树突状细胞与小儿变态反应性疾病的研究进展

树突状细胞是功能最强的抗原呈递细胞,也是唯一能显著刺激初始T细胞增殖的细胞。在特定条件下,它能决定机体的免疫反应向辅助性T细胞（Th）1/Th2分化。过敏性疾病是儿童时期最常见的疾病之一,最重要的免疫异常为Th2数目增多和功能亢进。作为过敏性疾病始动环节的树突状细胞,通过其表面表达的FcεRI,可促进T细胞增殖分化成Th2,并可导致一系列促炎的细胞因子/分子释放,从而引发过敏性疾病临床表现的出现。鉴于树突状细胞在过敏性疾病中的独特作用,通过各种干预措施实现对其功能的调节引起了人们越来越大的兴趣。本文就树突状细胞在小儿过敏性疾病发病机制及治疗中的作用进行综述。     

树突状细胞与小儿变态反应性疾病的研究进展

树突状细胞是功能最强的抗原呈递细胞，也是唯一能显著刺激初始T细胞增殖的细胞。在特定条件下，它能决定机体的免疫反应向辅助性T细胞（Th)1/Th2上分化。过敏性疾病是儿童时期最常见的疾病之一，最重要的免疫异常为Th2数目增多和功能亢进。作为过敏性疾病始动环节的树突状细胞，通过其表面表达的FceRI，可促进T细胞增殖分化成Th2，并可导致一系列促炎的细胞因子／分子释放，从而引发过敏性疾病临床表现的出现。鉴于树突状细胞在过敏性疾病中的独特作用，通过各种干预措施实施对其功能的调节引起了人们越来越大的兴趣。本文就树突状细胞在小儿过敏性疾病发病机制及治疗中的作用进行综述。     

维生素D与过敏性疾病相关性的研究进展

过敏性疾病的患病率在全世界呈上升趋势.流行病学调查结果显示西方发达国家维生素D制剂的使用与过敏性疾病发病率同步增加,早期补充维生素D可能增加患过敏性疾病的风险.近期研究发现维生素D缺乏的地区过敏性疾病发病率也较高,多数学者认为维生素D缺乏与过敏性疾病流行相关.研究发现维生素D参与过敏性疾病的免疫反应,如抑制Th1细胞、树突细胞发育及Th2细胞分化,参与维持肠黏膜上皮细胞屏障完整性,但无证据表明维生素D过量或缺乏可导致过敏性疾病的发生.

Abstract：

The prevalence of allergy diseases is increasing globally. Epidemiological surveies showed that the increased allergy prevalence rates followed the time trend of rickets prophylaxis in western countries. and vitamin D supplement increased the risk of allergy in early stage.Currently,most of investigators think that vltamin D deficiency may be one of the risk factors for allergy diseases.Laboratory investigations showed that vitamin D inhibited Th1、dendritic cell(DC)and Th2 cell proliferating,and keeped on epithelial suIfaces barrier tunction.However,no study has found generating of allergy disease is associated with vitamin D deftciency or excess.     

益生菌在儿童过敏性疾病的应用

过敏性疾病包括过敏性鼻炎、过敏性结膜炎、支气管哮喘、特应性皮炎、食物过敏等,已经被证实与肠道菌群的紊乱有关。过敏动物模型研究显示,益生菌能够通过诱导调节性T细胞产生,降低过敏原特异性Ig E和Th2细胞因子分泌,减轻靶器官嗜酸性粒细胞浸润和过敏性炎性反应,从而改善过敏表现。益生菌在临床上应用于婴幼儿湿疹有比较确切的治疗效果,但是用于过敏性疾病的预防证据不一致,仅在过敏性疾病高危人群中推荐使用。     

CpG基序的免疫调节作用与过敏性疾病

近来人们发现,细菌DNA和含有非甲基化胞嘧啶-鸟嘌呤(CpG)基序的某些寡核苷酸具有免疫调节作用,能够诱导辅助性T细胞(Th)1型免疫应答,并抑制Th2型免疫应答.而过敏性疾病是以Th2型免疫应答占优势为主要特征的一类疾病.动物实验及临床研究表明,CpG基序可能对预防和治疗人类过敏性疾病会有一定效果.     

Th17/Treg细胞与过敏性紫癜的免疫发病机制

过敏性紫癜是儿童时期最常见的一种自身免疫性血管炎性疾病,发病率呈逐年上升的趋势,其发病机制至今尚未完全阐明.Th17细胞是近年发现的一种新的不同于Th1、Th2的效应性CD4+T细胞亚群,近来发现,Th17/Treg失衡与过敏性紫癜的发病密切相关,本文就相关研究作一综述.     

肠道菌群与过敏

<正>过敏性疾病是儿科常见疾病,其流行病学不是很清楚,循证医学资料倾向于环境因素的重要性。"卫生假说"认为,儿童在生命早期缺乏微生物接触是导致过敏性疾病的主要因素,且儿童体内存在Th1/Th2免疫失衡,使免疫反应更倾向于Th2应答。"卫生假说"为婴儿时期应用益生菌     

CD4^＋T细胞与儿童免疫性疾病研究进展

CD4 T细胞是一群具有不同功能的异质性细胞。过去认为CD4 T细胞主要是辅助性T(Th)细胞,通常分为Th1型和Th2型。近来发现,机体存在一种新型CD4 效应T细胞Th17细胞。此细胞具有独立的分化和发育调节机制,并产生特征性的IL-17效应因子,在自身免疫性疾病和感染性疾病中发挥重要的调节作用。现就Th1/Th2细胞与Th17细胞的分化条件,及Th17细胞在自身免疫、机体防御与儿童免疫性疾病中的可能作用作一探讨。     

认识嗜酸细胞性食管炎——从基因学、免疫学到临床诊治

在欧美国家中,嗜酸细胞性食管炎已成为一种常见的以严重嗜酸性粒细胞浸润为主的消化道疾病。其发病和食物过敏、支气管哮喘、特应性皮炎及其他过敏性疾病密切相关。Th2细胞在疾病的慢性炎症中起到了至关重要的作用。文章拟综述嗜酸细胞性食管炎的基础研究进展及临床治疗。     

CpG基序的免疫调节作用与过敏性疾病

近来人们发现，细菌DNA和含有非甲基化胞嘧啶-鸟嘌呤(CpG)基序的某些寡核苷酸具有免疫调节作用，能够诱导辅助性T细胞(Th)1型免疫应答，并抑制Th2型免疫应答。而过敏性疾病是以Th2型免疫应答占优势为主要特征的一类疾病。动物实验及临床研究表明，CpG基序可能对预防和治疗人类过敏性疾病会有一定效果。     

有益菌与儿童变应性疾病

有益菌为具有活性的微生物,一定数量的有益菌可调整肠道微生物组成,刺激免疫系统成熟,诱导Th1、Treg,抑制Th2,调节Th1/Th2平衡.多个试验研究提示有益菌对儿童变应性疾病有防治作用,但具体的疗效及临床应用的安全性还需进行深入的基础和临床研究.     

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??Abstract?? Allergic disorders and rheumatic diseases are two common diseases of dysregulated immune system in children?? with the feature of long disease course and easy relapse??and the incidence of the two diseases is increasing. All these features are bad for the prognosis of children with the diseases. Prior Th1/Th2 theory deemed that Th1-mediated autoimmune diseases and Th2-mediated allergic conditions are complementary both on the mechanism and incidence?? which improve patients’ outcomes with a new balance of T cell subsets. Recent studies?? however?? have served to challenge the idea that the presence of allergy and autoimmunity are mutually exclusive states and suggest that allergic diseases and rheumatic diseases are risk factors for each other. Clear understanding of the relationship between children’s rheumatic diseases and allergic disorders will have important implications for clinical treatment and diagnosis. This article clarifies the influence of allergic diseases on children’s rheumatic disease.     

Age-related changes in intracellular cytokine profiles and Th2 dominance in allergic children

The unbalanced T helper response has been pointed out in allergic diseases. Especially in childhood, it is important to consider the development of acquired immunity. We investigated the relationship between age and Th1, Th2, Tc1 or Tc2 cells. In addition, Th1, Th2, Tc1 or Tc2 cells in allergic diseases were compared with control subjects. Thirty-four healthy controls (0-40 years old), 200 samples of cord blood, nine patients with atopic dermatitis (AD) (1-3 years old) and five patients with bronchial asthma (BA) (2-6 years old) were studied. Surface staining with CD4, CD8 and intracellular staining with anti-interferon-gamma (IFN-gamma) and anti-interleukin (IL)-4 were carried out, and analyzed by using flow cytometry. In the healthy controls, the percentages of Th1, Tc1 or Th2 showed positive correlation with age. The absolute numbers of Th1 or Tc1 also correlated with age. Cord blood with a family history of allergic disease showed no significant difference compared to that without a family history. The percentage of Th2 in AD and BA patients was significantly higher than in the age-matched healthy controls. The increase in Th1, Th2 and Tc1 with age might reflect on the development of acquired immunity. Age matching is important when evaluating the cytokine profiles of T cells. In allergic diseases, although cord blood showed a Th1-dominant pattern, it changed to Th2 dominance in childhood, and this may reflect on some genetic background.     

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??There is strong evidence implicating the intestinal flora disturbance in developing allergicdisease including allergic rhinoconjunctivitis??asthma??eczema and food allergy. Experimental studies with animal model of allergy have shown that probiotics can improve allergic manifestations by induceing immune regulation Treg cell??inhibiting the secretion of allergen-induced IgE and Th2 cytokines??attenuating eosinophils infiltration and allergic inflammation in target organs. Probiotics have been proved effective in treatment of IgE-mediated eczema;however??because of the conflicting results??probiotics are recommended for prevention of allergy only in populations at high risk of allergy.     

基于过敏性疾病和健康儿童的淋巴细胞精细分型病例对照研究

背景：过敏性疾病的诊断缺乏明确的检测标准,主要依赖于病史,在无过敏原刺激情况下则无临床症状,诊断更加困难,寻找辅助诊断过敏标志物显得非常重要。 目的：检测过敏儿童淋巴细胞精细分型特征,期望对过敏性疾病的诊断提供新的标志物。 设计：病例对照研究。 方法：选择食物和呼吸道过敏儿童作为过敏性疾病组,选择与过敏性疾病组同时期在医院健康体检正常、性别和年龄匹配的儿童为健康对照组。采用流式细胞术分析对其淋巴细胞精细分型进行检测。 主要结局指标：淋巴细胞精细分型。 结果：过敏性疾病组30例,平均年龄3.6（0.7~10.6）岁;健康对照组27名,平均年龄4.1 (0.8~11) 岁。两组年龄、性别差异无统计学意义（P分别为0.616和0.574）。T淋巴细胞精细分型：Th2细胞占效应辅助性T细胞比例和Th2/Th1比值过敏性疾病组高于健康对照组［（31.34±2.52）% vs (20.02±2.05)%,（6.86±1.51） vs (2.73±0.35)］,差异均有统计学意义。B淋巴细胞精细分型：成熟B细胞比例及绝对计数、浆母细胞绝对计数、IgE+浆母细胞比例、IgE+记忆B细胞比例,过敏性疾病组均高于健康对照组［(11.53±1.22) % vs (6.02±0.52）%,(1 068±107.3)个/μL vs (578.74±58.49）个/μL ,(40.71±6.44) 个/μL vs ( 17.08±2.93)个/μL ,(8.21±1.33) % vs (1.64±0.53）%,(4.48±0.81) % vs (0.47±0.18）%。 结论：过敏儿童Th2细胞、IgE+浆母细胞和记忆B细胞比例增高,有潜力作为辅助诊断过敏性疾病的标志物。     

Th2抑制剂在儿童过敏免疫性疾病中的应用

基于Th2细胞因子在过敏性疾病中的作用，Th2抑制剂已被认为可应用于儿童过敏性哮喘和变应性鼻炎针对靶点的药物治疗。甲磺司特是一种新型选择性Th2细胞因子抑制剂，能选择性抑制Th细胞、减少炎症介质的产生，改善过敏性疾病的症状。在日本制定的儿童支气管哮喘指南与变应性鼻炎指南中均推荐可应用甲磺司特。甲磺司特是我国首个批准上市的Th2细胞因子抑制剂，2020年成人支气管哮喘防治指南推荐可应用甲磺司特治疗支气管哮喘，但该药在我国的应用尚处于起步阶段。该文就Th2抑制剂甲磺司特在儿童过敏免疫性疾病中的应用作一综述，以促进我国儿童Th2抑制剂的规范使用。     

益生菌在儿童变态反应性疾病中的防治作用

变态反应性疾病逐年升高的发病率已引起全球的关注,严重危害儿童健康,其共同发病机制是机体对常见的吸入性或食物性过敏原产生以特异性IgE介导的或者细胞介导的免疫反应。流行病学调查、粪便菌群分析和临床研究均提示,变态反应性疾病的发生、发展与早期肠道菌群的紊乱密切相关。益生菌可调节肠道免疫反应、增加上皮细胞屏障功能和抑制病原菌的粘附定植,恢复或重建肠道正常微生物群。随着人们对变态反应性疾病认识的加深,益生菌对其防治作用将越来越受到人们的重视。     

Cord blood cytokines and chemokines and development of allergic disease

Exposure to ubiquitous allergens early in life, even before birth, may influence the incidence of allergic diseases later in life. During pregnancy, the fetomaternal interface is surrounded by high levels of T-helper (Th)2-like cytokines, possibly favouring the development of Th2-like immune responses in the offspring. The aim of this study was to evaluate the relation between cord blood (CB) IgE antibodies, Th1- and Th2-like cytokines and chemokines, maternal allergy and development of allergic disease during the first 2 yr of life in the offspring. The CB cytokine and chemokine levels from children of 20 allergic and 36 non-allergic women were determined by a multiplexed Luminex assay and ELISA. Total CB and maternal IgE antibody concentrations were quantified using ImmunoCAP technology. The maternal IgE levels during and after pregnancy correlated with CB IgE and Th2-associated macrophage-derived chemokine [MDC (CCL22)] levels. Development of allergic disease and sensitization was associated with increased CB IgE and MDC (CCL22) levels, as well as high ratios of MDC (CCL22) to Th1-associated interferon-γ inducible protein 10 [IP-10 (CXCL10)] and interferon-γ inducible T-cell α-chemoattractant [I-TAC (CXCL11) (n = 7 allergic vs. n = 25 non-allergic)]. The correlations between maternal IgE and CB IgE and MDC (CCL22) levels possibly indicate that the maternal immunity can affect the Th1/Th2 profile in the neonate. Development of allergic disease is associated with a more marked Th2-like deviation already at birth, shown as increased levels of CB IgE and MDC (CCL22) and higher ratios of MDC (CCL22) to IP-10 (CXCL10) and I-TAC (CXCL11).     

Fetal growth promotion in allergic children

Several in vitro studies have suggested the presence of Th2-skewed immunity during pregnancy in infants with atopic diseases. Our study indicated that allergic infants showed a higher birth weight and shorter gestational period at birth than those of non-allergic peers. Moreover, allergic mothers gave birth to neonates whose birth weights and gestational ages were higher and shorter than those of the non-allergic mothers, respectively. Thus, our data clearly demonstrated the promotion of intrauterine growth, either in the allergic children, or allergic mothers. Such an intrauterine environment favorable for the fetal growth may also accelerate the development of allergic diseases in their offspring that are most probably caused by the Th2-oriented immunity.     

Probiotics for allergic diseases: Realities and myths

Yao T‐C, Chang C‐J, Hsu Y‐H, Huang J‐L. Probiotics for allergic diseases: Realities and myths.
Pediatr Allergy Immunol 2010: 21: 900–919.
© 2009 John Wiley & Sons A/S The prevalence of allergic diseases such as asthma, allergic rhinitis, and atopic dermatitis has increased sharply over the past two to three decades in many countries, and allergies are now the most common chronic disease among children throughout the world. In the past few years, probiotics have been advocated for the management of allergic diseases in many parts of the world. Physicians have a responsibility to ensure the efficacy and safety of any products they prescribe or recommend. This article provides a comprehensive overview and a critical interpretation of currently available evidence regarding the role of probiotics in the prevention and treatment of allergic diseases in humans and also discusses several major myths and potential risks associated with the use of probiotics. In the current era of evidence‐based medicine, there is still insufficient evidence to recommend probiotics for the prevention of allergic diseases or as part of standard management for any allergic conditions in children.