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BACKGROUND AND OBJECTIVE: Sensitization to Blomia tropicalis is associated with asthma in various tropical and subtropical countries; however, information about the specific molecular components associated with this disease is scarce. Using molecular diagnosis, we sought to identify B tropicalis allergens associated with asthma in Colombia. METHODS: Specific IgE (sIgE) to 8 B tropicalis recombinant allergens (Blo t 2, 5, 7, 8, 10, 12, 13, and 21) was determined using an in-house ELISA system in asthma patients (n=272) and controls (n=298) recruited in a national prevalence study performed in several Colombian cities (Barranquilla, Bogotá, Medellín, Cali, and San Andrés). The study sample included children and adults (mean [SD] age, 28 [17] years). Cross-reactivity between Blo t 5 and Blo t 21 was evaluated using ELISA-inhibition. RESULTS: Specific IgE (sIgE) to 8 B tropicalis recombinant allergens (Blo t 2, 5, 7, 8, 10, 12, 13, and 21) was determined using an in-house ELISA system in asthma patients (n=272) and controls (n=298) recruited in a national prevalence study performed in several Colombian cities (Barranquilla, Bogotá, Medellín, Cali, and San Andrés). The study sample included children and adults (mean [SD] age, 28 [17] years). Cross-reactivity between Blo t 5 and Blo t 21 was evaluated using ELISA-inhibition. CONCLUSION: Although Blo t 5 and Blo t 21 are considered common sensitizers, this is the first report of their association with asthma. Both components should be included in molecular panels for diagnosis of allergy in the tropics.
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Alérgenos , Asma , Imunoglobulina E , Humanos , Asma/imunologia , Asma/diagnóstico , Asma/epidemiologia , Imunoglobulina E/imunologia , Imunoglobulina E/sangue , Adulto , Masculino , Feminino , Estudos de Casos e Controles , Criança , Adolescente , Colômbia/epidemiologia , Alérgenos/imunologia , Adulto Jovem , Pessoa de Meia-Idade , Antígenos de Plantas/imunologia , Reações Cruzadas , Clima Tropical , Prevalência , Pré-EscolarRESUMO
Background: Asthma is a multifactorial chronic disease, whose most frequent etiology is allergy, especially to Blomia tropicalis. In French Guiana, the childhood prevalence of Blomia T sensitization is unkwown. The aim of this study was to determine the proportion of sensitization to Blomia T and other mites in asthmatic children, and to describe the characteristics of childhood asthma in French Guiana. Methods: A retrospective cohort study focused on children from 0 to 18 years of age, followed for asthma at the Department of Pediatrics of the Cayenne Hospital Center in French Guiana. All asthmatic children followed by the same paediatric allergist were systematically skin-tested with Bt total extract, and Bt-specific IgE tests were additionally performed to confirm specific sensitization. All follow-up variables were collected from medical records. The outcome was sensitization to Blomia tropicalis and other allergens, and the explanatory variables were those of asthma follow-up. Patients were categorized into Blomia tropicalis sensitization yes/no. Logistic regression analysis was used to assess the relationship between follow-up variables and the outcome. Results: 302 patients were followed: 177 cases of allergic rhinitis, 135 allergic conjunctivitis, 105 atopic dermatitis, 153 food allergy, and 14 cases of drug allergy. Poly-allergy (respiratory, food, skin, and medicinal) was present in 239 children. There were 158 children followed for asthma, of whom 103 (65%) were sensitized to Blomia tropicalis. The median age of the asthmatic children sensitized to Blomia tropicalis was 7 years, and 3 years for those who were not sensitized (p < 0.001). Among the girls (n = 58), 67% were sensitized to Blomia; 97 (92%) asthmatic children co-sensitized to Blomia tropicalis, Dermatophagoides pteronyssinus, and Dermatophagoides farinae. Multivariate analysis showed that the childhood asthma in French Guiana is characterized by a median age of 7 years (p < 0.001), a high prevalence of Blomia tropicalis (p < 0.001), co-sensitization to other mites (p < 0.001), and a high prevalence of co-sensitization to cockroaches (p = 0.006). The area under the ROC curve was close to 0.9, confirming the quality of our model. Conclusion: In French Guiana, asthma is characterized by a high prevalence of Blomia tropicalis sensitization.
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Only few allergens derived from house dust mite (HDM) species have been evaluated in terms of their potential to induce allergic inflammation. In this study, we aimed to evaluate different aspects of the allergenicity and allergenic activity of Blo t 2, a Blomia tropicalis allergen. Blo t 2 was produced as a recombinant protein in Escherichia coli. Its allergenic activity was tested in humans by skin prick test and basophil activation assays, and in mice, by passive cutaneous anaphylaxis and a model of allergic airway inflammation. Sensitization rate to Blo t 2 (54.3%) was similar to that found to Blo t 21 (57.2%) and higher than to Der p 2 (37.5%). Most Blo t 2-sensitized patients showed a low intensity response (99.5%). Blo t 2 elicited CD203c upregulation and allergen induced skin inflammation. Additionally, immunized animals produced anti-Blo t 2 IgE antibodies and passive transfer of their serum to non-immunized animals induced skin inflammation after allergen exposure. Immunized animals developed bronchial hyperreactivity and a strong inflammatory lung reaction (eosinophils and neutrophils). These results confirm the allergenic activity of Blo t 2 and supports its clinical relevance.
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Alérgenos , Pyroglyphidae , Humanos , Camundongos , Animais , Dermatophagoides pteronyssinus , Imunoglobulina E , Inflamação , Antígenos de DermatophagoidesRESUMO
BACKGROUND: Allergen-specific immunotherapy (AIT) is the only disease-modifying treatment approach to change disease-causing allergens. Hypoallergenic derivatives show promise as potential therapeutics, amongst which BTH2 was designed to induce tolerance against Blomia tropicalis allergy. Our aim was to investigate the hypoallergenicity and immunoregulatory activity of BTH2 in vitro and its therapeutic potential in a mouse model of AIT. METHODS: Recombinant Blo t 5 and Blo t 21 allergens and their hybrid derivatives (BTH1 and BTH2) were expressed and purified. IgE binding capacity was tested by ELISA using sera from Brazilian, Colombian, and Ecuadorian subjects. Secretion of cytokines in supernatants from human cell cultures was measured following stimulation with the four recombinants and controls. The capacity of BTH2 to ameliorate allergic airway inflammation induced by B. tropicalis extract was evaluated in a murine model of AIT. RESULTS: rBlo t 5 and rBlo t 21 were identified as major allergens in Latin American patients, and BTH2 had the lowest IgE binding. In vitro stimulation of human cells induced greater levels of IL-10 and IFN-γ and reduced the secretion of Th2 cytokines. BTH2 ameliorated allergic airway inflammation in B. tropicalis-challenged A/J mice, as evidenced by the histopathological and humoral biomarkers: decreased Th2 cytokines and cellular infiltration (especially eosinophils), lower activity of eosinophil peroxidase, an increase in IgG blocking antibodies and strong reduction of mucus production by goblet cells. CONCLUSIONS: Our study shows that BTH2 represents a promising candidate for the treatment of B. tropicalis allergy with hypoallergenic, immune regulatory and therapeutic properties. Further pre-clinical studies are required in murine models of chronic asthma to further address the efficacy and safety of BTH2 as a vaccine against B. tropicalis-induced allergy.
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Hipersensibilidade , Humanos , Camundongos , Animais , Modelos Animais de Doenças , Hipersensibilidade/terapia , Alérgenos , Inflamação , Citocinas , Dessensibilização Imunológica , Imunoglobulina ERESUMO
BACKGROUND AND OBJECTIVES: Blomia tropicalis sensitization is associated with asthma in different tropical and sub-tropical countries; however, information about the specific molecular components associated with this disease is scarce. Using molecular diagnosis, we sought to identify B. tropicalis allergens associated with asthma in Colombia. METHODS: Specific IgE (sIgE) to eight B. tropicalis recombinant allergens (Blo t 2/5/7/8/10/12/13 and 21) was determined using an in-house developed ELISA system in asthmatic patients (n=272) and control subjects (n=298) recruited in a national prevalencestudy performed in Colombian cities (Barranquilla, Bogotá, Medellín, Cali and San Andrés). Sample study included children and adults (mean age: 28±SD 17 years old). Cross-reactivity between Blot 5 and Blo t 21 was evaluated by ELISA-inhibition. RESULTS: Sensitization to Blo t 21 (aOR: 1.9; 95% CI: 1.2 - 2.9) and Blo t 5 (aOR: 1.6; 95%CI: 1.1 - 2.5), but not Blo t 2, was associated with asthma. sIgE levels to Blo t 21 and to Blo t 5 were significantly higher in the disease group. Cross-reactivity between Blo t 21 and Blo t 5 is on average moderate; however, individual analysis indicates that may be high (>50%) in some cases. CONCLUSIONS: Although Blo t 5 and Blo t 21 has been described as common sensitizers, this is the first report of their association with asthma. Both components should be included in molecular panels for allergy diagnosis in the tropics.
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Blomia tropicalis and Dermatophagoides pteronyssinus play an important role in triggering allergy. Glycycometus malaysiensis causes IgE reaction in sensitive people, but is rarely reported in domestic dust, because it is morphologically similar to B. tropicalis making the identification of these species difficult. The identification of mites is mostly based on morphology, a time-consuming and ambiguous approach. Herein, we describe a multiplex polymerase chain reaction (mPCR) assay based on ribosomal DNA capable to identify mixed cultures of B. tropicalis, D. pteronyssinus and G. malaysiensis, and/or to identify these species from environmental dust. For this, the internal transcribed spacer 2 (ITS2) regions, flanked by partial sequences of the 5.8S and 28S genes, were PCR-amplified, cloned and sequenced. The sequences obtained were aligned with co-specific sequences available in the GenBank database for primer design and phylogenetic studies. Three pairs of primers were chosen to compose the mPCR assay, which was used to verify the frequency of different mites in house dust samples (n = 20) from homes of Salvador, Brazil. Blomia tropicalis was the most frequent, found in 95% of the samples, followed by G. malaysiensis (70%) and D. pteronyssinus (60%). Besides reporting for the first time the occurrence of G. malaysiensis in Brazil, our results confirm the good resolution of the ITS2 region for mite identification. Furthermore, the mPCR assay proved to be a fast and reliable tool for identifying these mites in mixed cultures and could be applied in future epidemiological studies, and for quality control of mite extract production for general use.
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Dermatophagoides pteronyssinus , Ácaros , Animais , Antígenos de Dermatophagoides , Brasil , Poeira , Humanos , Reação em Cadeia da Polimerase Multiplex , FilogeniaRESUMO
INTRODUCTION: Aqueous allergen injections, an effective and century-old technique, is considered a second-line approach in daily clinical practice. Inconveniences still surround conventional subcutaneous immunotherapy (SCIT) administration, such as a need for frequent injections, prolonged up-dosing schedules, elevated costs, and the unlikely possibility of a systemic reaction. The intradermal immunotherapy route (IDR) might favorably impact many of the aforementioned issues (Table 1). House dust mite (HDM) allergens are the main perennial sensitizers in the tropics, and as such, are solely employed in immunotherapy treatments. METHODS: We carried out a year-long real-life study in 25 perennial allergic rhinitis children, symptomatic on exposure to house dust, employing an intradermal low-dose allergen mix consisting of 50 ng of Dermatophagoides pteronyssinus/Dermatophagoides farinae and 120 ng of Blomia tropicalis, under a unique cost-wise protocol. Basal symptoms/signs and face Visual Analog Scale (fVAS) scores were recorded for 2 weeks and later compared with those registered throughout the 1-year treatment. Serum-specific IgG4 and IL-10 levels were employed in the assessment of the immune responses. RESULTS: Symptoms/signs and fVAS scores were significantly reduced from days 42 and 49, respectively, and remained so until treatment completion. Increases in specific IgG4's and IL-10 levels reflected significant immune responses. Injections were well tolerated and families reported improved health status (quality of life, QoL). CONCLUSIONS: A unique cost-effective immunotherapy alternative for deprived allergic communities in tropical settings is depicted; further research is needed.
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Alérgenos/administração & dosagem , Antígenos de Dermatophagoides/administração & dosagem , Dessensibilização Imunológica/economia , Rinite Alérgica Perene/terapia , Adolescente , Alérgenos/imunologia , Animais , Antígenos de Dermatophagoides/imunologia , Criança , Pré-Escolar , Análise Custo-Benefício , Dermatophagoides farinae/imunologia , Dermatophagoides pteronyssinus/imunologia , Dessensibilização Imunológica/métodos , Países em Desenvolvimento , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Injeções Intradérmicas , Interleucina-10/sangue , Interleucina-10/imunologia , Masculino , Qualidade de Vida , Rinite Alérgica Perene/sangue , Rinite Alérgica Perene/diagnóstico , Rinite Alérgica Perene/imunologia , Índice de Gravidade de Doença , Testes Cutâneos , Resultado do Tratamento , Clima TropicalRESUMO
Background: Conjunctival provocation test (CPT) is used to demonstrate clinical relevance to a specific allergen. Blomia tropicalis (Bt) is a prevalent allergen in tropical regions. Its major allergen Blo t 5 is commonly detected in house dust in Brazil. Patients with allergic rhinoconjunctivitis (ARC) have IgE antibodies to Bt although it may not indicate clinical allergy. Objective: The purpose of this study is to demonstrate the role of CPT in clinical allergy to Bt in allergic conjunctivitis (AC). Methods: CPT was performed in asymptomatic subjects with ARC (n = 26) outside the grass pollen season. They had positive skin prick tests (SPT) to Bt and other common inhalant allergens and they were off topical or systemic antihistamines. Standardized allergens were used for CPT (Blo t 5 462.5 ng/mL in 1:1 solution, Alk Abelló). CPT was conducted on a control group of subjects (n = 29) without symptoms of ARC and with negative SPT. CPT was performed with progressive doses of allergen solutions in normal saline (1:32, 1:16, 1:8, 1:4, 1:2). CPT with the same allergen dose that elicited a positive reaction was repeated one week later. The protocol was approved by the local Ethics Board and signed informed consent was obtained from all participants. Results: There were 92% (24/26) of positive CPT in subjects sensitized to Bt. Significant association was found between SPT and CPT results with Bt (p < 0.0001). CPT had 92% sensitivity and 100% specificity when compared to SPT results. Positive reactions with the same dose or one immediately higher occurred in 21 out of 22 subjects who repeated TPC 1 week later. Mild transient nasal symptoms (21/24) were the major side effects of positive CPT followed by moderate periorbital edema which occurred in 41% (10/24). One controlled asthmatic BT-sensitized subject developed wheezing and dyspnea during a positive CPT with Bt that cleared with inhaled albuterol (400 mcg). There were no reactions whatsoever of CPT in non-allergic subjects. Conclusion: This study demonstrated that Bt may cause allergic conjunctivitis in our population. In addition, CPT is a safe and reproducible test if standardized allergens are used.
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The prevalence of allergic diseases in Brazil is one of the biggest in the world. Among these pathologies, we highlight asthma as one of the most importance. Asthma is characterized as a chronic inflammatory disease of airways, associated with hyperresponsiveness. Many environmental factors can trigger asthma symptoms, among them house dust mites can stimulate hypersensitivity type I reaction. The most common in house dust mite, in tropical countries, are Dermatophagoides pteronysinus and Blomia tropicalis. Several studies have shown that helminths, especially Schistosoma mansoni, lead to reduction of symptoms of atopy and allergic diseases. Therefore, the present study aims to evaluate the ability of recombinant S. mansoni proteins Sm200, and SmKI-1 to induce immunomodulation in vitro, using peripheral blood mononuclear cells (PBMCs) from atopic and non-atopic individuals, stimulated or not with B. tropicalis extract, and in vivo, in a murine model of allergy to the mite B. tropicalis. As results, we observed that the fragment called rSm200-3 and the protein rSmKI-1 stood out for their immunomodulatory potential, stimulating IL-10 production by human PBMCs in vitro. When these proteins were associated with B. tropicalis extract, it was observed the reduction of the production of the cytokine IL-5, with a statistically significant difference in non-atopic individual's cells. In vivo, both proteins presented similar results, with a reduction of IL-5 and IL-4 levels in lung homogenates and of serum IgE. SmKI-1 was also able to decrease the levels of EPO in lung homogenates and in BAL. These results showed that both proteins were able to downmodulate Th2 cells on human PBMCs, and in a murine model of allergy. However, SmKI-1 also reduced significantly the levels of EPO in BAL and lungs showing that this protein may be a good candidate to be used as a possible replacement or in conjunction with pharmacotherapy in individuals with unregulated immune response in asthma.
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Antígenos de Helmintos/imunologia , Hipersensibilidade/imunologia , Pyroglyphidae/imunologia , Adulto , Animais , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Schistosoma mansoni/imunologia , Adulto JovemRESUMO
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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Cross-reactivity between allergens and human proteins could have a clinical impact in allergic diseases. Blo t 13 is an allergen from the mite Blomia tropicalis, which belongs to the fatty acid binding protein (FABP) family and has structural homology with human FABPs. This work aimed to map B cell epitopes on Blo t 13 and to identify epitopes involved in cross-reactivity with human heart FABP (FABP3) and adipocyte FABP (FABP4). Sera from 25 patients with house dust mite (HDM) allergy that were sensitized to Blo t 13 were used for testing the reactivity of immunoglobulin E (IgE) and IgG to FABP. The epitope mapping of Blo t 13 was performed using overlapping peptides, and cross-reactivity between Blo t 13 and human FABP was analyzed using human sera and anti-Blo t 13 monoclonal antibodies. IgE antibodies to all FABPs were detected in 14/25 serum samples, and IgG was detected in 25/25 serum samples. The cross-reactivity of Blo t 13 was 42% with FABP3 and 48% with FABP4. Two IgE-binding regions were identified in Blo t 13; one between residues 54 and 72 (the main cross-reacting region) and another between residues 111 to 129. Our results suggest that exposure to the Blo t 13 allergen could induce an auto-reactive response to endogenous FABP in allergic patients sensitized to Blo t 13.
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Alérgenos/metabolismo , Epitopos de Linfócito B/imunologia , Proteína 3 Ligante de Ácido Graxo/imunologia , Proteínas de Ligação a Ácido Graxo/imunologia , Proteínas de Ligação a Ácido Graxo/metabolismo , Adipócitos/metabolismo , Alérgenos/genética , Alérgenos/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/imunologia , Reações Cruzadas , Mapeamento de Epitopos , Proteína 3 Ligante de Ácido Graxo/química , Proteína 3 Ligante de Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/química , Proteínas de Ligação a Ácido Graxo/genética , Feminino , Humanos , Hipersensibilidade/sangue , Hipersensibilidade/patologia , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Masculino , Ácaros/metabolismo , Miocárdio/metabolismo , Estrutura Terciária de Proteína , Alinhamento de SequênciaRESUMO
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
Blomia tropicalis mite is highly prevalent in tropical and subtropical regions and it is associated with allergic diseases such as rhinitis and asthma. By using an OVA-model of allergic lung disease, we have previously shown that sensitization in the presence of toll like receptors (TLRs) agonists attenuates subsequent OVA-induced allergic responses. Here, we evaluated the effect of CpG-ODN, a specific synthetic TLR-9 agonist, on the development of experimental asthma induced by Blomia tropicalis extract, a relevant source of aeroallergens. Among different protocols of Blomia tropicalis extract sensitization, the subcutaneous sensitization in the presence of alum adjuvant induced the highest Th2 responses, including high IgE levels. Adsorption of CpG to Blomia tropicalis extract/Alum attenuated the airway hyperreactivity, the infiltration of inflammatory cells including eosinophils, and the IL-5 content in BAL. In addition, lung peribronchial inflammatory infiltrate, mucus production and IL-5-producing CD3+ CD4+ T cells were significantly reduced in the Blomia tropicalis extract/Alum+CpG group. Importantly, CpG inhibited total IgE production as well as active systemic or cutaneous anaphylaxis reactions. Inhibition of pulmonary Th2 responses was associated with increased IL-10 production but not with IFN-γ production. Notably, in IL-10-deficient mice, sensitization with OVA/Alum+CpG resulted in intense lung neutrophilia and IFN-γ production, indicating that IL-10 is necessary to inhibit subsequent Th1 immunity. Our work highlights the mechanisms of allergy attenuation by CpG and it indicates the potential use of Alum-based formulation with CpG to treat allergic processes.
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Adjuvantes Imunológicos/uso terapêutico , Compostos de Alúmen/química , Asma/prevenção & controle , Asma/parasitologia , Pyroglyphidae/fisiologia , Receptor Toll-Like 9/agonistas , Adjuvantes Imunológicos/farmacologia , Adsorção , Anafilaxia/complicações , Anafilaxia/imunologia , Anafilaxia/parasitologia , Animais , Asma/complicações , Citocinas/biossíntese , Modelos Animais de Doenças , Eosinófilos/patologia , Feminino , Hipersensibilidade/complicações , Hipersensibilidade/imunologia , Hipersensibilidade/parasitologia , Imunidade/efeitos dos fármacos , Imunização , Interleucina-10/metabolismo , Interleucina-4/biossíntese , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Linfonodos/patologia , Subpopulações de Linfócitos/efeitos dos fármacos , Subpopulações de Linfócitos/imunologia , Camundongos Endogâmicos C57BL , Neutrófilos/patologia , Oligodesoxirribonucleotídeos/farmacologia , Pyroglyphidae/efeitos dos fármacos , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Receptor Toll-Like 9/metabolismoRESUMO
INTRODUCTION: The association regarding the atopic sensitization to mite aeroallergens and the socio-environmental features is still inconsistent. OBJECTIVES: We analyzed the role played by socioeconomic and environmental factors in the prevalence of sensitization to house dust mite (HDM) allergens, and associated with the risk of developing asthma symptoms. PATIENTS AND METHODS: This is a case-control study conducted with 108 patients, aged 1-17. We inquired about family habits, socioeconomic and environmental features. We applied the International Study of Asthma and Allergies in Childhood questionnaire. RESULTS: We observed patients sensitized to all HDM tested, Derp (42%), Derf (37%) and Blot (33%). Middle family income (OR: 2.74; CI95%: 1.127-6.684), exposure to dog (OR: 3.758, CI95%: 1.127-6.684) and artificial climatization (OR: 4.319, CI95%: 1.398-13.348) were associated with sensitization to Derp. We also observed protective factors, such as sharing of dormitories, washing cycle for bedspreads and the presence of basic sanitation. An increased risk of sensitization to Derf was associated with Blot sensitization (OR: 3.172, CI95%: 1.083-9.292) and presence of mold on the walls (OR: 3.095, CI95%: 1.063-9.008). A protective factor was dormitory sharing. For sensitization to Blot, we observed an increase in the risk associated with Derp sensitization (OR: 3.462, CI95%: 1.191-10.061) and exposure to dog (OR: 3.255, CI95%: 0.987-10.736). In addition, sensitization to Blot increases the risk of developing asthma symptoms (OR: 2.732, CI95%: 0.981-7.606). CONCLUSION: Our data show distinct sociodemographic and environmental relations that lead to HDM sensitization and increased probability of development of allergic diseases.
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Asma/epidemiologia , Exposição Ambiental/efeitos adversos , Hipersensibilidade/epidemiologia , Fatores Socioeconômicos , Adolescente , Animais , Antígenos de Dermatophagoides/imunologia , Brasil/epidemiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Poeira , Feminino , Humanos , Lactente , Masculino , Prevalência , Pyroglyphidae/imunologiaRESUMO
BACKGROUND: In tropical zones, perennial exposure to house dust mite (HDM) allergens and helminth infections is present. Studying the impact of these conditions on the inception and evolution of allergic diseases is necessary to have an accurate view of their natural history. We aimed to evaluate the dynamics of genuine sensitization to Blomia tropicalis and Ascaris in children from the FRAAT birth cohort and the effects of helminth infection, environmental HDM allergen levels, and sociodemographic factors. METHODS: Children were followed up to 6 years old. Specific IgE to recombinant allergens from B. tropicalis (Blo t 5 and Blo t 12) and Ascaris spp (Asc l 3, Asc l 13 and Asc s 1) was measured by ELISA at different time points. Allergen levels were measured in dust when children were 6 months old. RESULTS: IgE sensitization increased over time up to 3 years old. Correlation among the specific IgE levels to B. tropicalis and Ascaris components is poor at year 1, but coefficients are high and significant (Spearman's rho coefficients >0.70) at year 6. Unhygienic conditions increased the odds of sensitization to B. tropicalis allergenic components. Blo t 5 levels were lower in the poorest. IgE response to Blo t 5 and Blo t 12 was less intense in children with high exposure to Blo t 5 (levels >80th percentile). CONCLUSION: In this tropical community, the pattern of childhood IgE sensitization is different from that in developing countries and is influenced by the hygienic conditions.
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Antígenos de Dermatophagoides/imunologia , Ascaris/imunologia , Exposição Ambiental/efeitos adversos , Hipersensibilidade/etiologia , Pyroglyphidae/imunologia , Alérgenos/imunologia , Animais , Criança , Pré-Escolar , Colômbia , Reações Cruzadas/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Higiene , Hipersensibilidade/epidemiologia , Imunoglobulina E/sangue , Lactente , Masculino , Fatores de Risco , Testes Cutâneos , Clima TropicalRESUMO
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.
RESUMO
BACKGROUND: High-dose aqueous subcutaneous immunotherapy is a validated and effective administration route for house dust mite and pollen allergens. OBJECTIVE: A proof-of-concept study using intradermal immunotherapy (IDIT) with low-dose house dust mite allergens (Dermatophagoides pteronyssinnus/Dermatophagoides farinae [Dp/Df] and Blomia tropicalis [Bt]) was carried out in children with allergic rhinitis symptomatic upon exposure to house dust. METHODS: Eight immunotherapy-naïve patients with positive prick skin tests and specific serum IgE to a Dp/Df mixture and to Bt were weekly administered 0.05 mL of an IDIT consisting of a phenolyzed albumin-saline preparation containing low-dose dust mites (8.3 AU [5 ng] of Dp/Df and 2.5 DBU of Bt), for 3 months. Nasal (Total Nasal Symptom Score) and facial symptoms (Visual Analog Scale) were recorded 2 weeks prior to treatment and once weekly during its course. Serial dilutions skin prick tests (1/100-1/1.000.000) and serum allergen-specific IgG4 determinations were performed at baseline and at treatment conclusion. RESULTS: Values on the scales suggested clinical improvement. There was a significant decrease in serial dilutions skin prick tests' wheal diameters, as well as an increase in serum IgG4 values at treatment completion. IDIT was well tolerated. CONCLUSION: If the present results are confirmed by further studies, allergen-specific immunotherapy wider use could be promoted.
Antecedentes: La inmunoterapia subcutánea acuosa a altas dosis es una ruta validada y efectiva de administración de alérgenos para el ácaro del polvo doméstico y alergias al polen. Objetivos: Estudio de definición conceptual empleando inmunoterapia intradérmica (ITID) con alérgenos de ácaros (Dermatophagoides pteronyssinus/Dermatophagoides farinae [Dp/Df] y Blomia tropicalis [Bt]) a bajas dosis; se llevó a cabo en niños con rinitis alérgica sintomáticos a la exposición de polvo de casa. Métodos: A ocho pacientes sin uso previo de inmunoterapia, con pruebas de punción cutánea positivas e IgE sérica específica a una mezcla de Dp/Df y Bt, se les administraron por tres meses 0.05 mL de ITID semanalmente, provenientes de una preparación fenolizada albúmino-salina y contentiva de bajas dosis de ácaros (8.3 AU= 5 ng de Dp/Df y 2.5 DBU de Bt). Los síntomas nasales (Total Nasal Symptom Score) y los faciales (Escala Análoga Visual) fueron registrados dos semanas antes del tratamiento y en el transcurso una vez a la semana. Al comienzo y al final se realizaron pruebas cutáneas diluidas y seriadas (1/100-1/1.000.000) y determinaciones de IgG4 en el suero para los alérgenos. Resultados: Los valores de las escalas sugirieron mejoría clínica. Existió disminución significativa de los diámetros de las pápulas de las pruebas diluidas y seriadas, así como aumento de los valores de la IgG4 sérica al final del tratamiento. La ITID fue bien tolerada. Conclusión: Si estudios ulteriores confirman los presentes hallazgos, se podría promover una mayor utilización de la inmunoterapia alérgeno-específica.
Assuntos
Alérgenos/administração & dosagem , Dessensibilização Imunológica/métodos , Pyroglyphidae/imunologia , Rinite Alérgica/terapia , Adolescente , Animais , Criança , Feminino , Humanos , Injeções Intradérmicas , Masculino , Projetos Piloto , Estudo de Prova de ConceitoRESUMO
Allergic diseases are considered a major problem for healthcare systems in both developed and developing countries. House dust mites are well-known triggers of allergic manifestations. While the Dermatophagoides genus is widely distributed globally, Blomia tropicalis is the most prominent mite species in the tropical and subtropical regions of the world. Over the last decades, an increase in sensitization rates to B. tropicalis has been reported, leading to increased research efforts on Blomia allergens. In fact, 8 new allergens have been identified and characterized to different degrees. Here, we provide an overview of recent developments concerning the identification and production of recombinant Blomia allergens, as well as their structural and immunological characterization. Although considerable progress has been achieved, detailed molecule-based studies are still needed to better define the clinical relevance of Blomia allergens. Thus, the establishment of a well-standardized and fully characterized panel of allergens remains a challenge for the development of better diagnosis and therapy of allergic diseases induced by B. tropicalis.
Assuntos
Alérgenos , Proteínas de Artrópodes , Ácaros/imunologia , Alérgenos/química , Alérgenos/imunologia , Alérgenos/metabolismo , Alérgenos/uso terapêutico , Animais , Proteínas de Artrópodes/química , Proteínas de Artrópodes/imunologia , Proteínas de Artrópodes/metabolismo , Proteínas de Artrópodes/uso terapêutico , Dessensibilização Imunológica , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/terapia , Processamento de Proteína Pós-Traducional , Proteínas Recombinantes/química , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/uso terapêuticoRESUMO
BACKGROUND: Asthma is a common chronic disease worldwide and Ascaris lumbricoides infection (ascariasis) is frequent in tropical regions. However, the effect of ascariasis on asthma severity has not been sufficiently explored. We sought to evaluate the influence of the IgE immune response to Ascaris extract and purified house dust mites (HDM) and Ascaris allergens on indicators of asthma severity in patients living in the tropics. METHODS: Asthmatic patients from Cartagena, Colombia were recruited. Clinical assessment included questionnaires, physical examination, allergy skin tests, spirometry, parasite stool examination and IgE antibody measurements. Asthma was diagnosed by a physician according to validated criteria. Indicators of severity were occurrence of severe dyspnea episodes, night awakenings events, > 4 emergency room (ER) visits and hospitalizations during the last year. Specific IgE to Der p 2, Ascaris spp., Blomia tropicalis and Dermatophagoides pteronyssinus extracts was determined by ImmunoCap. IgE to tropomyosins (Asc l 3, Blo t 10 and Der p 10), Blo t 5 and Asc s 1 was detected by ELISA. Logistic regression analyses were used to explore the relationships between sensitization and indicators of asthma severity. RESULTS: After adjustment for HDM sensitization, Ascaris sensitization remained associated with severe dyspnea (aOR: 1.90, 95% CI: 1.08 - 3.34, p = 0.03) and > 4 ER visits (aOR: 2.23, 95% CI: 1.15 - 4.30, p = 0.02). We also found that sensitization to the species specific markers Blo t 5 and Asc s 1, as well as the cross-reactive tropomyosins of D. pteronyssinus and Ascaris were associated with > 4 ER visits. Der p 2 sensitization was associated with bronchodilator responsiveness (aOR: 2.24: 1.25-4.02, p = 0.01). Remarkably, significantly higher IgE levels to HDM species specific allergens were found in Ascaris sensitized patients. CONCLUSIONS: In this tropical population, IgE sensitization to Ascaris and the cross-reactive tropomyosins was frequent and associated with clinical indicators of asthma severity. The significant relationship between sensitization to the nematode-specific marker Asc s 1 and ER attendance supports these findings. Moreover, ascariasis increases the human IgE responses to HDM specific allergens.