Pimecrolius on T cell Responses in Atopic March

皮美克留斯 (Pimecrolius) 论特应性三月中的 T 细胞反应

• 批准号: 7347525
• 负责人: JONATHAN Micheal SPERGEL
• 金额: $ 37.05万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-15 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7347525
• 关键词: Agonist; Albuterol; Allergens; Asthma; Atopic Dermatitis; Betula Genus; Biological Assay; Breathing; Cells; Child; Clinical Trials; Controlled Study; Cream; Cutaneous; Development; Diagnosis; Disease; Double-Blind Method; Early treatment; Exhalation; Felis catus; Flow Cytometry; Frequencies; Goals; HLA Antigens; Homing; IgE; Infant; Measures; Nitric Oxide; Novartis brand of pimecrolimus; Patients; Peripheral Blood Mononuclear Cell; Pharmacologic Substance; Phenotype; Pimecrolimus; Pollen; Prevalence; Prevention; Process; Production; Pyroglyphidae; Randomized; Role; Safety; Serum; Skin; Spirometry; Staphylococcus aureus; Superantigens; T-Cell Activation; T-Lymphocyte; absorption; airborne allergen; atopy; cytokine; improved; lymphocyte proliferation; prophylactic; respiratory; response

DESCRIPTION (provided by applicant): The overall goal of this project is to understand the atopic march and the role of the skin in this process of systemic allergen sensitization in children with atopic dermatitis (AD). Our overall hypothesis is that AD results in increased skin allergen absorption and systemic allergen sensitization reflected in high IgE levels. This makes patients with AD prone to the development of respiratory allergy (Atopic March). Improving skin barrier function with prophylactic topical pimecrolimus would reduce allergen absorption, allergen sensitization and reduce the prevalence of asthma. This would be evidenced by a decreased expression of cutaneous leukocyte antigen (CLA)+ TH2 cells in the pimecrolimus treated group. The clinical trial of pimecrolimus "A 3-year, randomized, double-blind vehicle controlled study to evaluate the safety and efficacy of Elidel 1% cream in modifying the course of AD in infants" is being supported by Novartis Pharmaceutical Co. provides an unique opportunity to study the mechanism of atopic dermatitis and the atopic march. Our proposed study has three aims in examining the atopic march and possible prevention. The first aim will examine specific and total allergen sensitization by allergen-specific and total IgE. The second aim will be examining mechanistic parts of this study. We will explore the frequency of skin homing T cells, their cytokine expression and the effect of staphylococcal superantigen on their expression. In third aim of the trial, we explore the effects of pimecrolimus as a disease-modifying agent in the prevention of asthma. Asthma phenotype will be examined by spirometry per and post-beta-2-agonist and exhaled nitric oxide.

描述(申请人提供)：这个项目的总体目标是了解特应性进行期和皮肤在特应性皮炎(AD)儿童全身过敏原敏化过程中的作用。我们的总体假设是，AD导致皮肤变应原吸收增加和全身变应原敏化，反映为高IgE水平。这使得阿尔茨海默病患者更容易发展为呼吸系统过敏(Atopal March)。预防性外用吡美莫司可改善皮肤屏障功能，减少变应原吸收、变应原敏化，降低哮喘发病率。在吡美莫司治疗组中，皮肤白细胞抗原(CLA)+TH2细胞的表达减少就是证据。诺华制药公司正在支持吡美莫司的临床试验，这是一项为期3年的随机双盲载体对照研究，旨在评估1%Elidel乳膏改变婴儿AD病程的安全性和有效性。这为研究特应性皮炎的机制和特应性进行曲提供了一个独特的机会。我们建议的研究有三个目的，以检查特应性进行症和可能的预防。第一个目标是通过过敏原特异性和总IgE检测特异性和总过敏原致敏性。第二个目标将是检查这项研究的机械部分。我们将探讨皮肤归巢T细胞的频率、其细胞因子的表达以及葡萄球菌超抗原对其表达的影响。在试验的第三个目的中，我们探索了吡美莫司作为疾病改良剂在预防哮喘中的作用。哮喘的表型将通过吸入β-2激动剂和呼出的一氧化氮后的肺活量测定法进行检查。

项目成果

Study of the Atopic March: Development of Atopic Comorbidities.

特应性游行的研究：特应性合并症的发展。

• DOI: 10.1111/pde.12867
• 发表时间: 2016
• 期刊: Pediatric dermatology
• 影响因子: 1.5
• 作者: Schneider,Lynda;Hanifin,Jon;Boguniewicz,Mark;Eichenfield,LawrenceF;Spergel,JonathanM;Dakovic,Rada;Paller,AmyS
• 通讯作者: Paller,AmyS

The link between allergies and eosinophilic esophagitis: implications for management strategies.

• DOI: 10.1586/eci.09.74
• 发表时间: 2010-01
• 期刊: Expert review of clinical immunology
• 影响因子: 4.4
• 作者: Brown-Whitehorn TF;Spergel JM
• 通讯作者: Spergel JM