RESUMEN
OBJECTIVE: Several monoclonal antibodies (MoAbs) targeting specific type 2 immune reactions have been developed as innovative therapeutic approaches for chronic inflammatory airway diseases, such as chronic sinusitis with nasal polyps (CRSwNP) and asthma. However, the clinical safety of these MoAbs and how to choose them are not clear. Therefore, we aimed to assess the systemic drug- and dose-based safety of MoAbs in chronic airway inflammation using network meta-analysis (NMA). METHODS: Electronic databases were systematically searched for relevant studies published in English between January 2009 and December 2022. Eligible studies must have clearly reported adverse events (AEs) among the MoAbs' safety data. RESULTS: 1). Regarding serious AEs, mepolizumab was significantly safer than placebo; in terms of permanent treatment discontinuation, reslizumab and dupilumab were significantly safer than benralizumab. 2). Regarding asthma worsening, dupilumab was associated with the best safety profile; was safer than dupilumab/300 mg/q2-4w. 3). In terms of injection-site reactions, dupilumab posed a higher risk than placebo; dupilumab/300 mg/qw posed a higher risk than dupilumab/300 mg/q2w and dupilumab/300 mg/q2-4w; lebrikizumab/250 mg/q4w posed a higher risk than lebrikizumab/37.5 mg/q4w; mepolizumab/100 mg/q4w posed a higher risk than mepolizumab/75 mg/q4w; benralizumab/30 mg/q4-8w posed a higher risk than benralizumab/20 mg/q4-8w. 4) In CRSwNP patients combined with asthma, the risks of experiencing AEs were not increased. CONCLUSION: Overall, biologics are safe and well tolerated in chronic inflammatory airway disease. This drug- and dose-based NMA provides further evidence on the different safety profiles of different emerging MoAbs. This information may help guide rational drug use and provide clinical recommendations for choosing MoAbs. TRIAL REGISTRATION: SYSTEMATIC REVIEW REGISTRATION (PROSPERO #CRD42023387610).
Asunto(s)
Anticuerpos Monoclonales , Asma , Pólipos Nasales , Metaanálisis en Red , Sinusitis , Humanos , Sinusitis/tratamiento farmacológico , Sinusitis/inmunología , Pólipos Nasales/tratamiento farmacológico , Pólipos Nasales/inmunología , Asma/tratamiento farmacológico , Asma/inmunología , Enfermedad Crónica , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversosRESUMEN
Background: T-helper 17 (Th17) cell response is engaged in the onset of allergic rhinitis (AR). Moreover, interleukin (IL)-38 is thought to be involved in inhibiting cytokine secretion in the Th17 pathway. Objective: To evaluate the regulatory function of IL-38 on abnormal Th17 responses in Chinese patients with AR. Methods: Forty-five participants, divided into an AR group (n=25) and a control group (n=20), were recruited for the study. In addition, the expression of IL-38 and Th17-related cytokines was measured as well as the Th17 cell count in participants. By implementing recombinant IL-38 (rIL-38), the intervention of human peripheral blood mononuclear cells (PBMCs) was performed. Then, flow cytometry, polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA) were used to detect the Th17 milieu. Results: The expression of IL-38 in the AR group notably reduced compared with that in the control, whereas Th17 cell frequency and the expression levels of its transcription factor (RORC) and cytokines (IL-17A and IL-23) increased. The differentiation and immune function of Th17 cells in PBMCs were inhibited by rIL-38. Conclusion: Th17 responses are inhibited by IL-38 in patients with AR. Therefore, the obtained findings indicate that IL-38 is a potential therapeutic target for Chinese patients with AR.
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Leucocitos Mononucleares , Rinitis Alérgica , Humanos , Leucocitos Mononucleares/metabolismo , Pueblos del Este de Asia , Citocinas/metabolismo , Antiinflamatorios , Células Th17 , Interleucinas/metabolismoRESUMEN
Allergic rhinitis (AR) is a common inflammation that affects many people globally. Quercetin has anti-allergic biological activity in AR. Here, we aimed to explore the effects of quercetin on type 1 helper T (Th1)/Th2 and regulatory T cells (Treg)/Th17 balance. We established an ovalbumin (OVA)-induced mouse model and orally administered 20, 35, and 50 mg/kg/day quercetin. The nasal symptoms of mice were observed. The immunoglobulin levels, Treg/Th17-related factors, and pro-inflammatory factors were examined by ELISA. The differentiated inflammation cells were visualized using the diff-quick staining assay. The nasal histopathology was evaluated using H&E, periodic acid Schiff (PAS), and Giemsa staining assay. The results showed that quercetin attenuated OVA-induced rubbing and sneezing. Quercetin reduced IgE, IgG1, histamine, and increased IgG2 in serum. The number of differentiated inflammation cells and goblet cells in tissues that elevated by OVA was reduced by quercetin. Moreover, OVA increased the Treg cell percentage, the levels of IL-17, TGF-ß, IL-6, TNF-α, and decreased Th17 cell percentage, IL-10 and FOXP3 levels, while quercetin abrogated their levels induced by OVA. Additionally, quercetin inactivated the NF-κB pathway. Taken together, quercetin attenuated AR symptoms by balancing the Th1/Th2, Treg/Th17 ratios, and inactivating the NF-κB pathway. The results suggested that quercetin may use for AR treatment.
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Rinitis Alérgica , Linfocitos T Reguladores , Animales , Ratones , Linfocitos T Reguladores/metabolismo , Quercetina/farmacología , Quercetina/uso terapéutico , Células Th2/metabolismo , Mucosa Nasal , FN-kappa B/metabolismo , Células Th17/metabolismo , Rinitis Alérgica/tratamiento farmacológico , Inflamación/metabolismo , Inmunoglobulina G/metabolismo , Modelos Animales de Enfermedad , Ratones Endogámicos BALB C , Citocinas/metabolismoRESUMEN
BACKGROUND: Type 2 innate lymphoid cells (ILC2) are upregulated in childhood allergic rhinitis (AR) and are associated with AR severity. This study aimed to investigate changes in the ILC2 milieu in pediatric patients with AR after sublingual immunotherapy (SLIT). METHODS: Forty- pediatric patients with AR received house dust mite (HDM) allergen extract for SLIT group and thirty pediatric patients received placebo in the study, respectively. The levels of ILC2, ILC2-related cytokines (IL-5/IL-13) and their transcription factors (GATA binding protein 3, retinoic acid-related orphan receptor α) in the circulation were assessed after 1- and 2-year SLIT. Moreover, peripheral blood mononuclear cells (PBMCs) in patients were prepared and stimulated by recombinant thymic stromal lymphopoietin, IL-25, and IL-33 after 2-year SLIT. Subsequently, the levels of ILC2, IL-5, and IL-13 were tested. RESULTS: The frequency of ILC2 and the levels of their transcription factors in the circulation were significantly decreased after SLIT in the SLIT group. The levels of ILC2-related cytokines in the SLIT group showed the same trend. The frequency of ILC2 was positively correlated with transcription factors and cytokines after SLIT. SLIT was observed to reduce the ability of HDM sensitization to generate the ILC2 milieu in PBMCs. CONCLUSIONS: Changes in the ILC2 milieu may be correlated with the curative effect and immune regulation function of SLIT. Our results suggested that the regulatory effect on ILC2 is part of the therapeutic mechanism of SLIT.
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Rinitis Alérgica , Inmunoterapia Sublingual , Niño , Humanos , Alérgenos , Citocinas , Inmunidad Innata , Factores Inmunológicos , Interleucina-13 , Interleucina-5 , Leucocitos Mononucleares , Linfocitos/metabolismo , Rinitis Alérgica/terapia , Inmunoterapia Sublingual/métodos , Factores de Transcripción , Resultado del TratamientoRESUMEN
Objective To observe the impact of leptin on the activation of group 2 innate lymphocytes (ILC2) in obese adult patients with allergic rhinitis (AR), and investigate its role and significance in the pathogenesis of AR. Methods A total of 70 patients with AR were enrolled in the study and divided into obese AR group and non-obese AR group according to body mass index (BMI), and matched with 30 cases in the healthy control group with no difference in age and gender during the same period. Flow cytometry was used to detect the ratio of ILC2 in peripheral blood mononuclear cells (PBMCs) of each group, real-time quantitative PCR to detect the expression of leptin mRNA, and ELISA to detect the serum leptin. The correlation between leptin and ILC2 was analyzed, and the changes in the ratio of ILC2 and relevant immune indexes in PBMCs of the AR group before and after the intervention of recombinant leptin were observed. Results Compared with healthy control group, the expressions of leptin and ILC2 of the AR group increased significantly, and the level of the obese AR group was significantly higher than that of the non-obese AR group. The expressions of leptin and ILC2 in the obese AR group were positively correlated in a significant manner. After the intervention of recombinant leptin, the ILC2 level of the obese AR group increased significantly. Conclusion The pathogenesis of AR in obese adults is related to its high expression of leptin, and the activation of ILC2 mediated by leptin aggravates its pathogenetic process.
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Leptina , Rinitis Alérgica , Humanos , Adulto , Leptina/metabolismo , Linfocitos , Leucocitos Mononucleares/metabolismo , Inmunidad Innata , Rinitis Alérgica/metabolismo , Obesidad/metabolismoRESUMEN
In the airway, IgE is traditionally regarded as a key mediator in allergic diseases, such as AR and allergic asthma. However, growing evidence demonstrates the importance of local IgE in airway inflammatory diseases, irrespective of the presence of allergy. In this review, we discuss the most recent evidence for IgE in chronic rhinosinusitis with nasal polyps(CRSwNP), including the local IgE's characteristics, the modulation of its synthesis, and its function. The levels of local IgE are significantly elevated in polyps independently of IgE serum levels and atopic status. Local IgE, which is correlated with type 2 inflammation, is polyclonal and functional. IgE is produced by active B cells and is dependent on the class switch recombination(CSR). In NPs, this process is triggered by not only allergens but also microbial colonization, especially the superantigen- Staphylococcus aureus. The production of local IgE is modulated by lymphocytes(such as Tfh, ILC2s, iTreg), cytokines(such as IL-4, IL-13, IFN-γ, TGF-ß, IL-2, IL-21), transcription factors, and B cell-intrinsic factor. Due to the central role of IgE in NPs, it is regarded as an ideal target for therapy and has been proved to be clinically successful. Based on this knowledge, we believe that exploring the trigger and regulatory factors for the activation of local B cells and CSR to IgE will provide more valuable information for us to recognize the pathological mechanisms of local IgE and offer the possible option for new therapeutic targets of nasal polyps.
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Pólipos Nasales , Citocinas , Humanos , Inmunidad Innata , Inmunoglobulina E , Interleucina-13 , Interleucina-2 , Interleucina-4 , Factor Intrinseco , Linfocitos/patología , Pólipos Nasales/patología , Superantígenos , Factores de Transcripción , Factor de Crecimiento Transformador betaRESUMEN
Aim: T-regulatory (Treg)/T-helper (Th) 17 imbalance contributes to the pathogenesis of allergic rhinitis (AR). Long non-coding RNAs (lncRNAs) participate in the progression of AR. Herein, the effect of lncRNA JP X on Treg/Th17 balance in AR was explored.Methods: CD4+ T cells were isolated from patients with AR and healthy control. The percentage of Treg and Th17 cells were examined by flow cytometry. The levels of JP X, miR-378g, CCL5, T GF-ß, and IL-17A were tested using qRT-P CR. The protein expression of Foxp3 and RORγt was measured by western blot.Results: The data showed that an imbalance of Treg/Th17 was associated with AR. Upregulation of JP X was found in AR, and knockdown of which improved the imbalance of Treg/Th17. Furthermore, JP X functioned as a sponge of miR-378g to upregulate CCL5. Inhibition of miR-378g reversed the effects on Treg/Th17 induced by silencing of JP X. Moreover, overexpression of CCL5 reversed miR-378g-induced effects.Conclusion: In conclusion, depletion of JP X promoted Treg/Th17 balance in AR via regulating the miR-378g/CCL5 axis. The findings provided a novel therapeutic insight for AR.
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Quimiocina CCL5 , MicroARNs , ARN Largo no Codificante , Rinitis Alérgica , Linfocitos T Reguladores , Células Th17 , Quimiocina CCL5/genética , Humanos , MicroARNs/genética , ARN Largo no Codificante/genética , Rinitis Alérgica/genética , Linfocitos T Reguladores/inmunología , Células Th17/inmunologíaRESUMEN
OBJECTIVES: Since the leptin participates in the upregulation of type 2 innate lymphoid cells (ILC2s). We investigated the role of the leptin/ILC2 axis in AR pathogenesis in Chinese paediatric patients with obesity. METHODS: Seventy AR paediatric patients with or without obesity and 30 healthy obese subjects were enrolled. The levels of leptin, its receptor and ILC2 milieu were measured, and correlations between them and clinical symptom severity and between ILC2 milieu and leptin levels were assessed. Changes of ILC2 milieu in AR patients after leptin stimulation were also detected. RESULTS: Levels of leptin, its receptor and ILC2 milieu levels were significantly higher in the disease than in the controls, and highest in the obese-AR group. The leptin/ILC2 axis and severity of clinical symptoms in obese patients with AR were significantly correlated, similarly to what was observed between leptin/leptin receptors and ILC2 milieu. Recombinant leptin could significantly increased the levels of ILC2 milieu in the obese-AR group. CONCLUSIONS: These findings suggest the unique function ofthe leptin/ILC2 axis in obese paediatric AR patients. The mechanism by which obesity promotes AR in paediatric patients may be related to the leptin/ILC2 axis.
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Obesidad Infantil , Rinitis Alérgica , Niño , Citocinas , Humanos , Inmunidad Innata , Leptina , Linfocitos , Obesidad Infantil/complicacionesRESUMEN
Patients with chronic rhinosinusitis (CRS) and allergic rhinitis (AR) (CRSwAR) have a more severe condition with a higher rate of recurrence after endoscopic sinus surgery (ESS). This study aimed to explore the effect of specific subcutaneous immunotherapy (SCIT) and nasal irrigation on CRSwAR after ESS. Sixty-four patients who were diagnosed as CRSwAR and received ESS were enrolled and divided into groups A, B, and C to receive different postoperative treatment strategies (conventional medication, medication with nasal irrigation, and medication with nasal irrigation and SCIT), and their prognosis was evaluated by scoring, electron microscopy, and inflammatory factors. One year after ESS, the recurrence rate of group C was significantly reduced; and the scoring from baseline was significantly different among the three groups, which of group C were the best. The epithelium arrangement, cilia morphology, and inflammation of nasal mucosa in each group were better than those in the preoperative state; and those in group C were the best. After one year, the expression levels of eosinophil cationic protein (ECP), interleukin (IL)-8, and IL-17 in group B were lower than those of group A; and the expression levels of ECP, IL-8, IL-25, IL-33, IL-17 in group C were lower than those in group A. SCIT combined with nasal irrigation can improve the patients' symptoms and quality of life, promote the epithelialization of the mucosa in the surgical cavity, regulate the local immune response of the nasal cavity; thus improve the prognosis of patients with ESS after 1 year.
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Inmunoterapia , Lavado Nasal (Proceso) , Cuidados Posoperatorios , Rinitis Alérgica/terapia , Rinitis/terapia , Sinusitis/terapia , Biomarcadores , Enfermedad Crónica , Toma de Decisiones Clínicas , Terapia Combinada , Citocinas , Manejo de la Enfermedad , Humanos , Inmunoterapia/métodos , Masculino , Lavado Nasal (Proceso)/métodos , Mucosa Nasal/inmunología , Mucosa Nasal/metabolismo , Cuidados Posoperatorios/métodos , Calidad de Vida , Recurrencia , Rinitis/diagnóstico , Rinitis Alérgica/diagnóstico , Sinusitis/diagnóstico , Resultado del TratamientoRESUMEN
Allergic rhinitis (AR) is a common chronic inflammatory disease of the upper respiratory tract. Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer and belongs to environmental endocrine disruptors (EDCs). It can be entered the human body which is harmful to health. The relationship between DEHP and AR is still inconclusive. This study aims to investigate the effect of environmental pollutants DEHP on AR. By examining DEHP metabolites in the urine of AR patients and building an AR model. 24 BALB/c mice were used as the study subjects, and ovalbumin (OVA) and DEHP (3 mg/kg/body) were used for intragastric administration. They were divided into control group, DEHP group, OVA group and OVA + DEHP group. Examination, behavioral scoring, inflammatory factor testing, oxidative stress testing, detection of aryl hydrocarbon receptor (AhR) and signaling pathways CYP1A1 and CYP1B1 related proteins and mRNA. The concentrations of 3 metabolites of DEHP (MEHHP, MEOHP, and MEHP) in urine of AR patients were higher. And HE-staining showed that for the control group, many chronic inflammatory cell infiltration and nasal mucosal destruction were observed in the OVA + DEHP group and were more severe than the OVA group. Allergic symptom scores were obtained from sneezing, scratching, number of scratching, and nose flow. The scores of the OVA group and the OVA + DEHP group were higher than 7 points. Serum ELISA and nasal mucosal oxidative stress tests are more serious in the OVA + DEHP group. The expression of AhR protein and its mRNA was increased in the DEHP group, OVA group and OVA + DEHP group. The OVA + DEHP group was more significant in the OVA group and DEHP group. And the mRNAs of the AhR-related signaling pathways CYP1A1 and CYP1B1 were also more prominent in the OVA + DEHP group. DEHP may aggravate its inflammatory response through the AhR pathway closely related to the environment. When combined with OVA, DEHP can further aggravate the OVA-induced nasal inflammatory response and make the nasal cavity have undergone severe changes, and many inflammatory cells have infiltrated. DEHP has shown an adjuvant effect, and the AhR-related signaling pathways CYP1A1 and CYP1B1 may be critical.
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Dietilhexil Ftalato/toxicidad , Contaminantes Ambientales/toxicidad , Rinitis Alérgica/inducido químicamente , Animales , Citocromo P-450 CYP1A1/metabolismo , Modelos Animales de Enfermedad , Exposición a Riesgos Ambientales , Inflamación/inducido químicamente , Inflamación/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/toxicidad , Estrés Oxidativo , Rinitis Alérgica/metabolismoRESUMEN
OBJECTIVES: Asthma and allergic rhinitis (AR) frequently occur as comorbid diseases of the upper airways. Single-nucleotide polymorphisms (SNPs) in the FCRL3 and FCRL5 genes have recently been shown to be associated with various immune-related disorders. This study evaluated the association of FCRL3 and FCRL5 polymorphisms with asthma and allergic rhinitis (AR) in a Han Chinese population. METHODS: Seven single nucleotide polymorphisms (SNPs) of the FCRL3 and FCRL5 were genotyped in 300 asthmatic children, and 206 healthy unrelated individuals using PCR-restriction fragment length polymorphism (PCR-RFLP) assay. Genotyping was validated by direct sequencing. RESULTS: Our results showed that the frequencies of the rs6692977 CT genotype and T allele within FCRL5 were significantly higher in asthma with comorbid AR compared to healthy controls (Bonferroni-corrected p (Pc)â¯=â¯3.75â¯×â¯10-6; Pcâ¯=â¯0.006, respectively), whereas these of the CC genotype and C allele were significantly lower (Pcâ¯=â¯4.15â¯×â¯10-5; Pcâ¯=â¯0.006, respectively). The frequencies of the rs7528684 A allele (Pcâ¯=â¯1.80â¯×â¯10-3) and the rs10489678â¯G allele (Pcâ¯=â¯0.04) within FCRL3 were higher in asthma with comorbid AR than in controls. However, no differences in the tested genetic polymorphisms were detected between asthma and healthy individuals. CONCLUSION: This study identified novel SNPs in FCRL3 and FCRL5 significantly associated with the risk for asthma with comorbid AR in the Chinese population. The genetic variants may play role in the development of the asthma phenotype in children with asthma.
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Pueblo Asiatico/genética , Asma/genética , Receptores Fc/genética , Receptores Inmunológicos/genética , Rinitis Alérgica/genética , Adolescente , Alelos , Niño , Preescolar , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Lactante , Masculino , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
BACKGROUND: Allergic rhinitis (AR) and asthma are the most common inflammatory diseases of the airways. The relationship between asthma and AR is widely and clinically recognised. The concept "one airway, one disease" has been gradually accepted. However, in China, we could not find any systematic review and meta-analysis on the prevalence of AR with asthma and asthma with AR. OBJECTIVE: The aim of this research was to carry out a meta-analysis on the results of all conducted studies to present valid information about the co-occurrence rate of AR with asthma and asthma with AR in China. METHODS: Pubmed/Medline, Science, Springer, Elsevier, Embase, Wanfang data, VIP, CBM, and CNKI were searched systemically and data were extracted from eligible studies by two independent reviewers. Meta-analysis, study quality assessment, and publication bias assessments were all done using Stata 12.1 software. RESULTS: The results of this meta-analysis showed that pooled prevalence estimates of AR with asthma ranged from 6.69% to 14.35%, asthma with AR from 26.67% to 54%. Furthermore, an overall prevalence of 10.17% (95% CI 9.08-11.27%) was ascertained for AR with asthma, and 38.97% (95% CI 34.42-43.53%) for asthma with AR. CONCLUSIONS: The present meta-analysis comprehensively provided the first quantitative summary of the prevalence of AR with asthma and asthma with AR in China. Our study demonstrated that, in China, asthma and AR are often comorbid diseases and co-exist in the same patients. There is a close correlation between AR and asthma from an epidemiological standpoint.
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Asma/epidemiología , Rinitis Alérgica/epidemiología , China/epidemiología , Comorbilidad , Humanos , PrevalenciaRESUMEN
Particulate matter (PM) is one of the most important environmental issues in China. This study aimed to explore the correlation between PM2.5 and airway inflammation in healthy rats. The PM2.5 group was given an intranasal instillation of PM2.5 suspension on 15 consecutive days, and each received oral saline from day 16 to 90. The BV intervention group was treated as the PM2.5 exposure group, except that BV instead of saline was given daily. A histopathologic examination was performed to evaluate the airway inflammation. The prevalence and function of Th1/Th2/Treg/Th17 cells were detected by flow cytometry and ELISA. The expression of AhR was detected by western blot and real-time PCR. We found that epithelial damage and increased infiltration of inflammatory cell were present in the airways after PM2.5 exposure; there was an immune imbalance of Th cells in the PM2.5 group; the expression of AhR was increased in the airways after PM2.5 exposure. In the PM2.5 + BV group, we demonstrated alleviated immune imbalance and reduced inflammatory cell infiltration in the airways. Our study showed that exposure to PM2.5 induced airway inflammation. The imbalance of Th1/Th2/Treg/Th17 in PM2.5-induced airway inflammation might be associated with activation of the AhR pathway. Oral BV reduces PM2.5-induced airway inflammation and regulates systemic immune responses in rats.
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Adyuvantes Inmunológicos/farmacología , Contaminantes Atmosféricos/efectos adversos , Hiperreactividad Bronquial/prevención & control , Extractos Celulares/farmacología , Material Particulado/efectos adversos , Neumonía/prevención & control , Células Th17/inmunología , Animales , Hiperreactividad Bronquial/etiología , Hiperreactividad Bronquial/patología , Neumonía/etiología , Neumonía/patología , RatasRESUMEN
OBJECTIVES: Allergic rhinitis (AR), a common chronic inflammatory disease in the upper airways. The prevalence of AR in children seems to be increasing recently, and the most significant causes of the increase are thought to be changes in environmental factors, especially air pollution. However, we could not find any meta-analysis on the risk of air pollution exposure on the prevalence of AR in childhood. The aim of this research was to carry out a meta-analysis on the results of recent studies (21â¯sâ¯t century) to present valid information about exposure to air pollution and risk of prevalence of childhood AR. METHODS: PubMed, Science, Google Scholar, Elsevier and MDPI web database were searched up to January 1, 2000 to February 28, 2018. Including of air pollution and AR in childhood related to the observation of literature. Meta-analysis, study quality assessment, heterogeneity analysis and publication bias test were using Stata-MP 14.1 and Review Manager version 5.3 software. RESULTS: 13 studies will be included in the meta-analysis (8 cross-sectional studies, 5 cohort studies). Exposure to NO2 (OREuropeâ¯=â¯1.031, 95%CI [1.002,1.060], Pâ¯=â¯0.033; ORAsiaâ¯=â¯1.236, 95%CI [1.099,1.390], Pâ¯=â¯0.000; ORoverallâ¯=â¯1.138, 95%CI [1.052,1.231], Pâ¯=â¯0.001); Exposure to SO2 (OREuropeâ¯=â¯1.148, 95%CI [1.030,1.279], Pâ¯=â¯0.012; ORAsiaâ¯=â¯1.044, 95%CI [0.954,1.142], Pâ¯=â¯0.352; ORoverallâ¯=â¯1.085, 95%CI [1.013,1.163], Pâ¯=â¯0.020); Exposure to PM10 (OREuropeâ¯=â¯1.190, 95%CI [1.092,1.297], Pâ¯=â¯0.000; ORAsiaâ¯=â¯1.075, 95%CI [0.995,1.161], Pâ¯=â¯0.066; ORoverallâ¯=â¯1.125, 95%CI [1.062,1.191], Pâ¯=â¯0.000); Exposure to PM2.5 (OREuropeâ¯=â¯1.195, 95%CI [1.050,1.360], Pâ¯=â¯0.007; ORAsiaâ¯=â¯1.163, 95%CI [1.074,1.260], Pâ¯=â¯0.000; ORoverallâ¯=â¯1.172, 95%CI [1.095,1.254], Pâ¯=â¯0.000). CONCLUSIONS: Exposed to air pollution probable is a risk of prevalence of childhood AR. And the prevalence of AR will be increase when exposed to NO2, SO2, PM10 and PM2.5, but maybe the relationship between SO2/PM10 and prevalence of AR are not closely in Asia.
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Contaminantes Atmosféricos , Contaminación del Aire/estadística & datos numéricos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Rinitis Alérgica/epidemiología , Asia/epidemiología , Niño , Estudios de Cohortes , Estudios Transversales , Europa (Continente)/epidemiología , Femenino , Humanos , Masculino , Dióxido de Nitrógeno , Material Particulado , Prevalencia , Factores de Riesgo , Dióxido de Azufre , Factores de TiempoRESUMEN
Allergic rhinitis (AR) is a chronic inflammatory airway disease that is caused by an abnormal T cell response. T helper (Th)-17 cells and Th2 cells are the CD4+ T cell subsets implicated in the pathogenesis of AR. The suppression of excessive responses of these Th17 and Th2 cells has been reported to be an effective therapeutic approach to treat AR patients, and continuous efforts are being undertaken to find new methods to modulate the function of these cells. Recent studies have shown that IL-1R8 and its ligand IL-37 negatively regulate the immune response. In this study, we investigated the immunomodulatory the roles of IL-37/IL-1R8 axis in AR patients. We found that IL-1R8 expression was very low on dendritic cells (DCs) and resting CD4+ T cells but increased strongly on CD4+ T cells following T cell activation. Furthermore, IL-1R8 expression on CD4+ T cells was markedly higher in AR patients than in healthy controls. The IL-1R8 ligand IL-37 could act on CD4+ T cells to inhibit IL-17 and IL-4 production but could not influence DC-induced IL-17- and IL-4-producing CD4+ T cell responses. Meanwhile, recombinant IL-37 (rIL-37) did not influence IL-6, IL-1ß, and IL-10 production by DCs and expression of co-stimulatory molecules (including CD80, CD40, CD86 and HLA-DR) in DCs. Thus, IL-37 may regulate aberrant T cell immune response of allergic rhinitis mainly through CD4+ T cells, not DCs. The immunomodulatory roles of the IL-37/IL-1R8 axis indicate the therapeutic potential of this axis in AR.
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Citocinas/inmunología , Receptores de Interleucina-1/inmunología , Rinitis Alérgica/inmunología , Linfocitos T CD4-Positivos/inmunología , Células Dendríticas/inmunología , Femenino , Humanos , Ligandos , Masculino , Receptores de Interleucina-1/genéticaRESUMEN
Interleukin37 (IL37), a novel member of the IL1 cytokine family has been identified as a natural suppressor of innate immunity and inflammatory responses. The present study aimed to determine the expression of IL37 in peripheral blood mononuclear cells (PBMCs) from patients with allergic rhinitis (AR), and examine the possible immunosuppressive effect of IL37 on inflammatory mediators and CD4+ T cells in the pathogenesis of AR. The expression levels of IL37 were determined in PBMCs from 39 patients with AR and 43 controls using reverse transcriptionquantitative polymerase chain reaction (RTqPCR) analysis and flow cytometry. Cytokines in the supernatants of the PBMCs and CD4+ T cells, which were stimulated with lipopolysaccharide in the presence or absence of IL37, were assayed using enzymelinked immunosorbent assays and RTqPCR analysis. The results showed that the patients with AR exhibited significantly decreased expression of IL37, and increased expression levels of interleukin (IL)1ß and IL6 in PBMCs. Recombinant IL37 (rIL37) inhibited the production of IL1p and IL6, and enhanced the production of IL27 in PBMCs from the patients with AR and the control individuals. rIL37 also markedly decreased the expression of IL17 by CD4+ T cells in the patients with AR and controls. These results suggested that IL37 may be an important cytokine in the pathogenesis of AR. It may have a protective role in AR by inhibiting the production of proinflammatory cytokines and through suppressive regulation of the Th17 response.
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Interleucina-1/metabolismo , Rinitis Alérgica/metabolismo , Adolescente , Adulto , Células Cultivadas , Niño , Femenino , Expresión Génica , Humanos , Interleucina-1/genética , Masculino , Persona de Mediana Edad , Rinitis Alérgica/inmunología , Adulto JovenRESUMEN
The present document is based on a consensus reached by a panel of experts from Chinese Society of Allergy (CSA) and Chinese Allergic Rhinitis Collaborative Research Group (C2AR2G). Allergen immunotherapy (AIT), has increasingly been used as a treatment for allergic rhinitis (AR) globally, as it has been shown to provide a long-term effect in improving nasal and ocular symptoms, reducing medication need, and improving quality of life. AIT is currently the only curative intervention that can potentially modify the immune system in individuals suffering from AR and prevent the development of new sensitization and the progression of disease from AR to asthma. Although the use of AIT is becoming more acceptable in China, to date no AR immunotherapy guideline from China is available for use by the international community. This document has thus been produced and covers the main aspects of AIT undertaken in China; including selection of patients for AIT, the allergen extracts available on the Chinese market, schedules and doses of allergen employed in different routes of AIT, assessment of effect and safety, patients' administration and follow-up, and management of adverse reactions. The Chinese guideline for AR immunotherapy will thus serve as a reference point by doctors, healthcare professionals and organizations involved in the AIT of AR in China. Moreover, this guideline will serve as a source of information for the international community on AIT treatment strategies employed in China.
RESUMEN
Allergic rhinitis (AR) is a common inflammatory disease of the upper airway. Recent evidence suggests that genegene interactions between tumor necrosis factor receptor superfamily 4 (TNFSF4) and B cell lymphocyte kinase (BLK) may have a synergistic effect on T and B cells in determining immunologic aberration, via the nuclear factorκB pathway. The present study was performed to evaluate the potential association between specific single nucleotide polymorphisms (SNPs) in the TNFSF4 and BKL genes with susceptibility to AR in Chinese subjects. A populationbased casecontrol study was performed in 600 Chinese AR patients and 700 controls. Blood was drawn for DNA extraction, and 9 SNPs (6 in TNFSF4 and 3 in BKL genes) were selected and genotyped. The TNFSF4 SNPs rs1234314 and rs1234315, and the BLK SNPs rs13277113 and rs1600249 were observed to occur in different frequencies between the AR patients and the controls. The CC (rs1234314, rs1234315) and AA (rs1600249, rs13277113) genotypes provided protective effects against AR, whereas the AG (rs13277113) genotype presented a risk factor for AR. The haplotypes ACC in the rs1234313rs1234314rs1234315 block and GA in the rs2254546rs13277113 block significantly decreased the risk of AR, whereas the GGT and AG haplotypes served protective roles. SNP interaction analysis further indicated that there may be synergistic effects among the selected sets of polymorphisms. The present study suggests a novel association between specific TNFSF4 and BLK gene polymorphisms and AR risk, highlighting their potential utility as genetic biomarkers for AR susceptibility in a Chinese Han population.
Asunto(s)
Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Ligando OX40/genética , Polimorfismo de Nucleótido Simple/genética , Rinitis Alérgica/genética , Familia-src Quinasas/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Niño , Demografía , Epistasis Genética , Femenino , Frecuencia de los Genes/genética , Sitios Genéticos , Haplotipos/genética , Humanos , Masculino , Persona de Mediana Edad , Reducción de Dimensionalidad Multifactorial , Adulto JovenRESUMEN
NFBD1, a signal amplifier of the p53 pathway, is vital for protecting cells from p53-mediated apoptosis and the early phase of DNA damage response under normal culture conditions. Here we investigated its expression in patients with nasopharyngeal carcinoma (NPC), and we describe the biological functions of the NFBD1 gene. We found that NFBD1 mRNA and protein were more highly expressed in NPC tissues than in nontumorous tissues. To investigate the function of NFBD1, we created NFBD1-depleted NPC cell lines that exhibited decreased cellular proliferation and colony formation, an increase in their rate of apoptosis, and an enhanced sensitivity to chemotherapeutic agents compared with in vitro controls. However, N-acetyl cysteine (NAC) and downregulation of p53 expression could partially reverse the apoptosis caused by the loss of NFBD1. Further analysis showed that loss of NFBD1 resulted in increased production of intracellular reactive oxygen species (ROS) depending on p53, which subsequently triggered the mitochondrial apoptotic pathway. Using a xenograft model in nude mice, we showed that silencing NFBD1 also significantly inhibited tumor growth and led to apoptosis. Taken together, our data suggest that inhibition of NFBD1 in NPC could be therapeutically useful.