RESUMO
INTRODUCTION: There has been substantial increase in food allergies in recent decades. The management of severe food allergy often includes strict avoidance and medical therapies. However, oral immunotherapy (OIT) is a promising treatment option for these patients, which is still being investigated. METHODS: The study recruited children from 2 years onward with a history of wheat anaphylaxis who had been referred to the Mofid Children Hospital. Wheat allergy was confirmed by a double-blind placebo-controlled food challenge. OIT was started to reach 5.28 g of wheat protein supplied in 60 g of bread. Besides immunologic measurements, a second and third oral food challenge (OFC) was performed after 3 months and 1 year of maintenance therapy to evaluate the long-term efficacy of wheat OIT (WOIT). RESULTS: Seventeen patients completed the 3-month maintenance phase; 8 of them demonstrated negative OFCs. All of the 9 with positive OFCs were asked to continue the daily consumption of 60 g of bread for another year. Three patients with positive OFCs were followed for 1 more year and were asked to continue eating 60 g of bread every other day. The serum level of wheat sIgE was significantly increased at the end of the buildup phase (p = 0.026) and dramatically dropped at the end of the maintenance phase (p = 0.022). CONCLUSION: To conclude, WOIT is an effective and safe modality of treatment if it is administered under strict supervision.
Assuntos
Anafilaxia , Dessensibilização Imunológica , Hipersensibilidade a Trigo , Administração Oral , Alérgenos , Anafilaxia/etiologia , Anafilaxia/terapia , Criança , Método Duplo-Cego , Seguimentos , Humanos , Fatores Imunológicos , Imunoterapia , Triticum/efeitos adversos , Hipersensibilidade a Trigo/terapiaRESUMO
BACKGROUND: Pollen is one of the most common allergens that cause respiratory allergies worldwide. Pollen grains from poplars have been reported as important sources of pollinosis in many countries. OBJECTIVE: The aim of the present study was to determine the molecular and immunochemical characterization of Pop n 2, a novel allergen of Populus nigra (P nigra) pollen extract. METHODS: In this study, the pollen extract of P nigra was analysed by SDS-PAGE, and the allergenic profile was determined by IgE immunoblotting and specific ELISA using the sera of twenty allergic patients. The coding sequence of Pop n 2 was cloned and expressed in the Escherichia coli BL21 (DE3) using plasmid the pET-21b (+). Finally, the expressed recombinant Pop n 2 was purified by affinity chromatography. RESULTS: Pop n 2 belongs to the profilin family with a molecular weight of approximately 14 kDa. Pop n 2 is the most IgE-reactive protein (about 65%) in the P nigra pollen extract. The cDNA sequencing results indicated an open reading frame 396 bp that encodes 131 amino acid residues. The results of ELISA and Immunoblotting assays showed that recombinant Pop n 2 could react with the IgE antibody in patients' sera, like its natural counterpart. CONCLUSION: Our data revealed that Pop n 2 is a significant allergen in the P nigra pollen extract. Moreover, we observed that the recombinant Pop n 2 produced by the pET-21b (+) vector in the E colisystem acts as its natural counterpart.
Assuntos
Populus , Alérgenos , Sequência de Aminoácidos , Clonagem Molecular , Reações Cruzadas , Humanos , Imunoglobulina E , Proteínas de Plantas/genética , Pólen , Populus/genética , Populus/metabolismo , Proteínas RecombinantesRESUMO
Background and aims: Allergic asthma has a considerable burden on the quality of life. A significant portion of moderate-to-severe allergic asthma patients need omalizumab, an anti-immunoglobulin-E monoclonal antibody, as an add-on therapy. In this phase III clinical trial P043 (Zerafil®, CinnaGen, Iran) efficacy, safety, and immunogenicity were compared with Xolair® (the originator omalizumab). The primary outcome was the rate of protocol-defined asthma exacerbations. Methods: Exacerbation rates, Asthma Control Test (ACT) results, spirometry measurements, immunogenicity, and safety were evaluated. Each subject received either medication with a dose ranging from 150 to 375 mg based on pre-treatment serum total IgE level (IU/mL) and body weight (kg) every two or four weeks for a duration of 28 weeks. Results: Exacerbation rates were 0.150 (CI: 0.079-0.220) in the P043 group, and 0.190 (CI: 0.110-0.270) in the omalizumab group (per-protocol). The least squares mean differences of predicted Forced Expiratory Volume in the First second (FEV1) were -2.51% (CI: -7.17-2.15, P=0.29) and -3.87% (CI: -8.79-1.04, P=0.12), pre- and post-bronchodilator use. The mean ± SD of ACT scores at the screening and the last visit were 10.62 ± 2.93 and 20.93 ± 4.26 in P043 and 11.09 ± 2.75 and 20.46 ± 5.11 in the omalizumab group. A total of 288 adverse events were reported for the 256 enrolled participants. Among all, "dyspnea" and "headache" were the most reported ones. The overall incidence of adverse events (P=0.62) and serious adverse events (P=0.07) had no significant differences between the two groups. None of the samples were positive for anti-drug antibodies. Conclusion: P043 was equivalent to omalizumab in the management of asthma in reduction of exacerbations. There was no significant difference in other efficacy and safety parameters. Clinical trial registration: www.clinicaltrials.gov (NCT05813470) and www.IRCT.ir (IRCT20150303021315N20).
Assuntos
Antiasmáticos , Asma , Medicamentos Biossimilares , Omalizumab , Humanos , Omalizumab/uso terapêutico , Omalizumab/efeitos adversos , Asma/tratamento farmacológico , Masculino , Feminino , Adulto , Método Duplo-Cego , Antiasmáticos/uso terapêutico , Antiasmáticos/efeitos adversos , Pessoa de Meia-Idade , Medicamentos Biossimilares/uso terapêutico , Medicamentos Biossimilares/efeitos adversos , Resultado do Tratamento , Equivalência Terapêutica , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Adulto Jovem , Índice de Gravidade de DoençaRESUMO
Allergic diseases are caused by the immune system's response to innocent antigens called allergens. Recent decades have seen a significant increase in the prevalence of allergic diseases worldwide, which has imposed various socio-economic effects in different countries. Various factors, including genetic factors, industrialization, improved hygiene, and climate change contribute to the development of allergic diseases in many parts of the world. Moreover, changes in lifestyle and diet habits play pivotal roles in the prevalence of allergic diseases. Dietary changes caused by decreased intake of antioxidants such as vitamin E lead to the generation of oxidative stress, which is central to the development of allergic diseases. It has been reported in many articles that oxidative stress diverts immune responses to the cells associated with the pathogenesis of allergic diseases. The aim of this short review was to summarize current knowledge about the anti-allergic properties of vitamin E.
Assuntos
Antialérgicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Hipersensibilidade/tratamento farmacológico , Sistema Imunitário/efeitos dos fármacos , Vitamina E/uso terapêutico , Animais , Humanos , Hipersensibilidade/imunologia , Hipersensibilidade/metabolismo , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Mediadores da Inflamação/metabolismo , Estresse Oxidativo/efeitos dos fármacosRESUMO
Glycyrrhizic acid (GA), the major bioactive component of glycyrrhiza, possesses anti-inflammatory, anti-allergic, and immunomodulatory activities. This study aimed to investigate the in vitro anti-allergic effect of GA through the OX40 receptor in patients with allergic rhinitis. Purified naive CD4+ T cells of patients with allergic rhinitis (n = 12) were activated with anti-CD3/anti-CD28 with and without anti-OX40 agonist mAbs and then treated with 50, 100, and 200 µM GA and 0.1 µM dexamethasone. Cells were incubated (72 h) to measure cell proliferation. Expression of OX40 in anti-OX40 mAb stimulated CD4+ T cells was evaluated by flow cytometry. mRNA expression of the OX40 receptor and T-bet, GATA-3, and forkhead box P3 (FoxP3) transcriptional factors were measured by a quantitative polymerase chain reaction. The levels of interleukin (IL)-4, IL-10, and interferon-γ (IFN-γ) were also measured. GA inhibited significantly the augmented T cell proliferation induced with anti-OX40 mAb. Protein and gene expression of OX40 was also decreased significantly. Dexamethasone and GA inhibited T-bet and GATA-3 genes expression, but this inhibition was only significant for GATA-3. In contrast, enhanced gene expression of FoxP3 was seen using 200 µM GA and dexamethasone. The levels of IL-4, IL-10, and IFN-γ decreased after treatment with both dexamethasone and GA, but the ratio of IFN-γ/IL-4 (Th1/Th2 balance) increased significantly due to 200 µM GA treatment. This study suggests that GA may have a therapeutic effect on allergic rhinitis, partly by modulation of the Th1/Th2 balance through suppression of OX40 and increasing the activity of regulatory T cells.
Assuntos
Linfócitos T CD4-Positivos/efeitos dos fármacos , Ácido Glicirrízico/farmacologia , Receptores OX40/efeitos dos fármacos , Rinite Alérgica/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Fator de Transcrição GATA3/efeitos dos fármacos , Ácido Glicirrízico/uso terapêutico , Humanos , RNA Mensageiro/análise , Receptores OX40/análise , Receptores OX40/genética , Rinite Alérgica/patologia , Linfócitos T Reguladores/efeitos dos fármacos , Células Th1/efeitos dos fármacos , Células Th2/efeitos dos fármacosRESUMO
T-cell immunoglobulin and mucin domain (TIM)-3 have been shown to negatively regulate Th1 cell-mediated immunity. Activation of TIM-3 by galectin-9 induces Th1 cell apoptosis, which may contribute to skewing of immune response towards Th2-dominant immunity. The aim of this study was to determine whether certain genetic variations of TIM-3 influence predisposition to asthma in a sample of Iranian population. This case-control study was conducted on 209 patients with asthma and 200 healthy controls. The +4259 T>G and -574 G>T polymorphisms were detected using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and amplification refractory mutation system-PCR(ARMS-PCR). Total serum IgE was further measured with ELISA. Notably, +4259T > G and-574G>T polymorphisms of TIM-3 were significantly associated with the susceptibility to asthma. In addition, the present study showed a significant difference between the distribution frequency of the GT + TT genotype and T allele on the +4259 T>G and -574 G>T locus between the groups.However, no correlation between the +4259 T > G and -574G > T polymorphisms and total serum IgE levels were observed. Together these results suggest that the TIM-3 +4259 T>G and -574 G>T polymorphisms are greatly associated with the susceptibility of Iranian population to asthma, which could open up new horizons for better understanding of the pathophysiology, diagnostic, prognostic and therapeutic approaches of asthma.
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Alelos , Asma/epidemiologia , Asma/genética , Predisposição Genética para Doença , Receptor Celular 2 do Vírus da Hepatite A/genética , Polimorfismo de Nucleotídeo Único , Adulto , Asma/imunologia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Vigilância da População , Fatores de RiscoRESUMO
The SNP (rs11209026, Arg381Gln, R381Q) in the IL-23 receptor (IL23R) confers protection against multiple inflammatory diseases, representing one of the most significant human genetic polymorphisms in inflammatory diseases. We, therefore, investigated the association between IL-23 R R381Q gene polymorphism and asthma. This case-control study was performed on 209 patients, and 200 healthy controls. Using PCR-RFLP, the R381Q variant was screened in the IL-23R gene of the patients and controls. Serum IgE levels were measured using ELISA technique. Eosinophil absolute count was done with Sesmex cell counter. Our results indicated that the genotype and allele frequencies of the IL-23R R381Q polymorphism is significantly different between asthmatic patients and control subjects (p<0.001; odd ratio= 0.266; 95%, CI=0.118-0.604. Moreover, the asthmatic patients had higher eosinophil count and total serum IgE levels than controls as expected (p<0.001). The present study suggested that R381Q polymorphism in IL-23 receptor may be a predisposing allele for asthma.
Assuntos
Asma/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Receptores de Interleucina/genética , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Asthma, affecting as many as 400 million individuals worldwide, is one of the most prevalent chronic health condition in the United States. With an increasing number of patients with asthma and the frequent inability of conventional lifestyle modification and therapy to effectively control the problem, nutritional and dietary therapies are being sought. This study was undertaken to investigate the efficacy of the purple passion fruit peel (PFP) extract, a novel mixture of bioflavonoids, on asthma symptoms. Patients with asthma were studied in a 4-week randomized, placebo-controlled, double-blind trial with oral administration of PFP extract (150 mg/d) or placebo pills. The effects of PFP extract were evaluated by assessing the clinical symptoms of asthma and spirometry tests. Most clinical symptoms of asthma of the PFP extract-treated group were moderated significantly compared to the baseline. The prevalence of wheeze, cough, as well as shortness of breath was reduced significantly in group treated with PFP extract (P < .05), whereas the placebo caused no significant improvement. Purple passion fruit peel extract supplementation resulted in a marked increase in forced vital capacity (P < .05) as placebo showed no effect. However, no significant improvement was observed in the forced expiratory volume at 1 second of those supplemented with PFP extract. No adverse effect was reported by any of study participants. The PFP extract may be safely offered to asthmatic subjects as an alternative treatment option to reduce clinical symptoms.
Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Flavonoides/uso terapêutico , Passiflora/química , Fitoterapia , Extratos Vegetais/uso terapêutico , Administração Oral , Adolescente , Adulto , Antiasmáticos/efeitos adversos , Tosse/tratamento farmacológico , Tosse/epidemiologia , Método Duplo-Cego , Dispneia/tratamento farmacológico , Dispneia/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/efeitos adversos , Prevalência , Sons Respiratórios/efeitos dos fármacos , Índice de Gravidade de Doença , Espirometria , Resultado do Tratamento , Capacidade Vital/efeitos dos fármacos , Adulto JovemRESUMO
Allergen immunotherapy involves the administration of gradually increasing quantities of specific allergens to patients with IgE-mediated conditions until a dose is reached that is effective in reducing disease severity from natural exposure. In the present study we evaluated a period of six years immunotherapy allergic rhinitis and allergic asthma patients with positive skin prick test of common aeroallergen. The immunotherapy was performed on 156 patients. One hundred twenty of the cases were allergic rhinitis (80%), 29 cases had allergic asthma and 7 cases were mixed (4.5%). 70% in allergic rhinitis group, 75% in allergic asthma group and 42.8% in mixed group completely improved. Immunotherapy, an older therapeutic method, has now been updated, and with appropriate indications, precautions and methods, has been clearly shown to be effective in the treatment of allergic rhinitis and in some cases of asthma and insect hypersensitivity.
Assuntos
Alérgenos/uso terapêutico , Asma/tratamento farmacológico , Rinite Alérgica Perene/tratamento farmacológico , Rinite Alérgica Sazonal/tratamento farmacológico , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The aim of the present study was to examine the effects of a course of aerobic exercise on pulmonary function and tolerance of activity in asthmatic patients. Among the asthmatic patients, 36 patients (M= 16, F= 20) were chosen after clinical examinations, pulmonary function test, skin prick test (SPT) for aeroallergen and a six minute walk test (6MWT) on their own free will. A patient was said to have Exercise Induced Asthma (EIA) when he/she fulfilled the following criteria; (1) FEV1 less than 80%, (2) 12% increase or more in FEV1 or PEF after short-acting ss2 agonist prescription and (3) 15% decrease in FEV1 or PEF after 6MWT with 70% or 80% of maximum heart rate. The patients were randomly put into two groups of case (M=8, F=10, Mean age=27) and control (M=8, F=10, Mean age=29). Case group participated in eight-week aerobic exercise plan, while control group had no plan of exercise. Pulmonary function tests were done before and after the course of exercise. There were significant changes in FEV1, FVC, PEF, FEF25-75%, MVV, RF and 6MWT between asthmatic patients of the two groups (P less than or equal to 0.05), but FEV1/FVC showed no significant change. Mean of changes in FEV1, FVC, PEF, FEF25-75%, MVV, RF and 6MWT were -25.56, -17.19, 32.09, -27.93, -22.18, 5.63 and -307.5 in case group respectively while they were 6.2, 4.67, 1.96, 6.65, 15.56,-2.87 and 18.78 in the control group. This study shows that aerobic exercises in asthmatic patients lead to an improvement in pulmonary functions. Aerobic exercise rehabilitation can be a complement to medical treatment of asthma.