Immune progression and plasticity in relation to child age

与儿童年龄相关的免疫进展和可塑性

• 批准号: 9308334
• 负责人: WAYNE G SHREFFLER
• 金额: $ 23.5万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-01 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9308334
• 关键词: 5 year old; Adult; Age; Allergens; Allergic; Allergic Disease; Allergy to peanuts; Biological; Child; Childhood; Chronic; Clinical; Clinical Data; Clinical Research; Clinical Trials; Cohort Analysis; Consumption; Data; Databases; Diagnosis; Disease remission; Dose; Employee Strikes; Exercise; Food; Food Hypersensitivity; Fostering; General Hospitals; Goals; Health; Human; Hypersensitivity; IgE; Immune; Immune system; Immunologics; Immunology; Immunotherapy; Individual; Industry; Ingestion; Intervention; Intervention Studies; Intervention Trial; Leadership; Life; Massachusetts; National Institute of Allergy and Infectious Disease; Natural History; Oral; Outcome; Participant; Patients; Phase; Phase III Clinical Trials; Phenotype; Population; Population Study; Prevention; Production; Publishing; Randomized Controlled Trials; Reaction; Recruitment Activity; Reporting; Research; Research Infrastructure; Research Personnel; Resolution; Risk; Sampling; School-Age Population; Site; Spontaneous Remission; Testing; Therapeutic; Time; Toddler; Treatment Efficacy; Work; age related; career; clinical remission; clinically significant; cohort; desensitization; food antigen; high risk infant; industry partner; innovation; interest; operation; oral immunotherapy; primary outcome; response; skills

Oral immunotherapy (OIT) for peanut allergy has been the most studied interventional strategy for children with established allergy and is now the focus of an industry-sponsored phase 3 trial – one of the first in a field currently lacking any approved therapy. For the majority of patients treated, they can tolerate OIT adequately and it induces a substantial shift in the dose of allergen that elicits a reaction to a level well above most accidental ingestions, so long as they maintain consistent therapeutic exposure. This transient state of clinical protection, or `desensitization' as it is often referred to by allergists, is deemed an acceptable outcome by many patients, but there are limitations. For one, when in a desensitized state, unlike someone who is in true remission, there is some ongoing risk of treatment-associated reactions, especially with co-factors of inter-current illness, exercise, NSAID use, and others. Secondly, many patients find it very difficult to adhere to a chronic therapy. Therefore, even without the goal of ad lib peanut consumption, OIT would be a more beneficial intervention if efficacy were more durable and easier to maintain after an initial course of treatment. In fact, from several studies of children from school age and above, about 1/3 of patients do achieve a more durable benefit from OIT, defined by being able to avoid peanut for a month or more and remaining clinical tolerant to a clinically significant exposure. Those patients who achieve this more robust benefit tend to have lower peanut specific IgE levels at baseline, suggesting that there may be important immunological differences about them, but they are otherwise hard to identify. A just published study, however, suggests that young age at the time of OIT may also be associated with persistent tolerance after immunotherapy. This proposal would directly test the hypothesis that younger patients achieve OIT-induced tolerance at higher rates and would generate the clinical data and samples necessary to explore the immune mechanisms of age-dependent disparities.

花生过敏的口服免疫疗法(Oit)一直是研究最多的干预策略。 针对已确诊过敏的儿童，现在是行业赞助的3期试验的重点 -在目前缺乏任何批准的治疗方法的领域中，第一批之一。对于大多数患者来说 治疗后，他们可以充分耐受OIT，并诱导剂量发生实质性的变化 引起反应的过敏原的水平远远高于大多数意外摄入，只要它们 保持一致的治疗性暴露。这种短暂的临床保护状态，或 过敏症专科医生常说的“脱敏”，被认为是一个可接受的结果。 患者很多，但也有局限性。首先，当处于麻木状态时，不像某人 世卫组织处于真正缓解状态，存在治疗相关反应的持续风险， 特别是与间歇性疾病、运动、非甾体抗炎药的使用等共同因素。第二， 许多患者发现很难坚持长期治疗。因此，即使没有 随意食用花生的目标，如果有效率是 更耐用，在最初的疗程后更容易维护。事实上，从几个 对学龄儿童和以上儿童的研究表明，约三分之一的患者确实实现了更持久的 受益于OIT，定义为能够在一个月或更长时间内不吃花生，并保持 临床对临床重要暴露的耐受性。那些实现这一目标的患者更有活力 收益往往具有较低的花生特异性IgE水平，这表明可能存在 关于它们的重要免疫差异，但在其他方面很难识别。一场正义 然而，已发表的一项研究表明，OIT时的年轻也可能与此有关 免疫治疗后持续耐受。这一提议将直接检验这一假设 较年轻的患者以更高的耐受率获得OIT诱导的耐受性，并将产生 探讨年龄依赖性免疫机制所需的临床资料和标本 差距。