two doses (sc) of Dermatophagoides siboney allergen in aluminum hydroxide followed by one intranasal administration of the allergen. Then, sensitized mice were administered with aerosol of hypertonic 3% NaCl, Salbutamol 0.15 mg/kg, or Surfacen® 16 mg in a whole-body chamber on days 22, 23, and 24. Further, mice were subjected to aerosol allergen challenge on day 25. Surfacen® showed bronchial dilation and inhibition of Th2 inflammation (lower levels of IL-5 and IL-13 in broncoalveolar lavage) which increased IFN-γ and unchanged IL-10 in BAL. Moreover, Sufacen® administration was associated with a marked inhibition of the serum specific IgE burst upon allergen exposure, as well as, IgG2a antibody increase, suggesting potential anti-allergy effects with inclination towards Th1. These results support also the effectiveness of the aerosol administration method to deliver the drug into lungs. Surfacen® induced a favorable pharmacological effect, with a bronchodilator outcome comparable to Salbutamol, consistent with its action as a lung surfactant, and with an advantageous anti-inflammatory and anti-allergic immunomodulatory effect.
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Antialérgicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Fosfolipídeos/uso terapêutico , Proteínas Associadas a Surfactantes Pulmonares/uso terapêutico , Alérgenos/imunologia , Animais , Antígenos de Dermatophagoides/imunologia , Asma/sangue , Asma/imunologia , Asma/patologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Camundongos Endogâmicos BALB CRESUMO
BACKGROUND: Sensitization to house dust mites (HDMs) is frequent in patients with atopic dermatitis. OBJECTIVE: To investigate the efficacy of sublingual immunotherapy (SLIT) with Dermatophagoides pteronyssinus extract in patients with atopic dermatitis sensitized to HDM. METHODS: In this randomized, double-blind, placebo-controlled trial, we enrolled 91 patients 3 years or older, with SCORing Atopic Dermatitis (SCORAD) score greater than or equal to 15 and positive skin test result and/or IgE to D pteronyssinus. Patients were stratified according to age (<12 and ≥12 years) to receive HDM SLIT or placebo for 18 months. Primary outcome was a greater than or equal to 15-point decrease in SCORAD score. Secondary outcomes were decreases in SCORAD and objective SCORAD, Eczema Area and Severity Index, visual analog scale for symptoms, and pruritus scale scores; Investigator's Global Assessment 0/1; and decrease greater than or equal to 4 points in Dermatology Life Quality Index. Background therapy was maintained. RESULTS: A total of 66 patients completed the study (35 HDM SLIT, 31 placebo). After 18 months, 74.2% and 58% of patients in the HDM SLIT group and the placebo group, respectively, showed greater than or equal to 15-point decrease in SCORAD score (relative risk, 1.28; 95% CI, 0.89-1.83). Significant SCORAD score decreases from baseline of 55.6% and 34.5% in HDM SLIT and placebo groups (mean difference, 20.4; 95% CI, 3.89-37.3), significant objective SCORAD score decreases of 56.8% and 34.9% in HDM SLIT and placebo groups (mean difference, 21.3; 95% CI, 0.66-41.81), and more patients with Investigator's Global Assessment 0/1 in the HDM SLIT group as compared with the placebo group (14 of 35 vs 5 of 31; relative risk, 2.63; 95% CI, 1.09-6.39) were observed at 18 months. CONCLUSIONS: Our results suggest that HDM SLIT may be effective in HDM-sensitized patients as an add-on treatment for atopic dermatitis.
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Dermatite Atópica , Eczema , Imunoterapia Sublingual , Animais , Antígenos de Dermatophagoides/uso terapêutico , Criança , Dermatite Atópica/tratamento farmacológico , Dermatophagoides pteronyssinus , Método Duplo-Cego , Eczema/tratamento farmacológico , Humanos , Pyroglyphidae , Imunoterapia Sublingual/métodos , Resultado do TratamentoRESUMO
INTRODUCTION: Cross-reactivity between shrimp and house dust mite (HDM) proteins has been widely documented. In tropical region, shrimp (5-15%) and mite sensitization (80-95%) is prevalent in allergic patients. However, the clinical relevance of shrimp sensitization in patients with allergic rhinitis (AR) has been poorly studied. The aim of this study was to determine the prevalence and the clinical relevance shrimp IgE sensitization in AR patients sensitized to Dermatophagoides pteronyssinus. METHODS: The study was conducted in Medellin (Colombia). A cross-sectional study in patients with AR sensitized to HDM was performed in 3 steps: (i) assessment of IgE sensitization frequency to shrimp Penaeus azteca, Litopenaeus vannamei, and tropomyosin homologous allergens rDer p 10, rPen a 1, and rLit v 1, (ii) evaluation of the clinical relevance of shrimp sensitization using oral challenge test (OCT) and (iii) identification of possible risk factors for positive-OCT results. Ethical committee approval was obtained. RESULTS: From 443 patients with AR, 86 (19.4%) were sensitized to shrimp and 23 of them (26.7%) had shrimp allergy diagnosis. Thirty-six of the patients sensitized to shrimp (41.2%) reported not previously consumed this food and eleven of them had a positive-OCT (30.5%). There was not statistically significant difference in total IgE or sIgE (D. pteronyssinus, P. azteca, L. vannamei, rPen a 1, and rLit v 1) between OCT groups (positive vs. negative results). Anti-Der p 10 IgE was associated with risk for a positive-OCT in different multivariable scenarios. DISCUSSION/CONCLUSION: Our results suggest that in patients with HDM-associated AR and shrimp IgE sensitization is necessary to evaluate the clinical relevance of shrimp IgE even if the patient has never consumed shrimp because of cross-reactivity. Anti-Der p 10 could be a possible biomarker of clinical relevance to shrimp sensitization and could reduce the need for OCTs.
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Antígenos de Dermatophagoides/imunologia , Proteínas de Artrópodes/imunologia , Hipersensibilidade Alimentar/imunologia , Imunoglobulina E/sangue , Penaeidae/imunologia , Rinite Alérgica/imunologia , Tropomiosina/imunologia , Adulto , Alérgenos/imunologia , Animais , Reações Cruzadas , Estudos Transversais , Feminino , Hipersensibilidade Alimentar/sangue , Humanos , Imunoglobulina E/imunologia , Testes Imunológicos , Masculino , Pessoa de Meia-Idade , Rinite Alérgica/sangue , Método Simples-Cego , Adulto JovemRESUMO
Sublingual immunotherapy (SLIT) has been used for more than three decades as a therapeutic strategy for the treatment of allergic diseases. Studies have demonstrated its efficacy and safety, and numerous clinical trials have evaluated these parameters. In the present study, through patient perception, we investigated the patient satisfaction with the use of house dust mite SLIT treatment. "Satisfaction Scale for Patients Receiving Allergen Immunotherapy" (ESPIA) questionnaire, a standardized and validated instrument for clinical studies evaluating allergen immunotherapy, was applied to allergic patients (N = 136). Children and adults of both sexes who received SLIT for Dermatophagoides pteronyssinus and/or Blomia tropicalis, according to the results of an immediate reading puncture test, were included. Data analysis showed that the perception of treatment effectiveness was 92%, performance improvement in the daily activities was 91%, a satisfactory cost-benefit balance was 84%, and the perception of general satisfaction was 97%. The results showed a high perception of satisfaction in allergic patients undergoing house dust mite SLIT.
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Alérgenos/imunologia , Antígenos de Dermatophagoides/imunologia , Hipersensibilidade/terapia , Satisfação do Paciente , Imunoterapia Sublingual , Atividades Cotidianas , Adulto , Animais , Criança , Análise Custo-Benefício , Feminino , Humanos , Hipersensibilidade/economia , Masculino , Pyroglyphidae/imunologia , Testes Cutâneos , Imunoterapia Sublingual/economia , Inquéritos e Questionários , Resultado do TratamentoRESUMO
Successful research in the wide-ranging field of allergy is usually achieved by definition not only of physicochemical and immunological properties of natural, but also recombinant allergens. Blomia tropicalis mite is a well-known source for various groups of hypersensitivity-causing proteins. The goal of the present work was to produce, purify and characterise by in silico, biochemical and immunological methods the recombinant group-12 allergen of B. tropicalis. The recombinant Blo t 12 aggregation capacity as well as the affinity to antibodies from BALB/c immunised mice and B. tropicalis-sensitised human donors were investigated through in silico analyses, dynamic light scattering, SDS-PAGE, ELISA and Western blot. The presence of Blo t 12 within B. tropicalis extracts was also determined by ELISA and Western blot. High concentrations of dimeric rBlo t 12 were detected through SDS-PAGE next to other aggregates and the results were confirmed by data from DLS and Western blot. The YITVM peptide was predicted to be the most aggregation-prone region. The IgE-reactivity of rBlo t 12 was not completely abolished by aggregate formation but it was significantly decreased compared to rBlo t 5, or B. tropicalis extracts. Natural Blo t 12 may naturally dimerises, but it was detected in non-delipidified B. tropicalis extracts in low amounts. Given that this allergen may be a specific marker for B. tropicalis allergy, the recombinant Blo t 12 herein obtained is characterised as a mid-tier allergen in Brazilian atopic patients and may be useful for the improvement in precision allergy molecular diagnostic applications.
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Alérgenos/isolamento & purificação , Ácaros/metabolismo , Alérgenos/genética , Alérgenos/imunologia , Animais , Escherichia coli/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Proteínas RecombinantesRESUMO
Glutathione-S transferases (GSTs) are part of a ubiquitous family of dimeric proteins that participate in detoxification reactions. It has been demonstrated that various GSTs induce allergic reactions in humans: those originating from house dust mites (HDM), cockroaches, and helminths being the best characterized. Evaluation of their allergenic activity suggests that they have a clinical impact. GST allergens belong to different classes: mu (Blo t 8, Der p 8, Der f 8, and Tyr p 8), sigma (Bla g 5 and Asc s 13), or delta (Per a 5). Also, IgE-binding molecules belonging to the pi-class have been discovered in helminths, but they are not officially recognized as allergens. In this review, we describe some aspects of the biology of GST, analyze their allergenic activity, and explore the structural aspects and clinical impact of their cross-reactivity.
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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.
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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).
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INTRODUCTION: Allergen-specific immunotherapy (AIT) represents a curative approach for treating allergies. In the tropical and subtropical regions of the world, Blomia tropicalis (Blo t 5 and Blo t 21) is the likely dominant source of indoor allergens. AIM: To generate a hypoallergenic Blo t 5/Blo t 21 hybrid molecule that can treat allergies caused by B tropicalis. METHODS: Using in silico design of B tropicalis hybrid proteins, we chose two hybrid proteins for heterologous expression. Wild-type Blo t 5/Blo t 21 hybrid molecule and a hypoallergenic version, termed BTH1 and BTH2, respectively, were purified by ion exchange and size exclusion chromatography and characterized by physicochemical, as well as in vitro and in vivo immunological, experiments. RESULTS: BTH1, BTH2 and the parental allergens were purified to homogeneity and characterized in detail. BTH2 displayed the lowest IgE reactivity that induced basophil degranulation using sera from allergic rhinitis and asthmatic patients. BTH2 essentially presented the same endolysosomal degradation pattern as the shortened rBlo t 5 and showed a higher resistance towards degradation than the full-length Blo t 5. In vivo immunization of mice with BTH2 led to the production of IgG antibodies that competed with human IgE for allergen binding. Stimulation of splenocytes from BTH2-immunized mice produced higher levels of IL-10 and decreased secretion of IL-4 and IL-5. In addition, BTH2 stimulated T-cell proliferation in PBMCs isolated from allergic patients, with secretion of higher levels of IL-10 and lower levels of IL-5 and IL-13, when compared to parental allergens. CONCLUSIONS AND CLINICAL RELEVANCE: BTH2 is a promising hybrid vaccine candidate for immunotherapy of Blomia allergy. However, further pre-clinical studies addressing its efficacy and safety are needed.
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Alérgenos , Proteínas de Artrópodes , Hipersensibilidade , Ácaros , Vacinas , Alérgenos/genética , Alérgenos/imunologia , Alérgenos/farmacologia , Animais , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Proteínas de Artrópodes/farmacologia , Citocinas , Feminino , Humanos , Hipersensibilidade/imunologia , Hipersensibilidade/terapia , Masculino , Camundongos Endogâmicos BALB C , Ácaros/genética , Ácaros/imunologia , Vacinas/genética , Vacinas/imunologia , Vacinas/farmacologiaRESUMO
Introduction: Allergic illnesses are one of the most prevalent immunological disorders worldwide and house dust mites are important triggers of these diseases. Allergen-specific immunotherapy (AIT) is an alternative treatment to pharmacotherapy and among its technologies, recombinant hypoallergenic derivatives have shown promising features, turn them into safer and more efficient allergy vaccines.Areas covered: Patents and scientific publications referring to advances in the design of Dermatophagoides spp. hypoallergenic molecules. Data were obtained from the Espacenet® and PubMed websites, using different key terms, advanced tools and Boolean operators for searches. The retrieved data were then descriptively analyzed, taking into consideration clinical targets, geographical, temporal, collaborative, and different classification aspects of the productions.Expert opinion: Joint advances of molecular biology, genetic engineering, and bioinformatics technologies led to progresses in the design of Dermatophagoides spp. hypoallergenic derivatives. Collaborative networks seem to be an interesting way not only to improve technologies in AIT but also to boost the number of patents, publications, and grants for researchers. The observed trend for the use of hypoallergenic hybrid molecules was a fundamental AIT advance and this type of molecule appears to be a more attractive product for companies and more convenient, efficient, and safer allergy immunotherapy for patients.
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Dessensibilização Imunológica/métodos , Hipersensibilidade/terapia , Pyroglyphidae/imunologia , Alérgenos/imunologia , Animais , Humanos , Hipersensibilidade/imunologia , Patentes como AssuntoRESUMO
BACKGROUND: The dawn of the "omics" technologies has changed allergy research, increasing the knowledge and identification of new allergens. However, these studies have been almost restricted to Dermatophagoides spp. Although Blomia tropicalis has long been established as a clinically important source of allergens, a thorough proteomic characterization is still lacking for this dust mite. OBJECTIVE: To increase knowledge of B. tropicalis allergens through proteomic analysis. METHODS: Eleven in-bred lineages of B. tropicalis were obtained from 11 unique different pregnant females. Their somatic extracts were analyzed and compared with a commercially available extract by liquid chromatography tandem mass spectrometry (LC-MS/MS). RESULTS: Considerable differences in the protein expression profiles were found among the breeds, and most of them displayed higher expression levels of major allergens than the commercially available extract. Blo t 2 was the most prominent allergenic protein in the analyzed extracts. Six identified allergens and 14 isoforms have not yet been recognized by IUIS. Conversely, 3 previously recognized B. tropicalis allergens were not found. CONCLUSIONS: The clear impact of inbreeding on allergen content shown by our study leads us to conclude that the quantification and/or identification of allergens from in-bred lines should be routinely considered for mite cultivation in order to select breeds with higher amounts of major allergens. In this sense, LC-MS/MS may be a useful method to achieve this quality control for research and commercial purposes.
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Alérgenos/imunologia , Extratos Celulares/imunologia , Hipersensibilidade/imunologia , Feromônios/imunologia , Sarcoptidae/imunologia , Alérgenos/isolamento & purificação , Animais , Animais Endogâmicos , Variação Biológica da População , Extratos Celulares/química , Cromatografia Líquida , Feminino , Humanos , Feromônios/isolamento & purificação , Gravidez , Especificidade da Espécie , Espectrometria de Massas em Tandem , TranscriptomaRESUMO
BACKGROUND: To diagnose and treat respiratory allergic diseases, it is important to identify the specific allergens involved. Many differences exist between common inhalant allergens depending on the residential environment and demographic factors. This study aimed to compare common inhalant allergens between Koreans and non-Koreans according to their residential region, age, and sex. METHODS: This study evaluated 15,334 individuals who underwent serum tests for multiple allergen-specific immunoglobulin E at a tertiary academic medical center between January 2010 and December 2016. The individuals included 14,786 Koreans and 548 non-Koreans. The AdvanSure™ Allostation assay (LG Life Science, Korea) was used to test for 33 inhalant allergens. RESULTS: The house dust mite (HDM) was the most common allergen in both Koreans and non-Koreans, although the proportion of individuals with HDM sensitization was greater among Koreans. High sensitization rates for various pollen types were detected among Koreans in Gangwon region, whereas Japanese cedar pollen was unique among Koreans in Jeju region. Grass pollen and animal dander were relatively common among individuals from the Americas, whereas weed and grass pollen accounted for the 10 most common allergens for individuals from Central Asia. The total sensitization rate, sensitization to HDM, and sensitization to animal dander peaked among adolescents and young adults, then subsequently decreased with age. CONCLUSIONS: This large-scale study demonstrates that various regional and age-related differences exist in the allergen sensitization rates of Koreans and non-Koreans. These data could be useful for development of avoidance measures, immunotherapy for causative allergens, and policymaking regarding allergic diseases.
Assuntos
Alérgenos/imunologia , Hipersensibilidade/diagnóstico , Hipersensibilidade/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Ásia/epidemiologia , Criança , Pré-Escolar , Alérgenos Animais/imunologia , Demografia , Europa (Continente)/epidemiologia , Feminino , Humanos , Hipersensibilidade/sangue , Imunoglobulina E/sangue , Lactente , Masculino , Pessoa de Meia-Idade , América do Norte/epidemiologia , Oceania/epidemiologia , Pólen/imunologia , Pyroglyphidae/imunologia , Grupos Raciais , América do Sul/epidemiologia , Adulto JovemRESUMO
BACKGROUND: The aim of this study was to evaluate the positivity rates of atopy patch tests for Dermatophagoides pteronyssinus, Dermatophagoides farinae and Blomia tropicalis in patients with respiratory diseases such as asthma and allergic rhinitis with or without atopic dermatitis. METHODS: The patients' clinical histories were collected, and the patients were subjected to skin prick and patch tests with the three different house dust mites on the same day. The patch tests were examined 48 hours later, and then patients were divided into two groups: I- patients with respiratory diseases, such as asthma and/or rhinitis, and atopic dermatitis and II-patients with only respiratory diseases. A total of 74 patients ranging in age from 2 to 60 years were included in this study; 16 patients were included in group I and 58 were included in group II. This study was approved by the human ethics committee of the Faculty of Medical Science and Health SUPREMA (number 2.007.135), and written informed consent was collected from each patient or their parents prior to enrollment. RESULTS: In the skin prick tests, the most prevalent mite that evoked a reaction was Dermatophagoides pteronyssinus, followed by Dermatophagoides farinae and Blomia tropicalis. Regarding the atopy patch tests, the mite that most frequently induced a positive reaction was Dermatophagoides farinae (78.4%), followed by Dermatophagoides pteronyssinus (77%) and Blomia tropicalis (52.7%). A comparison of the skin prick and atopy patch tests revealed that 53 patients (71.6%) were positive on both tests, and 30 (56.6%) patients were positivite for the same mite. We found six patients (8%) who had a positive clinical history of allergy and only exhibited positivity on the atopy patch test. DISCUSSION: Most studies have been performed with atopic dermatitis patients, but in this study, most of the patients had respiratory conditions. Blomia tropicalis is a mite that is prevalent in tropical areas, such as Brazil, and only two publications include these three mites, wich are present in Brazil. The APT may produce positive results in concordance with the SPT resuts, but may also be the only positive test ( 8%) as we observed in our study. These results suggest that the mite atopy patch test is relevant and should be considered as an additional test for patients with clinical histories of allergic respiratory disease who have negative prick test results. CONCLUSION: The APT should be considered as an additional test when the SPT and specific serum IgE tests are negative in patients with clinical histories of allergies.