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Identification of T- and B-Cell Subsets That Expand in the Central and Peripheral Lymphoid Organs during the Establishment of Nut Allergy in an Adjuvant-Free Mouse Model. 在无佐剂小鼠坚果过敏模型中,中央和外周淋巴器官中扩增的T细胞和b细胞亚群的鉴定
Pub Date : 2013-04-11 Print Date: 2013-01-01 DOI: 10.1155/2013/509427
Babu Gonipeta, David Duriancik, Eunjung Kim, Elizabeth Gardner, Venu Gangur

Nut allergies are potentially fatal and rarely outgrown for reasons that are not well understood. Phenotype of T- and B-cell subsets that expand during the early stages of nut allergy is largely unknown. Here we studied this problem using a novel mouse model of nut allergy. Mice were rendered hazelnut allergic by a transdermal sensitization/oral elicitation protocol. Using flow cytometry, the T- and B-cell phenotype in the bone marrow (BM), spleen, and the mesenteric lymph node (MLN) of allergic and control mice was analyzed. Nut allergic mice exhibited an expansion of CD4+ CD62L- T cells in BM and spleen; a similar trend was noted in the MLN. There was expansion of CD80+ B cells in BM and spleen and MLN and CD62L- cells in BM and spleen. Interestingly, among CD80+ B cells, significant proportion was CD73- particularly in the MLN. These data demonstrate that during the early establishment of hazelnut allergy there is (i) expansion of CD4+CD62L- T-cell subsets in both the BM and the periphery, (ii) expansion of CD80+ and CD62L- B-cell subsets in BM and the periphery, and (iii) a significant downregulation of CD73 on a subset of B cells in MLN.

坚果过敏可能是致命的,而且很少会因为不太清楚的原因而消失。在坚果过敏的早期阶段扩大的T细胞和b细胞亚群的表型在很大程度上是未知的。在这里,我们使用一种新的坚果过敏小鼠模型来研究这个问题。小鼠通过透皮致敏/口服诱导方案使榛子过敏。采用流式细胞术分析过敏小鼠和对照组骨髓(BM)、脾脏和肠系膜淋巴结(MLN)中的T细胞和b细胞表型。坚果过敏小鼠BM和脾脏中CD4+ CD62L- T细胞扩增;在多边方案中也注意到类似的趋势。BM和脾脏可见CD80+ B细胞扩增,BM和脾脏可见MLN和CD62L-细胞扩增。有趣的是,在CD80+ B细胞中,CD73占很大比例,尤其是在MLN中。这些数据表明,在榛子过敏的早期建立过程中,存在(i) BM和外周中CD4+CD62L- t细胞亚群的扩增,(ii) BM和外周中CD80+和CD62L- B细胞亚群的扩增,以及(iii) MLN中B细胞亚群上CD73的显著下调。
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引用次数: 6
Innate immune responses in house dust mite allergy. 屋尘螨过敏的先天免疫反应。
Pub Date : 2013-02-28 Print Date: 2013-01-01 DOI: 10.1155/2013/735031
Alain Jacquet

Sensitizations to house dust mites (HDM) trigger strong exacerbated allergen-induced inflammation of the skin and airways mucosa from atopic subjects resulting in atopic dermatitis as well as allergic rhinitis and asthma. Initially, the Th2-biased HDM allergic response was considered to be mediated only by allergen B- and T-cell epitopes to promote allergen-specific IgE production as well as IL-4, IL-5, and IL-13 to recruit inflammatory cells. But this general molecular model of HDM allergenicity must be revisited as a growing literature suggests that stimulations of innate immune activation pathways by HDM allergens offer new answers to the following question: what makes an HDM allergen an allergen? Indeed, HDM is a carrier not only for allergenic proteins but also microbial adjuvant compounds, both of which are able to stimulate innate signaling pathways leading to allergy. This paper will describe the multiple ways used by HDM allergens together with microbial compounds to control the initiation of the allergic response through engagement of innate immunity.

对室内尘螨(HDM)的致敏会引发过敏原诱导的皮肤和气道粘膜炎症,从而导致特应性皮炎、过敏性鼻炎和哮喘。最初,人们认为th2偏倚的HDM过敏反应仅由过敏原B和t细胞表位介导,以促进过敏原特异性IgE的产生,以及IL-4、IL-5和IL-13募集炎症细胞。但是这种HDM过敏原的一般分子模型必须重新审视,因为越来越多的文献表明HDM过敏原对先天免疫激活途径的刺激为以下问题提供了新的答案:是什么使HDM过敏原成为过敏原?事实上,HDM不仅是致敏蛋白的载体,也是微生物佐剂化合物的载体,这两种化合物都能够刺激导致过敏的先天信号通路。本文将描述HDM过敏原与微生物化合物一起通过参与先天免疫来控制过敏反应启动的多种方式。
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引用次数: 93
Thymic Stromal Lymphopoietin Enhances Th2/Th22 and Reduces IL-17A in Protease-Allergen-Induced Airways Inflammation. 胸腺基质淋巴生成素在蛋白酶过敏原诱导的气道炎症中增强Th2/Th22并降低IL-17A。
Pub Date : 2013-02-07 Print Date: 2013-01-01 DOI: 10.1155/2013/971036
Dieudonnée Togbe, Louis Fauconnier, Fahima Madouri, Tiffany Marchiol, Pauline Chenuet, Nathalie Rouxel, Aurélie Ledru, François Erard, Valerie Quesniaux, Bernhard Ryffel

Background. Thymic stromal lymphopoietin (TSLP) is induced in allergic skin and lung inflammation in man and mice. Methods. Allergic lung inflammation induced by two proteases allergens HDM and papain and a classical allergen ovalbumin was evaluated in vivo in mice deficient for TSLPR. Eosinophil recruitment, Th2 and Th17 cytokine and chemokine levels were determined in bronchoalveolar lavage fluid, lung homogenates and lung mononuclear cells ex vivo. Results. Here we report that mice challenged with house dust mite extract or papain in the absence of TSLPR have a drastic reduction of allergic inflammation with diminished eosinophil recruitment in BAL and lung and reduced mucus overproduction. TSLPR deficient DCs displayed diminished OVA antigen uptake and reduced capacity to activate antigen specific T cells. TSLPR deficient mice had diminished proinflammatory IL-1 β , IL-13, and IL-33 chemokines production, while IL-17A, IL-12p40 and IL-10 were increased. Together with impaired Th2 cytokines, IL-17A expressing TCR β (+) T cells were increased, while IL-22 expressing CD4(+) T cells were diminished in the lung. Conclusion. Therefore, TSLPR signaling is required for the development of both Th2 and Th22 responses and may restrain IL-17A. TSLP may mediate its effects in part by increasing allergen uptake and processing by DCs resulting in an exacerbated asthma.

背景。胸腺基质淋巴生成素(TSLP)在人和小鼠过敏性皮肤和肺部炎症中的诱导作用。方法。在TSLPR缺陷小鼠体内研究了两种蛋白酶过敏原HDM、木瓜蛋白酶和一种经典过敏原卵清蛋白诱导的变应性肺部炎症。体外检测支气管肺泡灌洗液、肺匀浆和肺单核细胞中嗜酸性粒细胞募集、Th2和Th17细胞因子和趋化因子水平。结果。在这里,我们报告了在没有TSLPR的情况下,用房尘螨提取物或木瓜蛋白酶刺激小鼠,变应性炎症急剧减少,BAL和肺部嗜酸性粒细胞募集减少,粘液过量产生减少。TSLPR缺陷dc表现出OVA抗原摄取减少和激活抗原特异性T细胞的能力降低。TSLPR缺陷小鼠的促炎因子IL-1 β、IL-13和IL-33的分泌减少,而IL-17A、IL-12p40和IL-10的分泌增加。在Th2细胞因子受损的情况下,肺组织中表达TCR β (+) T细胞的IL-17A增加,表达CD4(+) T细胞的IL-22减少。结论。因此,TSLPR信号是Th2和Th22反应的发展所必需的,并可能抑制IL-17A。TSLP可能在一定程度上通过增加dc对过敏原的摄取和处理而介导其作用,从而加重哮喘。
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引用次数: 18
The Relationship between Maternal Atopy and Childhood Asthma in Pretoria, South Africa. 南非比勒陀利亚母亲特应性反应与儿童哮喘的关系
Pub Date : 2013-01-27 Print Date: 2013-01-01 DOI: 10.1155/2013/164063
Salome Abbott, Piet Becker, Robin J Green

Introduction. Asthma is the commonest chronic condition of children. Diagnosis of this condition remains difficult. Many surrogate markers are used, such as documenting evidence of atopy. Method. A random sample of asthmatic children and their mothers attending the Children's Chest and Allergy Clinic at Steve Biko Academic Hospital were enrolled. Children were classified as having atopic or nonatopic asthma. Mothers completed a questionnaire to uncover atopic features. Results. Along with their mothers, 64 children with atopic asthma and 36 with nonatopic asthma were studied. The proportion of children with atopic asthma does not differ for mothers with and without a positive SPT (P = 0.836), a history of asthma (P = 0.045), symptoms suggestive of an allergic disease (P = 1.000), or who were considered to be allergic (P = 0.806). The odds ratio of a child having atopic asthma when having a mother with a doctor diagnosed history of asthma is 4.76, but the sensitivity is low (21.9%). Conclusion. The data demonstrates that all maternal allergic or asthmatic associations are poor predictors of childhood atopic asthma. Despite the increased risk of atopic asthma in a child to a mother that has a doctor diagnosis of asthma (OR 4.76 P = 0.045), this is a poor predictor of atopic asthma (sensitivity 21.9%).

介绍。哮喘是儿童最常见的慢性疾病。诊断这种疾病仍然很困难。使用了许多替代标记,例如记录特异反应的证据。方法。在史蒂夫比科学术医院的儿童胸部和过敏诊所随机抽取哮喘儿童和他们的母亲作为样本。儿童被分为特应性哮喘和非特应性哮喘。母亲们完成了一份调查问卷,以发现特应性特征。结果。研究人员对64名特应性哮喘患儿和36名非特应性哮喘患儿及其母亲进行了研究。SPT阳性和阴性母亲(P = 0.836)、哮喘史(P = 0.045)、过敏性疾病症状提示(P = 1.000)或被认为过敏的母亲(P = 0.806)患特应性哮喘的儿童比例无差异。当母亲有医生诊断的哮喘病史时,孩子患特应性哮喘的比值比为4.76,但敏感性较低(21.9%)。结论。数据表明,所有母亲过敏或哮喘关联是儿童特应性哮喘的不良预测因素。尽管医生诊断为哮喘的母亲的孩子患特应性哮喘的风险增加(OR 4.76 P = 0.045),但这并不能很好地预测特应性哮喘(敏感性21.9%)。
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引用次数: 4
Perinatal pet exposure, faecal microbiota, and wheezy bronchitis: is there a connection? 围产期宠物暴露,粪便微生物群和喘息性支气管炎:有联系吗?
Pub Date : 2013-01-09 Print Date: 2013-01-01 DOI: 10.1155/2013/827934
Merja Nermes, Katri Niinivirta, Lotta Nylund, Kirsi Laitinen, Jaakko Matomäki, Seppo Salminen, Erika Isolauri

Background. The hygiene hypothesis suggests that high hygiene standards have led to an immune dysfunction and an increase in allergic diseases. Farming-related exposures are associated with a decreased risk of asthma. Since the gut microbiota may be a pivotal component in the hygiene hypothesis, we studied whether perinatal exposure to pets, doctor's diagnosed wheezy bronchitis (WB), and compositional changes in the gut microbiota are interrelated among urban infants. Methods. Data were collected prospectively from a mother-infant nutrition study. Data on perinatal pet ownership, WB, and the microbiota composition of faecal samples of the infants assessed by quantitative PCR at 1 month were compared. Results. None of the 30 infants exposed to pets had suffered from WB by 24 months, whereas 15 of the 99 (15%) nonexposed infants had had WB (P = 0.03). The counts of Bifidobacterium longum were higher in samples (n = 17) from nonwheezing infants with pet exposure compared to those (n = 10) in wheezing infants without pet exposure (8.59/10.44 versus 5.94/9.86, resp. (median/upper limit of range, bacteria(log)/g of stool); P = 0.02). B. breve was more abundant in the wheezing infants (P = 0.02).

背景。卫生假说认为,高卫生标准导致了免疫功能障碍和过敏性疾病的增加。与农业有关的接触与哮喘风险降低有关。由于肠道微生物群可能是卫生假说的关键组成部分,我们研究了围产期接触宠物、医生诊断的喘息性支气管炎(WB)和肠道微生物群的组成变化是否与城市婴儿相关。方法。数据是从一项母婴营养研究中前瞻性收集的。比较1个月时用定量PCR评估的婴儿围产期宠物拥有量、体重和粪便样本微生物组成的数据。结果。30名接触宠物的婴儿在24个月时没有一例患有白化病,而99名未接触宠物的婴儿中有15名(15%)患有白化病(P = 0.03)。与没有接触宠物的喘息婴儿相比(n = 10),接触宠物的非喘息婴儿样本(n = 17)的长双歧杆菌计数更高(8.59/10.44 vs 5.94/9.86)。(范围中值/上限,细菌数(对数)/g);P = 0.02)。短弧菌在喘息婴儿中含量更高(P = 0.02)。
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引用次数: 38
Effect of Activated Charcoal Fibers on the Survival of the House Dust Mite, Dermatophagoides pteronyssinus: A Pilot Study. 活性炭纤维对室内尘螨生存影响的初步研究。
Pub Date : 2012-10-24 Print Date: 2012-01-01 DOI: 10.5402/2012/868170
Hae-Seon Nam, Sun-Hwa Lee, Young-Jin Choi, Joon-Soo Park, Moon-Kyun Cho, Sang-Han Lee, Julian Crane, Robert Siebers

House dust mites produce potent allergens that exacerbate asthma in sensitized patients, whom are recommended to practice allergen avoidance within their home environment. We tested the effect of activated charcoal impregnated fibers on house dust mite survival. One hundred live adult house dust mites (Dermatophagoides pteronyssinus) were added to eight culture dishes preequilibrated at room temperature (n = 4) and 70% humidity (n = 4) containing house dust mite food and active charcoal fibers. At 10 minute intervals, live and dead house dust mites were counted. All house dust mites instantly attached to the activated charcoal fibers and started to shrink almost immediately. There were no live house dust mites present as early as 40 minutes in some dishes while after 190 minutes all house dust mites were dead. In conclusion, activated charcoal fibers, if incorporated into bedding items, have the potential to control house dust mites in the indoor environment.

室内尘螨产生强效过敏原,加重致敏患者的哮喘,建议患者在家庭环境中避免过敏原。我们测试了活性炭浸渍纤维对屋尘螨存活率的影响。在室温(n = 4)和70%湿度(n = 4)条件下,将100只室内尘螨(Dermatophagoides pteronyssinus)活螨放入8个预先平衡的培养皿中,培养皿中含有室内尘螨食物和活性炭纤维。每隔10分钟,统计活尘螨和死尘螨。所有的室内尘螨都立即附着在活性炭纤维上,并几乎立即开始收缩。在一些培养皿中,早在40分钟就没有活的尘螨出现,而在190分钟后,所有的尘螨都死亡了。综上所述,活性炭纤维如果加入到床上用品中,有可能控制室内环境中的室内尘螨。
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引用次数: 1
Conditions associated with childhood asthma in north Texas. 德克萨斯州北部儿童哮喘相关疾病。
Pub Date : 2012-09-24 Print Date: 2012-01-01 DOI: 10.5402/2012/823608
Patricia Newcomb, Alaina Cyr

Introduction. The purpose of this study was to identify significant associations between asthma diagnosis, comorbid conditions, and social problems in children. Method. This study explored data collected in a unique, regional survey of children's health in north Texas originally administered in 2009 to a random sample of 21,530 households with children from 0 to 14 years of age. Descriptive statistics were compiled for the subsample of children with asthma, associations of interest were identified, and strengths of relevant associations were calculated. Results. The prevalence of asthma in school-aged children in the target area is 19-25%, which exceeds both national and state values. Statistically significant associations were found between asthma and allergies, sleep problems, and tonsillectomy. Significant associations were identified between asthma and school absences, academic problems, and behavior problems in school. There was a significantly greater prevalence of obesity/overweight among children with asthma than without asthma. Discussion. Children with asthma are at high risk for impairment in multiple dimensions. Thorough assessment, including comprehensive medical, social, and environmental histories, is critical in management of pediatric asthma.

介绍。本研究的目的是确定儿童哮喘诊断、合并症和社会问题之间的显著关联。方法。这项研究探索了在2009年对德克萨斯州北部儿童健康进行的一项独特的区域调查中收集的数据,该调查随机抽样了21,530个有0至14岁儿童的家庭。对哮喘儿童的子样本进行描述性统计,确定相关关联,并计算相关关联的强度。结果。目标地区学龄儿童哮喘患病率为19-25%,超过了国家和州的数值。统计上发现哮喘与过敏、睡眠问题和扁桃体切除术之间存在显著关联。哮喘与学校缺勤、学业问题和行为问题之间存在显著关联。哮喘儿童中肥胖/超重的患病率明显高于无哮喘儿童。讨论。患有哮喘的儿童在多个方面受到损害的风险很高。全面的评估,包括全面的医疗、社会和环境史,对儿童哮喘的管理至关重要。
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引用次数: 1
Hormonal link to autoimmune allergies. 荷尔蒙与自身免疫过敏有关
Pub Date : 2012-08-22 Print Date: 2012-01-01 DOI: 10.5402/2012/910437
Shilpa Shah

IgE recognition of autoantigens might augment allergic inflammation in the absence of exogenous allergen exposure. Among allergy and autoimmunity, there is disproportionate representation of males before puberty and females after puberty, suggesting a role for sex hormones. Hormone allergy is an allergic reaction where the offending allergens are one's own hormones. It is an immune reaction to the hormones, which can interfere with the normal function of the hormones. It can occur perimenstrually in women along with the variation in menstrual cycle. The perimenstrual allergies are about the cyclic abundance of the hormone causing a cyclic expression of allergic symptoms. The inflammatory mechanisms of allergic reactions to hormone allergens, which are intrinsic to the body, are the same as the mechanisms of allergic reactions to external allergens.

在没有外源性过敏原暴露的情况下,自身抗原的IgE识别可能会增加过敏性炎症。在过敏和自身免疫中,青春期前的男性和青春期后的女性比例不成比例,这表明性激素的作用。激素过敏是一种过敏反应,其中令人不快的过敏原是自己的激素。这是一种对激素的免疫反应,会干扰激素的正常功能。它可以发生在女性月经周期的变化。月经周围过敏是关于激素的循环丰度引起过敏症状的循环表达。激素过敏原是机体固有的,其过敏反应的炎症机制与外界过敏原的过敏反应机制相同。
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引用次数: 11
Alternative treatment for asthma: case study of success of traditional chinese medicine treatment of children from urban areas with different levels of environmental pollution. 哮喘的替代治疗:不同环境污染程度城市儿童中医治疗成功案例研究。
Pub Date : 2012-08-09 Print Date: 2012-01-01 DOI: 10.5402/2012/547534
Helen Kopnina

The present study examined efficacy of traditional Chinese medicine (TCM) treatment in Dutch children with asthma in areas with differing air pollution. The study results indicate that TCM treatment of children living in more polluted urban area is less successful then that of children living in cleaner air area.

本研究考察了荷兰不同空气污染地区儿童哮喘的中医治疗效果。研究结果表明,生活在污染较严重的城市地区的儿童的中医药治疗效果不如生活在空气较清洁地区的儿童。
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引用次数: 6
Clinical and immunological changes of immunotherapy in patients with atopic dermatitis: randomized controlled trial. 免疫治疗对特应性皮炎患者的临床和免疫学改变:随机对照试验。
Pub Date : 2012-03-07 Print Date: 2012-01-01 DOI: 10.5402/2012/183983
Jorge Mario Sánchez Caraballo, Ricardo Cardona Villa

Background. Immunotherapy has proven to be an useful tool in the management of allergic respiratory diseases; however, little has been studied in atopic dermatitis. Objective. To evaluate the clinical and immunological impact of immunotherapy with mites allergen extracts in atopic dermatitis. Methods. Patients with atopic dermatitis were assigned with computer-generated randomization to either of the following groups: (a) controls received only topical treatment with steroids and/or tacrolimus and (b) actively treated patients received topical treatment plus immunotherapy. Levels of serum total IgE, mites-specific IgE and IgG4 were assessed at study start and after one year of immunotherapy. Results. 31 patients in the active group and 29 in the control group completed the study. Symptoms and medication scores were significantly reduced in the active group after six months. Three patients in the control group showed new sensitizations to mites, while 3 patients in the active group showed neosensitization to shrimp with negative oral food challenge. We observed significant increase of mites-specific IgG4 levels in active group. Conclusion. Specific allergen immunotherapy induced a tolerogenic IgG4 response to mite allergens associated with favorable clinical effects in atopic dermatitis patients.

背景。免疫疗法已被证明是一个有用的工具,在管理过敏性呼吸道疾病;然而,对特应性皮炎的研究很少。目标。目的探讨螨类变应原提取物免疫治疗特应性皮炎的临床和免疫学效果。方法。特应性皮炎患者被计算机随机分配到以下两组:(a)对照组仅接受类固醇和/或他克莫司的局部治疗;(b)积极治疗的患者接受局部治疗加免疫治疗。在研究开始时和免疫治疗一年后评估血清总IgE、螨特异性IgE和IgG4水平。结果:治疗组31例,对照组29例完成研究。六个月后,积极组的症状和药物评分显著降低。对照组3例患者对螨出现新敏化,活性组3例患者对口服食物阴性的对虾出现新敏化。我们观察到活性组螨特异性IgG4水平显著升高。结论。特异性过敏原免疫治疗诱导对螨过敏原的耐受性IgG4反应与特应性皮炎患者良好的临床效果相关。
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引用次数: 27
期刊
ISRN allergy
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