胸腺基质淋巴生成素与支气管哮喘

胸腺基质淋巴生成素(thymic stromal lymphopoietin,TSLP)是一种新近发现的、与白介素7类似的并与过敏性疾病密切相关的细胞因子,它在特应性皮炎、变应性鼻炎、变应性支气管哮喘(简称哮喘)患者明显表达,研究表明,在变应性哮喘患者中,TSLP活化树突状细胞,进而形成有利于Th2增殖极化的微环境,是导致Th1/Th2比例失衡的重要因素.TSLP可能是哮喘发病机制的免疫学机制中的一个关键因子,从而为哮喘的治疗提供一个潜在的靶点.     

TSLP基因多态性与支气管哮喘遗传易感性的关系

支气管哮喘（简称哮喘）是多基因参与的具有遗传易感性的慢性气道变应性炎症。胸腺基质淋巴细胞生成素（TSLP）是一种由上皮细胞产生的白介素7样细胞因子,与靶细胞TSLP受体相互作用,激活骨髓源性树突状细胞,并诱导一种特殊类型的炎症性Th2免疫应答,参与哮喘的发生和发展。TSLP还可通过调节核因子κB,参与哮喘的发病过程。多数家系聚集、孪生和大的遗传队列研究均证明,哮喘存在遗传易感性。靶向TSLP有望为今后哮喘免疫治疗带来新的前景。     

Epigenetic aspects of rheumatoid arthritis: contribution of non-coding RNAs

Since microRNA was discovered in the late 1990s the role of non-coding RNAs in the regulation of cellular processes has been confirmed. Intensive researches have revealed a number of subtypes of non-coding RNA. It has been proved that these molecules can influence each step of the development of cells and tissues. Moreover, researchers have found their expression change during disease development.In this article, we gathered the current results on the contribution of microRNA and long non-coding RNA in rheumatoid arthritis pathogenesis and their potential use in rheumatoid arthritis treatment. Although the present stage of studies on this matter is still very early, many studies have confirmed non-coding RNAs’ involvement in rheumatoid arthritis development. We showed ncRNAs changes in various tissues or cell lines of RA in humans or in animal models of RA. We tried to present possible mechanisms causing respective modifications of ncRNAs expression. There are some propositions to use some of them as markers of rheumatoid arthritis. Moreover, very advanced techniques of drug preparation are proposed to influence the microRNA or lncRNA pathways to inhibit inflammation in RA patients. None of them are now at the trial stage, but some are very promising.     

血清TSLP与稳定型心绞痛患者内皮功能和冠状动脉病变的关系

目的 研究血清胸腺基质淋巴细胞生成素（TSLP）水平与稳定型心绞痛（SAP）患者肱动脉内皮功能及冠状动脉病变的关系。方法 连续收集2017年5~11月在我院心血管内科经冠状动脉造影确诊的SAP患者279例和非冠心病者75例（对照组）;术前空腹留取血清待检TSLP和应用超声无创性检测肱动脉血流介导的内皮依赖性血管舒张功能（FMD）以评估血管内皮功能。应用改良Gensini积分评估冠状动脉病变的严重程度,根据结果进一步将SAP患者分为重度、中度和轻度病变亚组。结果 与对照组比较,SAP组FMD显著降低[(7.5±3.1)%比(13.2±3.8)%,P<0.01],而血清TSLP水平则显著升高[(258.2±59.2)pg/mL比(153.7±48.4)pg/mL,P<0.01]。在SAP三个亚组间比较,随冠状动脉病变由轻到重,FMD逐渐降低（P<0.01）,血清TSLP逐渐升高（P<0.05）;Logistic回归分析显示,血清TSLP是冠状动脉重度病变的独立危险因素（OR=1.707,95%CI: 1.334~2.184,P<0.01）。血清TSLP与FMD呈直线负相关（r=-0.402,P<0.01）;进一步多因素分析排除其他心血管危险因素的干扰后,前述两者之间仍存在负相关关系（β′=-0.311,P<0.01）。结论 SAP患者血清TSLP水平与肱动脉内皮功能和冠状动脉病变严重程度密切关系,提示TSLP可能参与了冠心病的病理生理过程。     

胸腺基质淋巴细胞生成素与支气管哮喘

胸腺基质淋巴细胞生成素(TSLP)是一种由上皮细胞产生的白介素7样细胞因子,与靶细胞TSLP受体相互作用,可以激活骨髓源性树突状细胞,进而诱导一种特殊类型的炎症型Th2细胞反应,而与支气管哮喘(简称哮喘)相关的致病性T细胞正是这类炎症型T细胞.TSLP还可诱导肥大细胞分泌Th2细胞因子,参与哮喘的发病过程.     

诱导支气管哮喘患者痰中IL-25、TSLP指标改变的临床价值

目的 研究诱导支气管哮喘（简称哮喘）患者痰中IL-25、胸腺基质淋巴细胞生成素（thymic stromal lymphopoietin,TSLP）指标改变的临床价值.方法 选取2012年10月至2013年12月泰山医学院附属医院就诊的哮喘患者52例作为哮喘组,另取52例健康查体者为正常对照组.按照常规方法收集诱导痰标本,应用酶联免疫吸附法（ELISA）对两组痰中IL-25以及TSLP水平进行检测,对比两组的水平差异.同时对于哮喘组患者均行抗炎药物治疗15d左右之后,检测外周血单核细胞（PBMCs）中的CD40、CD80、CD86表达水平,进行治疗前后两组表达水平.结果 哮喘组患者诱导痰中TSLP以及IL-25水平分别为（2.49±0.46） μg/L,（294.38±79.84） ng/L,均显著高于对照组的（1.45±0.36） μg/L和（181.38土56.73）ng/L,差异均有统计学意义（P＜0.05）.哮喘患者治疗后PBMCs中CD40、CD80、CD86的表达分别为（18.9±3.6）,（30.9±2.9）及（38.7±4.5）,均显著低于治疗前的（29.1±4.7）,（30.9±2.9）及（38.7±4.5）,差异均有统计学意义（P＜0.05）.结论 诱导哮喘患者痰中IL-25、TSLP指标改变的临床价值极高,为今后的哮喘治疗提供了新途径.     

Anti-TSLP antibodies: Targeting a master regulator of type 2 immune responses

TSLP is an epithelial cell-derived cytokine synthesized in response to various stimuli, including protease allergens and microorganisms like viruses and bacteria. Biological functions of TSLP require heterodimer formation between the TSLP receptor (TSLPR) and IL-7 receptor-α, which polarize dendritic cells to induce type 2 inflammation and directly expand and/or activate Th2 cells, group 2 innate lymphoid cells, basophils, and other immune cells. TSLP is thus considered a master regulator of type 2 immune responses at the barrier surfaces of skin and the respiratory/gastrointestinal tract. Indeed, genetic, experimental, and clinical evidence suggests that the TSLP-TSLPR pathway is associated with the pathogenesis of allergic diseases such as atopic dermatitis (AD) and asthma. Tezepelumab (AMG-157/MEDI9929) is a human anti-TSLP antibody that prevents TSLP-TSLPR interactions. A phase 2 trial for moderate to severe AD showed that a greater but not statistically significant percentage of tezepelumab-treated patients showed clinical improvements compared to the placebo group. A phase 2 trial for uncontrolled, severe asthma showed significant decreases in asthma exacerbation rate and improved pulmonary function and asthma control for tezepelumab-treated patients. Levels of biomarkers of type 2 inflammation, such as blood/sputum eosinophil counts and fraction of exhaled nitric oxide decreased, however, clinical efficacy was observed irrespective of the baseline levels of these biomarkers. A blockade of the TSLP-TSLPR pathway likely will exert significant clinical effects on AD, asthma, and other allergic diseases. The efficacy of anti-TSLP antibodies compared to other biologics needs to be further examined.     

Genetic analysis of H3N2 influenza A viruses isolated in 2006–2007 in Nairobi,Kenya

Background Minimal influenza surveillance has been carried out in sub‐Saharan Africa to provide information on circulating influenza subtypes for the purpose of vaccine production and monitoring trends in virus spread and mutations. Objective The aim of this study was to investigate a surveillance program in Kenya to isolate and characterize influenza viruses. Results In the 2006–2007 influenza season, nine influenza A viruses were isolated. All were of H3N2 subtype with key amino acid (aa) changes indicating that they were more closely related to recent World Health Organization recommended vaccine strains than to older vaccine strains, and mirroring the evolution of circulating influenza A globally. Hemagglutination inhibition data showed that the 2006 Kenya isolates had titers identical to the 2005–2006 H3N2 vaccine strain but two‐ to threefold lower titers to the 2006–2007 vaccine strain, suggesting that the isolates were antigenic variants of the 2006–2007 vaccine strains. Analysis of aa substitutions of hemagglutinin‐1 (HA1) protein of the 2006 Kenyan viruses revealed unique genetic variations with several aa substitutions located at immunodominant epitopes of the HA1 protein. These mutations included the V112I change at site E, the K 173 E substitution at site D and N 278 K change at site C, mutations that may result in conformational change on the HA molecule to expose novel epitopes thus abrogating binding of pre‐existing antibodies at these sites. Conclusion Characterization of these important genetic variations in influenza A viruses isolated from Kenya highlights the importance of continuing surveillance and characterization of emerging influenza drift variants in sub‐Saharan Africa.     

Treatment Trends for Eosinophilic Esophagitis and the Other Eosinophilic Gastrointestinal Diseases: Systematic Review of Clinical Trials

BackgroundEosinophilic gastrointestinal diseases (EGIDs) are chronic inflammatory disorders of the gut, including eosinophilic esophagitis (EoE), gastritis (EoG), duodenitis (EoD), gastroenteritis (EoGE), and colitis (EoC). Available treatments may be ineffective in some patients, and several clinical trials are investigating alternative treatments.AimWe performed a systematic review of clinical trials to illustrate EGIDs treatment research trends.MethodsWe searched clinicaltrials.gov to identify studies investigating EGIDs treatment. For each trial we analysed relevant data, including therapeutic intervention, method of administration, study outcomes, and temporal trends.ResultsFor EoE, 66 studies were eligible: 26 testing topical corticosteroids (39.4%), 17 (25.8%) monoclonal antibodies, eight (12.1%) dietary measures, five (7.6%) immunomodulators, one (1.5%) esophageal dilation, and nine (13.6%) other medical treatment strategies. With regard to EoG, EoD, and EoGE, 10 studies were testing monoclonal antibodies (71.5%), one immunomodulators (7.1%), one dietary measures (7.1%), and two other treatments (14.3%). There were no trials for EoC. Ongoing studies on corticosteroids are focused on novel delivery systems, including viscous suspensions, orally disintegrating tablets, or capsules. Increased research on monoclonal antibodies was seen from 2018, with interleukin (IL)-4 receptor-α, IL-5 receptor-α, IL-5, IL-13, IL-15, and Siglec-8 as the targets.ConclusionClinical trials on EGIDs are predominantly investigating corticosteroids or monoclonal antibodies. EGIDs therapeutic landscape will be trasnformed imminently.     

哮喘患者诱导痰中TSLP、IL-25水平测定及意义

目的探讨胸腺基质淋巴细胞生成素（TSLP）、IL-25在支气管哮喘（下称哮喘）发病中的作用。方法选择急性发作期及慢性期哮喘患者各15例（哮喘组）及健康查体者15例（对照组）,采用超声雾化吸入4％高渗盐水法采集诱导痰标本,以ELISA法测定诱导痰中髑LP、IL-25水平,分析两者相关性。结果哮喘组诱导痰中TSLP及IL-25水平均显著高于对照组,且急性发作期显著高于慢性期（P均〈0．05）。结论TSLP、IL-25可能在哮喘发生、发展中具有重要作用,有望作为哮喘治疗的潜在靶点。     

MicroRNA biomarkers predicting risk,initiation and progression of colorectal cancer

Colorectal cancer is a major global cause of morbidity and mortality. Current strategies employed to increase detection of early, curable stages of this disease are contributing to a reduction of the negative health impact from it. While there is a genetic component to the risk of disease, diet and environment are known to have major effects on the risk of an individual for developing the disease. However, there is the potential to reduce the impact of this disease further by preventing disease development. Biomarkers which can either predict the risk for or early stages of colorectal cancer could allow intervention at a time when prospects could be modified by environmental factors, including lifestyle and diet choices. Thus, such biomarkers could be used to identify high risk individuals who would benefit from lifestyle and dietary interventions to prevent this disease. This review will give an overview on one type of biomarker in the form of microRNAs, which have the potential to predict an individual’s risk for colorectal cancer, as well as providing a highly sensitive and non-invasive warning of disease presence and/or progression. MicroRNA biomarkers which have been studied and whose levels look promising for this purpose include MiR-18a, MiR-21, MiR-92a, MiR-135b, MiR-760, MiR-601. Not only have several individual microRNAs appeared promising as biomarkers, but panels of these may be even more useful. Furthermore, understanding dietary sources and ways of dietary modulation of these microRNAs might be fruitful in reducing the incidence and slowing the progression of colorectal cancer.     

Demographic,clinical and allergological characteristics of Eosinophilic Esophagitis in a Spanish central region

BackgroundEosinophilic esophagitis (EoE) is a chronic inflammatory emerging disease of the oesophagus with immunoallergic aetiology. The allergens involved have not been clearly defined and may depend on the exposure of the population to aeroallergens or food antigens.Materials and methodsPatients diagnosed with EoE between 2006 and 2011 were referred to our Allergy Section. Patch and skin prick tests (SPT) with aeroallergens and foods were performed, and total and specific IgE levels, eosinophil cationic protein levels and eosinophil count were determined.Results43 patients were included. 36 (83.7%) were atopic. 29 patients presented choking, 19 dysphagia, 9 food impaction with urgent endoscopy, 4 chest pain, 1 isolated vomiting and 1 epigastric pain. 22 had two or more symptoms. The mean duration of symptoms was 3.73 years. Concomitant allergic diseases included rhinoconjunctivitis and/or asthma (31 patients), IgE food allergy (21 patients) and atopic dermatitis (3 patients).32 (74%) were sensitized to aeroallergens, of which 90% were sensitized to pollens; 23 (54%) showed positive tests to foods and 12 of them (52%) to lipid transfer proteins (LTP).Of the 29 pollen-allergic patients, 15 (52%) were sensitized to plant foods and 10 (34.4%) to LTP.ConclusionsOur findings support those reported in the literature: the disease is more common in men aged 30–40 years with at least a three-year history of symptoms of esophageal dysfunction, sensitized to pollens, the predominant aeroallergen in our area, but also to plant foods or panallergens. These results increase the evidence for an immunoallergic aetiology and can help us in the early diagnosis of EoE.